Moderate to Severe… · Phase III (2023-504942-75-01)

Start 22 Aug 2024 · End 30 Mar 2026 · Status Ended · 6 EU/EEA countries · 73 sites · Protocol PM/0059

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ended

Participants planned 582

Countries 6

Sites 73

Moderate to Severe Allergic Rhinitis/Rhinoconjunctivitis with or without Asthma Induced by House Dust Mite (HDM) Allergy

To assess clinical efficacy of PM Mixture 50,000 AUeq/mL (0.5 mL) SCIT in subjects suffering from moderate to severe HDM-induced ARC, measured by difference in the average Total Combined Rhinitis Score (TCRS) during the last 8 weeks of one (± 1 month) year treatment, between PM treatment and placebo. Each symptom will …

Key facts

Sponsor: HAL Allergy B.V.
Participant type: Patients
Age range: 18-64 years
Gender: Male and Female
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Trial duration: 22 Aug 2024 → 30 Mar 2026
Decision date (initial): 2024-09-22
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: HA Allergy B.V.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Secondary objectives 8

To assess the effect of PM treatment by comparing the average daily Total Nasal Symptom Score (TNSS) between PM and placebo during the last 8 weeks of one (± 1 month) year treatment of subjects with HDM-allergic ARC.
To assess the effect of PM treatment by comparing the average daily Rhinitis Medication Score (RMS) between PM and placebo during the last 8 weeks of one (± 1 month) year treatment of subjects with HDM-allergic ARC.
To assess the effect of PM treatment, by comparing the average Total Combined Conjunctivitis Score (TCCS) between PM and placebo, during the last 8 weeks of the one (± 1 month) year treatment of subjects with HDM-allergic ARC.
To assess difference of change from baseline in Nasal Provocation Test (NPT) at the end of study compared to baseline, between PM and placebo treatment groups.
To assess immunological effects by comparing the change from baseline to the end of treatment of immunoglobulin levels E, G and G4 (IgE, IgG, IgG4) against D. pter and D. far, between PM and placebo treatment groups.
To assess Rhinoconjunctivitis Quality of Life Questionnaire - RQLQ(S) after the treatment, between PM and placebo treatment groups.
To evaluate safety and tolerability of PM treatment versus placebo during the entire treatment period as assessed by treatment-related adverse events, local and systemic reactions, clinical and laboratory parameters.
To assess the safety of PM treatment versus placebo on asthma parameters e.g. asthma related concomitant medication, asthma related adverse events and lung function tests.

Conditions and MedDRA coding

Moderate to Severe Allergic Rhinitis/Rhinoconjunctivitis with or without Asthma Induced by House Dust Mite (HDM) Allergy

Version	Level	Code	Term	System organ class
20.0	LLT	10001728	Allergic rhinoconjunctivitis	10015919
21.1	LLT	10001724	Allergic rhinitis (excl hay fever)	10038738

Study design 3 periods

#	Title	Allocation	Blinding	Roles blinded	Arms
1	Screening Before any screening activities are performed, subjects will provide written informed consent. Prior to randomization, the eligibility of the subjects will be confirmed by an allergic medical history to HDM minimum 1 year; positive SPT for HDM D. pter or D. far; allergen-specific serum IgE to D. pter or D. far of at least class 2 (>0.7 U/mL); a positive NPT for D. pter (Lebel score ≥6 at 10,000 AU/mL); a minimum FEV1 of >70% predicted and an average baseline TNSS of at least 8 points out of 12. During screening period the electronic diary will be completed for 28 days, out of which last 14 days will be used to calculate the average baseline TNSS score. The screening period will have a duration of 28-42 days, depending on the time required for the wash-out of Rescue Medication (see schedule of events).	Not Applicable	None
2	Up-dosing The up-dosing visits will take place when eligibility has been confirmed and the patient can be randomized.	Randomised Controlled	Double	[{"id":174090,"code":1,"name":"Subject"},{"id":174089,"code":2,"name":"Investigator"}]	Purethal Mites: Purethal Mites Placebo: Placebo
3	Maintenance After 6 weekly (±3 days) up-dosing injections (with a maximum of 4 additional injections, if required per protocol), the first maintenance injection M1 will be scheduled 2 weeks (±5 days) after the last up-dosing visit, followed by other 2 injections (M2-M3) with 2-week (±5 days) interval. Maintenance visits 4-13 (M4-M13) will take place on a 4-week basis (±7 days) after M3. Total treatment period should be within 52 weeks. In case of additional up-dosing visits and/or dose delays, M4 can be scheduled with 2-week interval and M13 can be skipped (see the Protocol for details).	Randomised Controlled	Double	[{"id":174093,"code":2,"name":"Investigator"},{"id":174092,"code":1,"name":"Subject"}]	Purethal Mites: Purethal Mites Placebo: Placebo

Regulatory references

Scientific advice from competent authorities: Paul-Ehrlich-Institut
EMA paediatric investigation plan (PIP): EMEA-000902-PIP01-10
Plan to share IPD: No

EU CT number	Title	Sponsor
2023-504942-75-00	A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Study to Assess the Efficacy of PURETHAL Mites Mixture 50,000 AUeq/mL Subcutaneous Immunotherapy in Adult Subjects with Moderate to Severe Allergic Rhinitis/Rhinoconjunctivitis with or without Asthma Induced by House Dust Mite (HDM) Allergy	HAL Allergy B.V.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

