Phase II-III study to assess the efficacy and safety of subcutaneous cluster-immunotherapy in patients suffering from Olea europaea pollen allergy

Start 1 Sep 2024 · End 15 Oct 2025 · Status Ended · 1 EU/EEA countries · 6 sites · Protocol SC-3C2A

Overview

Sponsor-declared trial summary

Phase Phase II and Phase III (Integrated)

Status Ended

Participants planned 560

Countries 1

Sites 6

Moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to olive pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline

The purpose of this trial is to establish the most effective and best-tolerated dose of CLUSTOID®/CLUXIN® Olea europaea in terms of benefit-risk balance and CSMS (Combined Symptom and Medication Score).

Key facts

Sponsor: ROXALL Medizin GmbH
Participant type: Patients
Age range: 18-64 years
Gender: Male and Female
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Trial duration: 1 Sep 2024 → 15 Oct 2025
Decision date (initial): 2024-07-11
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: Roxall Medizin GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Dose response

Conditions and MedDRA coding

Moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to olive pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline

Version	Level	Code	Term	System organ class
20.0	LLT	10001728	Allergic rhinoconjunctivitis	10015919
20.0	LLT	10001726	Allergic rhinitis due to pollen	10021428

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

Patients who signed and dated the informed consent form obtained prior to any study-specific examination.
Female or male patients between 18 and 65 years of age at the time of signing the informed consent form
Patients with moderate-to-severe allergic rhinitis / rhinoconjunctivitis due to olive pollen for at least two years according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, either with well-controlled mild-to-moderate asthma defined in GINA guideline (Global Initiative for Asthma, 2023) or without asthma
Forced expiratory volume (FEV1) in one second > 80 % of predicted normal value (only for asthmatic patients).
Sensitization to Olea europaea pollen, verified by: positive skin prick test (wheal diameter ≥ 3 mm and negative control < 2 mm and positive (histamine) control ≥ 3 mm) and serum allergen-specific IgE to Olea europaea ≥ 0.7 kU/L (CAP EAST class ≥ 2) and a Retrospective Rhinoconjunctivitis Total Symptom Score (RRTSS) ≥ 2 (0-3 scale) based on the most severe days during one of the two OPS preceding enrolment and positive response to nasal provocation with either Olea europaea or cross-reactive Fraxinus excelsior pollen allergen extract (at least at the third concentration step)
Assumed compliance and ability of the patient to understand the patient’s electronic diary and to follow the instructions of the study staff.
Compliance and ability of the patient to complete an electronic diary for self-evaluation of the symptoms and rescue medication.
Safety laboratory results within the normal range or considered to be not clinically significant in any other case.

Exclusion criteria 34

Previous immunotherapy with Olea europaea or other pollen allergen extracts according to the homologous group of the “Oleaceae group”, as defined in Annex 1 in the Guideline on allergen products: production and quality issues (EMEA/CHMP/BWP/304831), within the last 5 years.
Patients with co-sensitizations or co-allergies to any perennial or seasonal allergen (with the exception of ash, privet and lilac tree for “Oleaceae group”), which interfere with the conduct of the study (e. g. with the tNPT or the CSMS recording), especially if the result in SPT for this allergen is higher than that for Olea europaea.
Patients with co-sensitizations to any mould or pollen with overlapping seasons but which are not cross-reactive with Olea europaea and, measured at the same time, with specific IgE levels ≥ class 2 CAP/PHADIA (unless the relevance can be excluded by component resolved diagnosis)
Simultaneous participation in other clinical trials.
Simultaneous specific immunotherapy with other allergens.
Participation, meaning randomization, in a trial in the last three months before enrolment.
Contraindications for SCIT (Pfaar et al., 2022; Pitsios et al., 2015)
Contraindications for SPT
Contraindications for NPT
Serious systemic reactions to allergen-specific immunotherapy in the past
Hypersensitivity to excipients of the IMP.
Any severe or unstable lung disease e. g. active tuberculosis, cystic fibrosis, COPD.
Severe, or partly controlled or uncontrolled asthma according to GINA guideline (Global Initiative for Asthma, 2023)
Asthmatic patients with FEV1 ≤ 80 % of predicted normal value at screening.
Chronic or severe acute diseases of nose or eyes.
Irreversible secondary disorders of the target organs (e. g. emphysema, bronchiectasis).
Therapy with immunoglobulins.
Completed or ongoing treatment with anti-IgE-antibody (like Omalizumab) and/or checkpoint-inhibitor.
Diseases of the immune system including autoimmune and immune deficiencies (with exception to well-controlled Hashimoto thyroiditis and type-1 diabetes mellitus).
Severe acute or chronic inflammatory or infectious diseases
Chronic or acute diseases of the heart, kidney or liver with severe impairment of their function.
Malignancy within the previous 5 years.
Active chronic urticaria.
Active severe atopic eczema.
Alcohol, drug, or medication abuse within the past year and/or during the study.
Existing or intended pregnancy, lactation or inadequate contraceptive measures for women with childbearing potential or a positive pregnancy test at screening.
Systemic and local (eye drops) treatment with beta-blockers.
Use of non-allowed medication.
Contraindication for adrenalin (for example, acute or chronic symptomatic coronary heart disease, severe hypertension, hyperthyroidism, glaucoma).
Severe psychiatric, psychological, or neurological disorders; completed or ongoing long-term treatment with tranquilizer or psychoactive drugs (including tricyclic anti-depressants).
Relationship or dependence with the sponsor and/or investigator.
Legal incapacity.
Patients who are jurisdictional or governmentally institutionalized.
Risk of non-compliance by the patient with the study procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

