A prospective, randomized, double-blind placebo-controlled multicentre study with mannan-conjugated birch pollen allergoids administered subcutaneously to adolescent and adult patients with birch pollen-induced allergic rhinitis or rhinoconjunctivitis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CCDRD Cooperative Clinical Drug Research and Development AG, Inmunotek S.L., ClinCompetence Cologne GmbH

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

26 Feb 2024 → 28 Jun 2024

Decision date (initial)

2024-02-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Inmunotek

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this trial is to assess the clinical impact of T502 treatment administered subcutaneously to participants with birch pollen-induced allergic rhinitis or rhinoconjunctivitis.

Conditions and MedDRA coding

Birch pollen induced allergic rhinitis or rhinoconjunctivitis

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed and dated Informed Consent Form a. by a legally competent participant, b. For adolescents: self-completed (signed and dated) participant informed consent to participate in the trial and signed and dated Informed Consent Form by both parents/legal guardian(s)
2. Patients aged from 12 to 64 years (at least 10% of the population should be 12-17 years of age (valid for Poland) OR patients aged from 18-64 years (valid for Germany)
3. Being in good physical and mental health
4. Confirmed normal renal and liver function, including non-clinically significant deviations outside the reference ranges (< grade 2 according to the FDA Guidance for Industry for preventive Vaccine Trials [FDA 2007] at screening visit. Participants with laboratory values > grade 1 will require retesting. Upon normalization of the outof- range value(s), the participant will be eligible)
5. Females with childbearing potential (a woman is considered of childbearing potential [WOCBP] according to the CTFG, if she is i.e., fertile, following menarche and until becoming postmenopausal unless becoming permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must be willing to use a highly effective method of contraception: a. Oral, intravaginal or transdermal hormonal medical drugs or -devices containing oestrogen/progesterone combinations. b. Oral, injectable or implantable hormonal medical drugs or -devices containing progesterone-only. c. Intrauterine device (IUD); d. Intrauterine hormone-releasing system (IUS) e. Bilateral tubal occlusion f. Vasectomized partner (provided that partner is the sole sexual partner of the WOCB trial participant and that the vasectomized partner has received medical assessment of the surgical success) g. Sexual abstinence (Defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant). or females unable to bear children (i.e., pre-menarche, tubal ligation, hysterectomy, or post-menopausal (a postmenopausal state is defined as no menses for 12 months without an alternative medical cause.)
6. Female participants with childbearing potential must have a negative pregnancy test in serum at screening
7. Having the diagnosis of birch pollen allergy based on all the following criteria: a. A medical history of moderate to severe allergic rhinitis or rhinoconjunctivitis for birch pollen allergens for at least 2 previous seasons (definition of allergy severity according to ARIA), b. A positive skin prick test (SPT - wheal diameter ≥3 mm) to birch pollen allergens, positive control (histamine) wheal ≥3 mm, negative control (NaCl) wheal <2 mm, c. Specific IgE against birch pollen allergens (minimum CAP class 3 or higher, ≥3.5 kU/L, in case that the IgE CAP-class is =2, the participant can be included, when a previous lab report [not older than 2 years and measurement outside the birch pollen season] states that the subject has CAP class 3 or higher), d. Being treated with anti-allergic medication for at least 2 seasons prior to enrolment
8. For asthmatic participants: confirmed diagnosis of controlled asthma during the treatment period according to Global Initiative for Asthma (GINA) guidelines (steps 1-3, GINA 2022)
9. FEV1 ≥80% of the participant’s reference value or Peak Expiratory Flow (PEF) ≥80% of the participants´ individual optimal value (for asthmatic participants only)