Prior to screening, subjects need to have signed the current approved Informed Consent Form (ICF).
Male or female subjects age 18-65 years at the time of informed consent.
Clinical history consistent with moderate-severe HDM allergic rhinitis (with or without asthma) according to the ARIA classification (Allergic Rhinitis and its Impact on Asthma) (Bousquet et al., 2008), for at least one year prior to the first dosing.
Subjects should be able and willing to complete daily e-Diaries for a period of 4 weeks during the screening period, 1 week after maintenance visit 7, and for a period of 8 weeks at the end of treatment under the same living conditions.
Forced Expiratory Volume 1 (FEV1) > 70% at Screening.
If a subject is asthmatic, asthma must be controlled during the entire trial. (corresponding to GINA treatment steps 1 or 2). Subjects with seasonal allergy may be included, if they allow to control asthma only with short-acting beta2- agonists and/or dose inhaled corticosteroid (≤400mcg budesonide or equivalent) during TCRS scoring periods.
Positive SPT to D. pter and/or D. far (mean wheal diameter ≥ 3 mm, negative control should be < 2 mm, histamine positive control should be ≥ 3 mm), assessed at Screening.
Subjects with a positive NPT for D. pter extract at Screening (Lebel score ≥6 at 10,000 AU/mL, test should be postponed, if baseline score is ≥ 3 or if negative control score is > 3).
Allergen specific serum IgE level for D. pter and/or D. far of > 0.7 U/mL, assessed at Screening.
Subjects need to have an average daily TNSS of at least 8 out of 12 points at baseline, determined according to the daily e-Diary entries during 2 weeks of baseline assessment. Subjects should have a minimum e-Diary entry compliance of 70% for which the average is calculated.
Negative serum pregnancy test at screening for women of childbearing potential.
Females of childbearing potential must be using 2 effective methods of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the trial..

Exclusion criteria 25

A clinically relevant history of symptomatic seasonal ARC and/or a positive SPT (mean wheal diameter ≥ 3 mm) caused by an allergen (including animal hair and dander), to which the subject is regularly exposed and/or exposure is overlapping with the e-Diary completion periods at Screening and at the end of treatment.
Nasal surgery and/or severe nasal or severe oral disease within 6 months prior to Screening.
Patients not adhering to the e-Diary procedure and/or procedure for Rescue Medication use during e-Diary phase.
Moderate and severe asthma (GINA 2022 treatment steps 3 - 5).
Uncontrolled asthma, as defined by any of the following: a. Asthma Control Test (ACT) ≤19, b. FEV1 ≤70% of predicted value, c. Emergency room visit for asthma attack/exacerbation within 6 months prior to screening, d. At least 1 hospitalization due to asthma within the last year, History of intubation/mechanical ventilation due to asthma, f. More than 2 courses of oral steroids used for treatment of asthma within the last 6 months prior to Screening, g. Daily use of inhaled corticosteroids >400mcg budesonide or equivalent.
History of anaphylaxis with cardio-respiratory symptoms (food allergy, drugs or an idiopathic reaction).
Previous treatment with AIT with HDM allergen or a cross-reacting allergen for more than 1 month at the maintenance level within the last 5 years. Initiation of HDM SCIT is acceptable, if treatment has been discontinued before reaching maintenance dose.
AIT (subcutaneous, sublingual or oral) with other allergens than HDM within the last 3 months prior to screening or planned during the trial period.
Participation in a clinical trial within the last 3 months prior to screening (e.g. new investigational drug or biological) or during the trial.
Any vaccination (including COVID-19) less than 1 week prior to screening, during screening and the up-dosing phase and the TCRS scoring periods.
Any immunosuppressive treatment or anti-IgE therapy within the last 6 months prior to the first dosing of the trial drug and during the trial.
Severe immune disorders (including autoimmune diseases) and/or diseases requiring immunosuppressive medication.
Active COVID-19 infection at the time of screening or 2 weeks before.
Active malignancies or any malignant disease in the last 5 years.
A chronic or acute disease that in the opinion of the investigator might place the subject at an additional risk, including but not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, haematological disorders, severe atopic dermatitis, other relevant skin diseases (affecting SPT testing areas).
Diseases with a contraindication for the use of adrenaline/epinephrine (e.g. hyperthyroidism, glaucoma).
Use of prohibited medication and/or not able to discontinue medications that are prohibited during the specified trial periods.
Moderate to severe nasal obstructive disease such as polyps, septum deviation.
Clinically significant chronic sinusitis or ocular infection.
Female subjects of childbearing potential who are pregnant or lactating.
Alcohol, drug, or medication abuse within the past year and during the trial.
Any (expected) lack of cooperation or compliance upon the discretion of the investigator.
Severe psychiatric, psychological, or neurological disorders.
Employees, 1st degree relatives, or partners of the investigator.
Expected changes in average HDM exposure during the trial (e.g. new avoidance measures, relocation and holidays or trips lasting more than 10 days during the efficacy assessment period)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Average daily TCRS during the last 8 weeks of treatment.