The primary (efficacy) endpoint is defined as the absolute difference in mean CSMS (Combined Symptom and Medication Score) during Peak Olive Pollen Period (POPP) of each active treatment group compared to the placebo treatment group.

Secondary endpoints 9

Absolute and relative differences in mean CSMS during OPS between active and placebo treatment groups.
Absolute and relative differences in mean dSS during POPP and OPS.
Absolute and relative differences in mean dMS during POPP and OPS.
Global Rhinoconjunctivitis Discomfort with a Visual Analogue Scale (VAS).
Change in Rhinoconjunctivitis quality of life questionnaire (RQLQ) between active and placebo treatment groups comparing basal and post-treatment scoring.
Well and severe days: A well day is defined as a day without administration of any rescue medication (dMS = 0) and with dSS < 0.34 (range 0-3). A severe day is defined (acc. to Pfaar et al. 2014) as a day with a single score = 3 in any of the six symptoms. Percentages of well and severe days will be calculated for each subject as the number of well or severe days in the POPP and OPS in relation to the number of days comprising both periods.
Symptom-free days are defined as the days with the absence of symptoms (dSS = 0) and without administration of any rescue medication (dMS = 0), expressed as percentage of days during the POPP and OPS
tNPT titrated Nasal Provocation Test: To assess the efficacy of each dose of CLU-RX-OLE compared to placebo. Defined as the percentage of patients with an increased dosing step and the change in the number of dosing steps needed to provoke a positive response in the titrated nasal provocation test (tNPT) post-treatment compared with pre-treatment (i. e. any improvement) in each of the four study groups
To analyse the safety and tolerability of each dose of CLU-RX-OLE compared to placebo by Treatment-Emergent Adverse Drug Reactions (TEADR) and patients affected with TEADRs in each group.

Investigational products

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

Test 3

CLU-RX-OLE mid dose

PRD11163106 · Product

Active substance: Allergenic Extract of Olea Europaea Pollen Polymerized with Glutaraldehyde
Substance synonyms: T517, Modified allergen extract of olive pollen polymerized with glutaraldehyde
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: TRANSDERMAL USE
Max daily dose: 0.7 ml millilitre(s)
Max total dose: 4.7 ml millilitre(s)
Max treatment duration: 48 Week(s)
Authorisation status: Not Authorised
ATC code: V01AA05 — TREE POLLEN
MA holder: ROXALL MEDIZIN GMBH
Paediatric formulation: No
Orphan designation: No

CLU-RX-OLE high dose

PRD11163107 · Product

Active substance: Allergenic Extract of Olea Europaea Pollen Polymerized with Glutaraldehyde
Substance synonyms: T517, Modified allergen extract of olive pollen polymerized with glutaraldehyde
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: TRANSDERMAL USE
Max daily dose: 0.7 ml millilitre(s)
Max total dose: 4.7 ml millilitre(s)
Max treatment duration: 48 Week(s)
Authorisation status: Not Authorised
ATC code: V01AA05 — TREE POLLEN
MA holder: ROXALL MEDIZIN GMBH
Paediatric formulation: No
Orphan designation: No

CLU-RX-OLE low dose

PRD11163105 · Product

Active substance: Allergenic Extract of Olea Europaea Pollen Polymerized with Glutaraldehyde
Substance synonyms: T517, Modified allergen extract of olive pollen polymerized with glutaraldehyde
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: TRANSDERMAL USE
Max daily dose: 0.7 ml millilitre(s)
Max total dose: 4.7 ml millilitre(s)
Max treatment duration: 48 Week(s)
Authorisation status: Not Authorised
ATC code: V01AA05 — TREE POLLEN
MA holder: ROXALL MEDIZIN GMBH
Paediatric formulation: No
Orphan designation: No