Exclusion criteria 33

1. Simultaneous participation in other clinical trials or previous participation within 30 days before inclusion
2. Previous immunotherapy with birch pollen allergens within the last 5 years
3. Ongoing immunotherapy with birch pollen allergens or any other allergens
4. Participants with acute allergic rhinitis or rhinoconjunctivitis due to other environmental allergens during the study period
5. Participants with a sensitization to other environmental allergens (i.e., house dust mites, cat dander, dog dander) and whose CAP class of the respective allergen specific IgE is higher than for birch pollen specific IgE
6. Being in any relationship or dependence with the Sponsor, CRO and/or Investigator
7. Inability to understand instructions/study documents
8. Participants who do not have access to a smartphone/tablet (iOS or Android, in exceptional cases, a paper diary may be issued if installation on the mobile device is not technically possible)
9. History of severe systemic reactions and/or anaphylaxis, including to food (e.g., peanut, marine animals) or to Hymenoptera venom (e.g., bee, wasp stings) or to medication (e.g., penicillin), etc.
10. Participants who have a suspected or symptoms of a SARS-COV-2 infection, who have had contact with a confirmed case of COVID-19 up to 3 days prior to the screening visit
11. History of hypersensitivity to the excipients of the investigational product or placebo
12. Mild persistent to severe persistent asthma, partly controlled or uncontrolled asthma according to GINA guidelines (GINA 2022) during the treatment period
13. Chronic asthma or emphysema, particularly with a Forced Expiratory Volume in 1 second (FEV1) <80% of the participant’s reference value (ECSC) or Peak Expiratory Flow (PEF) <80% of the participants’ individual optimal value
14. History of a respiratory tract infection and/or exacerbation of asthma within 4 weeks before the screening
15. History of significant renal disease or chronic hepatic disease
16. Malignant active disease (ongoing or within the five past years)
17. Severe autoimmune disease
18. Immune defects including immunosuppression, immunopathies
19. Vaccination during the entire treatment period, except flu and SARS-CoV-2 vaccinations
20. Use of systemic immunosuppressive medications (e.g., methotrexate or cyclosporine A) or blood transfusion from one month before screening until the end of the trial
21. General inflammatory, severe acute or chronic inflammatory diseases
22. Other chronic diseases such as severe congestive heart failure, cardiovascular insufficiency, active gastric ulcer, inflammatory bowel disease, uncontrolled diabetes mellitus, etc
23. Intake of antidepressant drugs with potent antihistamine properties such as tricyclic antidepressants (e.g., doxepin, amitriptyline, desipramine, imipramine, etc.)
24. Administration or planned administration of anti-IgE antibodies, mast cell stabilizers or anti-leukotriene agents
25. Intake of beta-blockers/ACE inhibitor medication (angiotensin-converting enzyme inhibitor)
26. Active tuberculosis
27. Having any contraindication for the use of adrenaline (including hyperthyroidism)
28. Known positive serology to Human Immunodeficiency Virus-1/2, Hepatitis B Virus or Hepatitis C Virus
29. Females who are pregnant, lactating, or of child-bearing potential and not using a highly effective contraceptive method
30. Administration of corticosteroids (systemicoral or nasal) or of anti-histaminic drugs within a defined time period preceding the trial (screening visit), as defined in the section Screening/Baseline Assessments and Proceduresnon-allowed drugs and procedures; exception made for routine (previously prescribed) control medication for asthmatic participants
31. Clinically relevant laboratory values, i.e., grade ≥2 according to the FDA Guidance for Industry for preventive Vaccine Trials (FDA 2007) at screening visit (Participants with laboratory values > grade 1 will require retesting. Upon normalization of the outof- range value(s), participant will be eligible)
32. Participants for who the Investigator believes will not comply with the study protocol (participants with known alcohol or drug abuse or with a history of a serious psychiatric disorder as well as participants unwilling to give informed consent or to abide by the requirements of the protocol)
33. Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The clinical impact of T502 treatment will be assessed by comparing the Combined Symptom and Medication Score (CSMS) over the peak birch pollen season 2024 between the placebo and the active treatment group.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CCDRD Cooperative Clinical Drug Research and Development AG

Sponsor organisation

CCDRD Cooperative Clinical Drug Research and Development AG

Address

Lindenallee 70, Dahlwitz-Hoppegarten Dahlwitz-Hoppegarten

City

Hoppegarten

Postcode

15366

Country

Germany

Scientific contact point

Organisation

Inmunotek S.L.

Contact name

Medical Director

Public contact point

Organisation

Inmunotek S.L.

Contact name

Medical Director

Inmunotek S.L.

Sponsor organisation

Inmunotek S.L.

Address

Calle Punto Mobi 5

City

Alcala De Henares

Postcode

28805

Country

Spain

ClinCompetence Cologne GmbH

Sponsor organisation

ClinCompetence Cologne GmbH

Address

Theodor-Heuss-Ring 14, Neustadt-Nord Neustadt-Nord

City

Cologne

Postcode

50668

Country

Germany

Sponsor responsibilities

Contact point sponsor

CCDRD Cooperative Clinical Drug Research and Development AG

Article 77 implementation

CCDRD Cooperative Clinical Drug Research and Development AG

Locations

2 EU/EEA countries · 54 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

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

Application history

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