Secondary endpoints 8

Average daily TNSS during the last 8 weeks of treatment.
Average daily RMS during the last 8 weeks of treatment.
Average daily TCCS during the last 8 weeks of treatment.
Change from baseline in NPT (Lebel score) at the end of treatment.
Change from baseline in IgE, IgG, IgG4 levels against D. pter and D. far at the end of treatment.
RQLQ(S) at the end of treatment.
Safety and tolerability during the entire treatment period assessed by treatment-related adverse events, local and systemic reactions.
Safety of the treatment on asthma parameters assessed by asthma-related concomitant medication use, asthma related adverse events and lung function tests.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

PURETHAL Mites 50.000 AUeq/mL

PRD3979312 · Product

Active substance: Dermatophagoides Pteronyssinus
Pharmaceutical form: SUSPENSION FOR INJECTION
Route of administration: SUBCUTANEOUS USE
Max daily dose: 0.5 ml millilitre(s)
Max total dose: 8.05 ml millilitre(s)
Max treatment duration: 52 Week(s)
Authorisation status: Not Authorised
ATC code: V01AA03 — HOUSE DUST
MA holder: HAL ALLERGY B.V.
Paediatric formulation: No
Orphan designation: No

Placebo 4

Phenol

SUB12552MIG · Substance

Active substance: Phenol
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS USE
Max daily dose: 2.5 mg milligram(s)
Max total dose: 40.25 mg milligram(s)
Max treatment duration: 52 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Water for Injection

SUB12398MIG · Substance

Active substance: Water for Injection
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS USE
Max daily dose: 0.5 ml millilitre(s)
Max total dose: 8.05 ml millilitre(s)
Max treatment duration: 52 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sodium Chloride

SUB12581MIG · Substance

Active substance: Sodium Chloride
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS USE
Max daily dose: 4.5 mg milligram(s)
Max total dose: 72.45 mg milligram(s)
Max treatment duration: 52 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Aluminium Hydroxide

SUB33625 · Substance

Active substance: Aluminium Hydroxide
Pharmaceutical form: SUSPENSION FOR INJECTION
Route of administration: SUBCUTANEOUS USE
Max daily dose: 0.45 mg milligram(s)
Max total dose: 7.24 mg milligram(s)
Max treatment duration: 52 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Auxiliary 15

Loratadine

SUB08581MIG · Substance

Active substance: Loratadine
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 10 mg milligram(s)
Max total dose: 4200 mg milligram(s)
Max treatment duration: 60 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

PRICK TEST Beifuss LETI, 30 HEP/ml Pricktestlösung.

PRD625124 · Product

Active substance: Artemisia Vulgaris Pollen Extract
Substance synonyms: MUGWORT POLLEN EXTRACT
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Week(s)
Authorisation status: Authorised
ATC code: V04CL — TESTS FOR ALLERGIC DISEASES
Marketing authorisation: PEI.D.02488.01.1
MA holder: LETI PHARMA GMBH
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Azelastine

SUB05649MIG · Substance

Active substance: Azelastine
Pharmaceutical form: EYE DROPS
Route of administration: OCULAR USE
Max daily dose: 0.06 mg milligram(s)
Max total dose: 42 mg milligram(s)
Max treatment duration: 60 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Mometasone

SUB09045MIG · Substance

Active substance: Mometasone
Pharmaceutical form: NASAL SPRAY, SUSPENSION
Route of administration: NASAL USE
Max daily dose: 200 µg microgram(s)
Max total dose: 84 mg milligram(s)
Max treatment duration: 60 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Prick Test Gemeiner Beifuß

PRD630667 · Product

Active substance: Artemisia Vulgaris
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V01AA02 — GRASS POLLEN
Marketing authorisation: 1307A/89N
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Pricktest Negativkontrolle, Pricktestlösung

PRD6866428 · Product

Active substance: Phenol, Liquefied
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V04CL — TESTS FOR ALLERGIC DISEASES
Marketing authorisation: PEI.D.11973.01.1
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Prick Test Hausstaubmilbe Dermatophagoides Pteronyssinus

PRD648010 · Product

Active substance: Dermatophagoides Pteronyssinus
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V01AA03 — HOUSE DUST
Marketing authorisation: 1403A/89N
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Prick Test Hausstaubmilbe Dermatophagoides Farinae

PRD648011 · Product

Active substance: Dermatophagoides Farinae
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V01AA03 — HOUSE DUST
Marketing authorisation: 1404A/89N
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Prick Test Aspergillus Fumigatus

PRD630694 · Product

Active substance: Aspergillus Fumigatus
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V01AA04 — MOULD FUNGUS AND YEAST FUNGUS
Marketing authorisation: 1357A/89N
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Prick Test Positieve Controle 10 mg/ml, oplossing voor huidpriktest

PRD493640 · Product

Active substance: Histamine Dihydrochloride
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V04CL — TESTS FOR ALLERGIC DISEASES
Marketing authorisation: RVG 16820
MA holder: HAL ALLERGY BENELUX B.V.
MA country: Netherlands
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Prick Test Frühblühende Bäume Mischung I

PRD630679 · Product

Active substance: Corylus Avellana L.
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V01AA05 — TREE POLLEN
Marketing authorisation: 1338A/89N
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Prick Test Katzenepithelien

PRD630688 · Product

Active substance: Cat Epithelia
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V01AA11 — ANIMALS
Marketing authorisation: 1437A/89N
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Prick Test Hundeepithelien

PRD630687 · Product

Active substance: Dog Epithelia
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V01AA11 — ANIMALS
Marketing authorisation: 1436A/89N
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Prick Test Gräserpollen-Mischung

PRD648013 · Product

Active substance: Phleum Pratense
Substance synonyms: TIMOTHY
Pharmaceutical form: SOLUTION FOR SKIN-PRICK TEST
Route of administration: CUTANEOUS USE
Max daily dose: 1 Gtt drop(s)
Max total dose: 1 Gtt drop(s)
Max treatment duration: 1 Day(s)
Authorisation status: Authorised
ATC code: V01AA02 — GRASS POLLEN
Marketing authorisation: 760A/89N
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

HAL Allergy Provo Spray, Provokationstestlösung, Nasenspray

PRD671730 · Product

Active substance: Dermatophagoides Pteronyssinus
Pharmaceutical form: SOLUTION FOR PROVOCATION TEST
Route of administration: NASAL USE
Max daily dose: 0.18 ml millilitre(s)
Max total dose: 0.54 ml millilitre(s)
Max treatment duration: 3 Day(s)
Authorisation status: Authorised
ATC code: V04CL — TESTS FOR ALLERGIC DISEASES
Marketing authorisation: 1403A/89NB-2
MA holder: HAL ALLERGY B.V.
MA country: Germany
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

HAL Allergy B.V.

Sponsor organisation: HAL Allergy B.V.
Address: J.h. Oortweg 15-17
City: Leiden
Postcode: 2333 CH
Country: Netherlands

Scientific contact point

Organisation: HAL Allergy B.V.
Contact name: Hans Hoogeveen

Public contact point

Organisation: HAL Allergy B.V.
Contact name: Hans Hoogeveen MSc. PhD.

Locations

6 EU/EEA countries · 73 investigational sites

By country

Country	MS status	Planned subjects	Sites
Austria	Ended	30	2
Bulgaria	Ended	83	6
Germany	Ended	149	20
Latvia	Ended	22	2
Lithuania	Ended	22	7
Poland	Ended	276	36
Rest of world	—	0	—

Investigational sites

Austria

2 sites · Ended

Ordensklinikum Linz GmbH

Dermatology, Fadingerstrasse 1, 4020, Linz

Ordensklinikum Linz GmbH

Otorhinolaryngology, Head and Neck Surgery, Seilerstaette 4, 4010, Linz

Bulgaria

6 sites · Ended

Medical Center Smolyan OOD

Allergology, Bulevard Bilgariya 2, 4700, Smolyan

Medical Center Prolet EOOD

Allergologist, Ulitsa Olimpi Panov 25, 7000, Ruse

Alexandrovska University Hospital

Clinic of Allergology, Georgy Sofiiski Str 1, 1431, Sofia

Diagnostic Consultative Centre Ascendent EOOD

Ear, Nose, Throat, Ulitsa Bacho Kiro 47, 1202, Sofia

Diagnostics And Consultation Center Convex Ltd.

NA, Ulitsa Sinanishko Ezero 11a, 1680, Sofiya

University Multiprofile Hospital For Active Treatment Kaspela EOOD

Clinic of Ear Nose and Throat Diseases, Zapaden District, Sofia Str 64, Plovdiv

Germany

20 sites · Ended

Allergie- und Asthma-Studienzentrum

Allergology, Karl-Carstens-Straße 11, 53113, Bonn

Klinische Forschung Osnabrueck

Dermatology, Hakenstrasse 1, Innenstadt, Osnabrueck

Klinikum Stuttgart, Klinik fur Dermatologie and Allergologie, Allergieabteilung, Ambulanz 3

Allergology, Priessnitzweg 24, 70374, Stuttgart

Medizentrum Essen Borbeck

Allergology, Huelsmannstrasse 6, Borbeck, Essen

FutureMeds GmbH

Allergology, Wilmersdorfer Strasse 79, Charlottenburg, Berlin

Allergo GmbH, Prüfzentrum Schorndorf

Allergology, Welzheimer Str.15, 73614, Schorndorf

Berufsausuebungsgemeinschaft Bag Prof. Dr. Med Gerhard Hoheisel Dr. Med Andreas Bonitz GbR

Allergology, Holzhaeuser Strasse 78a, Stoetteritz, Leipzig

HNO Praxis Dreieich

Allergology, Heckenweg 3, 63303, Dreieich

Ballenberger, Freytag, Wenisch

Allergology, Robert-Koch-Str. 1, 63263, Neu-Isenburg

Technische Universitat Dresden

Otorhinolaryngology, Fetscherstrasse 74, Johannstadt-Nord, Dresden

Facharzt für Hals-Nasen-Ohrenheilkunde, Allergologie ambulante u. stationäre Operationen

Allergology, Markt 18, 09648, Mittweida

Pneumologisches Forschungsinstitut Hohegeest GbR

Allergology, Bohnenstr. 1, 21502, Geesthacht

Studienzentrum Dr. med. Schlenska

Allergology, Duttenstedter Str. 13a, 31224, Peine

HNO Praxis Göttingen

Allergology, Friedrichstr. 3-4, 37073, Göttingen

HNO Praxis Dr. Thieme

Allergology, Mercatorstraße 10-12, 47051, Duisburg

HNO Praxis Dr. Sonja Runge

Allergology, Rosa-Luxemburg-Damm 1, 15366, Neuenhagen

Praxis für HNO und Allergologie

Allergology, Overbeckstr 33, 01139, Dresden

HNO Praxis Dresden Dr. med. Udo Schäfer

Allergology, Altmarkt 10A, 01067, Dresden

HNO research GmbH

Alergology, Sandkuhle 17, 25524, Itzehoe

Studienzentrum Dr. Laßmann

Allergology, Obere Straße 18-20, 07318, Saalfeld

Latvia

2 sites · Ended

Mediciniska sabiedriba ALERGISKO SLIMIBU IZMEKLESANAS UN ARSTESANAS CENTRS SIA

Center of the investigation in treatment of allergic disease, Firsa Sadovnikova Iela 20, LV-1003, Riga

LOR Klinika

NA, Vienibas Gatve 51, 1004, Riga

Lithuania

7 sites · Ended

Alerginiu Susirgimu Diagnostikos Ir Gydymo Centras UAB

Department of Immunology and Allergology, Seliu G. 64, Vilniaus M. Sav., Vilnius

Inovatyvios alergologijos centras UAB

NA, M. Mazvydo G. 13-47, Vilniaus M. Sav., Vilnius

Lietuvos sveikatos mokslu universiteto ligonine Kauno klinikos

Department of Immunology and Allergology, Eiveniu G. 2, Kauno M. Sav., Kaunas

Inlita UAB

NA, Santariskiu G. 5, Vilniaus M. Sav., Vilnius

CD8 klinika UAB

Clinic of Immunology and Allergology, Jonavos G. 7, Kauno M. Sav., Kaunas

Verkiu klinika UAB

Clinic of Immunology and Allergology, Apkasu G. 6-7, Vilniaus M. Sav., Vilnius

Seimos Gydytojas UAB

NA, Pylimo G. 9, Vilniaus M. Sav., Vilnius

Poland

36 sites · Ended

Alergo-Med Specjalistyczna Przychodnia Lekarska Sp. z o.o.

not applicable, Pck 26 Street, 33-100, Tarnow

Centrum Medyczne Kermed Renata Bijata-Bronisz I Ewa Kowalinska Sp. j.

Not Applicable, Ul. Krolowej Jadwigi 16, 85-231, Bydgoszcz

Indywidualna Specjalistyczna Praktyka Lekarska Elżbieta Matusz

no applicable, ul. Klonowa 4, 72-300, Gryfice

Centrum Diagnostyczno Terapeutyczne Medicus Sp. z o.o.

Not Applicable, Ul. Lesna 8, 59-300, Lubin

Centrum Alergologii Sp. z o.o.

cetrum Allergologii, Ul. Kawaleryjska 10, 20-552, Lublin

Pro Life Medica Sp. z o.o.

ETG lublin, Ul. Wladyslawa Kunickiego 26a, 20-412, Lublin

Krakowskie Centrum Medyczne Sp. z o.o.

Not Applicable, Ul. Mikolaja Kopernika 32 St, 31-501, Cracow

Provita Sp. z o.o.

otolaryngology, Ul. Fabryczna 15b, 40-611, Katowice

Etg Warszawa Sp. z o.o.

ETG warszawa, Ul. Wynalazek 4, 02-677, Warsaw

Specjalistyczna Praktyka Lekarska AlerMedica Teresa Piotrowska

not applicable, ul. Mlynowa 38 U5/6, 15-404, Bialystok

Centrum Alergologii Teresa Hofman Sp. z o.o.

Allergology, Ul. Wojciecha Boguslawskiego 16a, 60-214, Poznan

Uniwersytecki Szpital Kliniczny Nr 1 Im Norberta Barlickiego Uniwersytetu Medycznego W Lodzi SPZOZ

poradnia Alergologiczna, Ul. Dr Stefana Kopcinskiego 22, 90-153, Lodz

Niepubliczny Zaklad Opieki Zdrowotnej Centrum Uslug Medycznych Proximum Sp. z o.o.

Allergologay, Ul. Zelazna 34, 53-428, Wroclaw

Indywidualna Specjalistyczna Praktyka Lekarska Elżbieta Murawska-Waliszewska

Not Applicable, ul. Feliksa Nowowiejskiego 7, 75-587, Koszalin

Centrum Medyczne Lucyna Andrzej Dymek

Not Applicable, ul. Parafialna 1, 47-100, Strzelce Opolskie

Gabinet Lekarski Bożena Kubicka-Kozik Poradnia Alergologiczna

not applicable, ul. Juliusza Słowackiego 22, 97-200, Tomaszów Mazowiecki

ALL-MED - Specjalistyczna Opieka Medyczna - Medyczny Instytut Badawczy

not applicable, al. Gen. Józefa Hallera 95, 53-201, Wrocław

Uniwersytecki Szpital Kliniczny Nr 4 W Lublinie

Not Applicable, Ul. Dra Kazimierza Jaczewskiego 8, 20-090, Lublin

Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o.o.

not applicable, Plac Szczepanski 3, 31-011, Cracow

Malopolskie Centrum Alergologii Sp. z o.o.

out patient clinic, Osiedle Piastow 40, 31-624, Cracow

Homeo Medicus Szczesiul sp.j.

Not Applicable, Ul. Komisji Edukacji Narodowej 3b Lok. 1, 15-687, Bialystok

Clinica Vitae Sp. z o.o.

Department of pulmonology and allergology, Ul. Gospody 7, 80-344, Gdansk

Pratia S.A.

Not Applicable, Ul. 3 Maja 16, 42-217, Czestochowa

Specjalistyczna Przychodnia Lekarska Alergo Med Sp. z o.o.

not applicable, Ul Mieczyslawa Niedzialkowskiego 10a/50, 61-578, Poznan

IRMED Irena Wojciechowska

not applicable, ul. Eustachego Tyszkiewicza 13 lok.U1, Poland, Warsaw

Indywidualna Specjalistyczna Praktyka Lekarska Jan Zdanowski Specjalista Alergolog

not applicable, ul. Heleny Modrzejewskiej 2/2, 75-729, Koszalin

Alergotest s.c. Specjalistyczne Centrum Medyczne

Not Applicable, ul. Jana Sapiehy 2/4A, 20-095, Lublin

Specjalistyczna Praktyka Lekarska Dr. n. med. Joanna Orlicz-Widawska

Not Applicable, ul. Korczaka 10, 40-338, Katowice

Polimedica Centrum Badan Profilaktyki I Leczenia Sp. z o.o.

Not Applicable, Aleja Komisji Edukacji Narodowej 98/u17, 02-777, Warsaw

Niepubliczny Specjalistyczny Zaklad Opieki Zdrowotnej Puls-Med Anna Bogusz Agnieszka Musielak Sp. j.

not applicable, Ul. 1 Maja 55, 26-110, Skarzysko-Kamienna

Ip Clinic Sp. z o.o.

not applicable, Ul. Gen. Lucjana Zeligowskiego 3/5, 90-752, Lodz

Santa Sp. z o.o.

Not Applicable, Pilota Stanislawa Wigury 19, 90-302, Lodz

Poradnie Specjalistyczne Alergologia Plus Justyna Rakowicz

Not Applicable, ul. Drobnika 12/14, 60-693, Poznan

Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny Anna Płoszczuk

not applicable, ul. Przejazd 2a, 15-430, Białystok

Velocity Skierniewice Sp. z o.o.

Not Applicable, Ul. Ogrodowa 21/23, 96-100, Skierniewice

Pzu Zdrowie S.A.

poradnia Alergologiczna, Ul. Ignacego Paderewskiego 4b, 25-017, Kielce

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Trial end	Recruitment start	Recruitment end
Austria	2024-12-13		2025-01-20	2025-01-29
Bulgaria	2024-08-22	2026-03-18	2024-10-09	2025-01-29
Germany	2024-08-22	2026-03-30	2024-09-09	2025-01-29
Latvia	2024-08-22	2026-03-23	2024-09-17	2025-01-29
Lithuania	2024-08-22	2026-03-25	2024-09-11	2025-01-29
Poland	2024-08-22	2026-03-24	2024-09-09	2025-01-29

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 114 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Type	Title	Version
Protocol (for publication)	D1_Protocol_2023-504942-75-01_redacted	3.1
Recruitment arrangements (for publication)	K1_Description of the procedure for involving subjects in the study_LTU	NA
Recruitment arrangements (for publication)	K1_Recruitment and IC Procedure_AUT	1
Recruitment arrangements (for publication)	K1_Recruitment and IC Procedure_BGR	1
Recruitment arrangements (for publication)	K1_Recruitment and IC Procedure_BGR	1
Recruitment arrangements (for publication)	K1_Recruitment and IC Procedure_LTU	2
Recruitment arrangements (for publication)	K1_Recruitment and IC Procedure_LVA	1
Recruitment arrangements (for publication)	K1_Recruitment and Informed consent procedure	3.0
Recruitment arrangements (for publication)	K1_Recruitment and Informed consent procedure_POL	NA
Recruitment arrangements (for publication)	K1_Recruitment Material_Newspaper Advertisement	1
Recruitment arrangements (for publication)	K1_Site 59-123_Recruitment Material_Newspaper Advertisement	2.0
Recruitment arrangements (for publication)	K2_Advertisement_HalAllergy website_EN	1.2
Recruitment arrangements (for publication)	K2_Advertisement_HalAllergy website_LT	1.2
Recruitment arrangements (for publication)	K2_Advertisement_Newspaper Ad_BGR	1
Recruitment arrangements (for publication)	K2_Advertisement_Newspaper Ad_LTU	1.1
Recruitment arrangements (for publication)	K2_Advertisement_Newspaper Ad_LVA	1
Recruitment arrangements (for publication)	K2_Advertisement_Newspaper Ad_RUS	1
Recruitment arrangements (for publication)	K2_PM0059_Newspaper Ad_pl	1
Recruitment arrangements (for publication)	K2_Recruitment Material_Advertisment_HAL Website_AUT	1.0
Recruitment arrangements (for publication)	K2_Recruitment Material_Advertisment_HAL Website_BGR	1
Recruitment arrangements (for publication)	K2_Recruitment Material_Advertisment_HAL Website_BGR-bul	1
Recruitment arrangements (for publication)	K2_Recruitment Material_Advertisment_HAL Website_LVA	1
Recruitment arrangements (for publication)	K2_Recruitment Material_Newspaper Advertisement_AUT	1.o
Recruitment arrangements (for publication)	K2_Recruitment Material_Studienproband_AUT	2.1
Recruitment arrangements (for publication)	K2_site 59-126_Studienproband_Recruitment material_Advertisement	2
Recruitment arrangements (for publication)	K2_Site 59-137_Recruitment Material_Advertisement	1.3
Recruitment arrangements (for publication)	K2_Site 59-139_Recruitment Material_Advertisement	1.0
Recruitment arrangements (for publication)	K2_Sponsor Website Advertisement text	1.0
Recruitment arrangements (for publication)	K2_Sponsor Website Advertisment text	1.0
Recruitment arrangements (for publication)	K2_Studienproband_Recruitment material_Advertisement	2.0
Recruitment arrangements (for publication)	K2_Studienproband_Recruitment material_Advertisement_tracked changes	2.0
Subject information and informed consent form (for publication)	L1 Patient information and Informed consent document	3.1
Subject information and informed consent form (for publication)	L1_List of Contact for participating sites_AUT	NA
Subject information and informed consent form (for publication)	L1_PM0059_POL_SIS and ICF adults_pl_clean	3.3
Subject information and informed consent form (for publication)	L1_SIS and ICF_BGR	3.1
Subject information and informed consent form (for publication)	L1_SIS and ICF_BGR_20230906_Eng	1.2
Subject information and informed consent form (for publication)	L1_SIS and ICF_LTU	3.2
Subject information and informed consent form (for publication)	L1_SIS and ICF_LVA	3.1
Subject information and informed consent form (for publication)	L1_SIS and ICF_Main_AUT	3.3
Subject information and informed consent form (for publication)	L1_SIS and ICF_Master_20230523_Eng	1.1
Subject information and informed consent form (for publication)	L1_SIS and ICF_PP_AUT	1.3
Subject information and informed consent form (for publication)	L1_SIS and ICF_RUS	3.1
Subject information and informed consent form (for publication)	L2 GP Letter	1.1
Subject information and informed consent form (for publication)	L2 Participant Card	1.1
Subject information and informed consent form (for publication)	L2 patient diary Email Alerts	2.0
Subject information and informed consent form (for publication)	L2 patient diary Email Alerts	2.0
Subject information and informed consent form (for publication)	L2 patient diary Injection Symptoms	2.0
Subject information and informed consent form (for publication)	L2 patient diary Injection Symptoms	2.0
Subject information and informed consent form (for publication)	L2 patient diary Nasal and Eye Symptoms	2.0
Subject information and informed consent form (for publication)	L2 patient diary Nasal and Eye Symptoms	2
Subject information and informed consent form (for publication)	L2 patient diary Quality of Life	1
Subject information and informed consent form (for publication)	L2 patient diary Quality of Life	1
Subject information and informed consent form (for publication)	L2 patient diary Reference Form	2.0
Subject information and informed consent form (for publication)	L2 patient diary Reference Form	2.0
Subject information and informed consent form (for publication)	L2 Questionnaire_Asthma Control Test	1
Subject information and informed consent form (for publication)	L2 Questionnaire_Asthma Control Test_AUT	1
Subject information and informed consent form (for publication)	L2_GP Letter_AUT	2.0
Subject information and informed consent form (for publication)	L2_GP letter_BGR	1
Subject information and informed consent form (for publication)	L2_GP letter_LTU	1
Subject information and informed consent form (for publication)	L2_GP letter_LVA	1
Subject information and informed consent form (for publication)	L2_Participant Card_AUT	2.0
Subject information and informed consent form (for publication)	L2_Patient card_BGR	2.0
Subject information and informed consent form (for publication)	L2_Patient card_LTU	2
Subject information and informed consent form (for publication)	L2_Patient card_LTU_tc	2
Subject information and informed consent form (for publication)	L2_Patient card_LVA	2.0
Subject information and informed consent form (for publication)	L2_Patient card_RUS	2.0
Subject information and informed consent form (for publication)	L2_patient diary Email Alerts	2.0
Subject information and informed consent form (for publication)	L2_Patient Diary Email Alerts_AUT	2
Subject information and informed consent form (for publication)	L2_Patient diary Email Alerts_LTU	2
Subject information and informed consent form (for publication)	L2_patient diary Email Alerts_pl	2.0
Subject information and informed consent form (for publication)	L2_Patient Diary Injection Symptoms_AUT	2
Subject information and informed consent form (for publication)	L2_patient diary Injection Symptoms_LTU	2
Subject information and informed consent form (for publication)	L2_patient diary Injection Symptoms_LVA	2.0
Subject information and informed consent form (for publication)	L2_patient diary Injection Symptoms_pl	2.0
Subject information and informed consent form (for publication)	L2_patient diary Injection Symptoms_RUS	2.0
Subject information and informed consent form (for publication)	L2_Patient Diary Nasal and Eye Symptoms_AUT	2.0
Subject information and informed consent form (for publication)	L2_patient diary Nasal and Eye Symptoms_LTU	2
Subject information and informed consent form (for publication)	L2_patient diary Nasal and Eye Symptoms_LVA	2
Subject information and informed consent form (for publication)	L2_patient diary Nasal and Eye Symptoms_pl	2.0
Subject information and informed consent form (for publication)	L2_patient diary Nasal and Eye Symptoms_RUS	2
Subject information and informed consent form (for publication)	L2_Patient Diary Quality of Life_AUT	1.0
Subject information and informed consent form (for publication)	L2_patient diary Quality of Life_LTU	1
Subject information and informed consent form (for publication)	L2_patient diary Quality of Life_LVA	1
Subject information and informed consent form (for publication)	L2_patient diary Quality of Life_RUS	1
Subject information and informed consent form (for publication)	L2_Patient Diary Reference Form_AUT	2
Subject information and informed consent form (for publication)	L2_patient diary Reference Form_LTU	2
Subject information and informed consent form (for publication)	L2_patient diary Reference Form_LVA	2.0
Subject information and informed consent form (for publication)	L2_patient diary Reference Form_pl	2.0
Subject information and informed consent form (for publication)	L2_patient diary Reference Form_RUS	2.0
Subject information and informed consent form (for publication)	L2_patient diary_Quality of Life_pl	1
Subject information and informed consent form (for publication)	L2_Patient Information Rescue Medication	1.0
Subject information and informed consent form (for publication)	L2_Patient Information_LTU_Rescue Medication	1.1
Subject information and informed consent form (for publication)	L2_PM0059 Patient card_pl	2.0
Subject information and informed consent form (for publication)	L2_PM0059 Patient card_pl_tracked changes	2.0
Subject information and informed consent form (for publication)	L2_PM0059_GP letter_pl	1
Subject information and informed consent form (for publication)	L2_Poland Astma Control Test_pl	1
Subject information and informed consent form (for publication)	L2_Questionnaire ACT_LTU	1
Subject information and informed consent form (for publication)	L2_Questionnaire ACT_LVA	1
Subject information and informed consent form (for publication)	L2_Questionnaire ACT_RUS	1
Subject information and informed consent form (for publication)	L2_Questionnaire_ACT_BGR	1
Subject information and informed consent form (for publication)	L2_Rescue Medication	1.0
Subject information and informed consent form (for publication)	L2_Rescue Medication_DEU	1.0
Subject information and informed consent form (for publication)	L2_Rescue Medication_POL	1.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis_layperson_BG_2023-504942-75-01	2.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_layperson_EN_2023-504942-75-01	2.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_layperson_LT_2023-504942-75-01	2.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_layperson_LV_2023-504942-75-01	2.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_layperson_PL_2023-504942-75-01	2.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_scientific_BG_2023-504942-75-01	3.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_scientific_DE_2023-504942-75-01	3.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_scientific_EN_2023-504942-75-01	3.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_scientific_LT_2023-504942-75-01	3.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_scientific_LV_2023-504942-75-01	3.1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_scientific_PL_2023-504942-75-01	3.1

Application history

32 submissions — initial application plus substantial / non-substantial modifications

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2023-10-24	Germany	Acceptable 2024-01-11	2024-01-11
2	NON SUBSTANTIAL MODIFICATION	NSM-1	2024-01-11	Germany	Acceptable 2024-01-11	2024-01-11
3	SUBSTANTIAL MODIFICATION	SM-2	2024-03-14	Germany	Acceptable 2024-05-13	2024-05-14
4	NON SUBSTANTIAL MODIFICATION	NSM-2	2024-06-12	Germany	Acceptable 2024-05-13	2024-06-12
5	SUBSTANTIAL MODIFICATION	SM-3	2024-06-26		Acceptable	2024-08-07
6	SUBSTANTIAL MODIFICATION	SM-4	2024-06-26	Germany	Acceptable	2024-08-08
7	SUBSTANTIAL MODIFICATION	SM-5	2024-06-26		Acceptable	2024-09-16
8	SUBSTANTIAL MODIFICATION	SM-6	2024-06-26		Acceptable	2024-09-23
9	SUBSTANTIAL MODIFICATION	SM-7	2024-06-26		Acceptable	2024-08-02
10	SUBSEQUENT ADDITION OF MSC	APP-10	2024-06-26		Acceptable 2024-05-13	2024-09-22
11	NON SUBSTANTIAL MODIFICATION	NSM-5	2024-10-03	Germany	Acceptable 2024-05-13	2024-10-03
12	NON SUBSTANTIAL MODIFICATION	NSM-6	2024-10-15	Germany	Acceptable 2024-05-13	2024-10-15
13	SUBSTANTIAL MODIFICATION	SM-12	2024-10-18	Germany	Acceptable	2024-11-18
14	SUBSTANTIAL MODIFICATION	SM-11	2024-10-23		Acceptable	2024-12-10
15	SUBSTANTIAL MODIFICATION	SM-14	2024-10-23		Acceptable	2025-01-14
16	SUBSTANTIAL MODIFICATION	SM-15	2024-10-24		Acceptable	2025-01-15
17	SUBSTANTIAL MODIFICATION	SM-13	2024-10-29		Acceptable	2025-01-16
18	SUBSTANTIAL MODIFICATION	SM-16	2024-11-04		Acceptable	2025-02-10
19	NON SUBSTANTIAL MODIFICATION	NSM-9	2025-02-18			2025-02-18
20	NON SUBSTANTIAL MODIFICATION	NSM-10	2025-02-18	Germany		2025-02-18
21	NON SUBSTANTIAL MODIFICATION	NSM-11	2025-02-19			2025-02-19
22	NON SUBSTANTIAL MODIFICATION	NSM-12	2025-02-19	Germany		2025-02-19
23	NON SUBSTANTIAL MODIFICATION	NSM-13	2025-02-25	Germany		2025-02-25
24	NON SUBSTANTIAL MODIFICATION	NSM-15	2025-02-27			2025-02-27
25	SUBSTANTIAL MODIFICATION	SM-17	2025-04-18		Acceptable	2025-05-30
26	SUBSTANTIAL MODIFICATION	SM-18	2025-04-18	Germany	Acceptable	2025-05-20
27	SUBSTANTIAL MODIFICATION	SM-19	2025-04-18		Acceptable	2025-06-30
28	SUBSTANTIAL MODIFICATION	SM-20	2025-04-18		Acceptable	2025-05-28
29	NON SUBSTANTIAL MODIFICATION	NSM-16	2025-07-30	Germany	Acceptable	2025-07-30
30	SUBSTANTIAL MODIFICATION	SM-22	2025-08-08	Germany	Acceptable 2025-11-17	2025-11-18
31	NON SUBSTANTIAL MODIFICATION	NSM-17	2025-12-16	Germany	Acceptable 2025-11-17	2025-12-16
32	SUBSTANTIAL MODIFICATION	SM-23	2026-02-27	Germany	Acceptable	2026-04-29