Overview

This trial is active, not recruiting.

Conditions allergic rhinitis/rhinoconjunctivitis +-intermittent asthma, sensitization against betula alba (birch) pollen
Treatment s.c. injection
Phase phase 3
Sponsor Leti Pharma GmbH
Start date September 2012
End date May 2018
Trial size 634 participants
Trial identifier NCT01694836, 2012-000414-11, 603-PG-PSC-191

Summary

Specific immunotherapy for IgE mediated sensitization to birch pollen. Long-term study to assess safety and efficacy of Depigoid(R)Birch 5000 - a modified pollen extract of Betula alba (Birch) - versus placebo.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Suspension for s.c. injection. Treatment schedule: Build-up phase (1 day: 0,2 ml+0,3 ml at interval of 30 minutes) Maintenance phase (3 years: 0,5 ml at intervals of 4-6 weeks)
s.c. injection Depigoid(R)Birch
3 years of therapy followed by 2 years (seasons) of treatment-free observational period
(Placebo Comparator)
Suspension for s.c. injection. Treatment schedule: Build-up phase (1 day: 0,2 ml+0,3 ml at interval of 30 minutes) Maintenance phase (3 years: 0,5 ml at intervals of 4-6 weeks)
s.c. injection Depigoid(R)Birch
3 years of therapy followed by 2 years (seasons) of treatment-free observational period

Primary Outcomes

Measure
Proof of efficacy (superiority vs. placebo) by means of the combined Symptom and Medication Score (SMS).
time frame: after 5 years

Secondary Outcomes

Measure
Symptom score (SS) during the 1st, 3rd, and 4th pollen seasons.
time frame: after 1 year, 2 years, 3 years, 4 years and 5 years
Rescue Medication Score (RMS) during the 1st, 3rd, and 4th pollen season (futility and interim analyses).
time frame: after 1 year, 2 years, 3 years, 4 years and 5 years
combined Symptoms and Rescue Medication Score (SMS) during the 1st, 3rd, and 4th pollen season including pulmonary symptoms.
time frame: after 1 year, 2 years, 3 years and 4 years
Rhinitis Quality of Life Questionnaire (RQLQ) resp. RQLQ for adolescent patients (AdolRQLQ)
time frame: Screening and after 1 year, 2 years, 3 years, 4 years and 5 years
Immunology parameters (Total IgE, specific IgE, specific IgG1 and IgG4)
time frame: Screening, after years 1, 2, 3 and 5 (resp. end of study)
Disease modifying effect after 5 years
time frame: after 5 years
Clinical chemistry: Number of patients with outside range values
time frame: Screening, after years 2, 3 and 5
Adverse events: number of patients with AEs/SAEs
time frame: throughout the whole study duration
Serum levels of Aluminium hydroxide (Pharmacokinetics)
time frame: prior and after 1st and 2nd application of IMP and after 1 year
Vitamin D3 level
time frame: baseline and end of study
Hematology: Number of patients with outside range values
time frame: Screening, after years 2, 3 and 5

Eligibility Criteria

Male or female participants from 12 years up to 70 years old.

Inclusion Criteria: - Availability of an appropriately signed and dated informed consent before any study specific examination, - Clinical history of at least 2 years of seasonal allergic rhinitis and/or rhinoconjunctivitis with or without intermittent asthma due to birch pollen allergy that has required repeated use of symptomatic treatment, - Patients must have a minimum level of perception of symptoms from previous seasons defined as at least a moderate symptom level (i.e. a score of 2 on the 4-point-Likert scale) in at least 2 symptom categories prior to randomization, - Lung function ≥ 80% of the predicted normal value, - IgE-mediated sensitization has to be verified by: - suggestive medical history, and - specific IgE reactivity to birch pollen (CAP-RAST ≥ 2), and - a positive SPT to birch pollen at screening or within 1 months prior to the screening visit. An SPT is considered positive if it results in a wheal diameter of at least 3.0 mm - Internet access so that patients can complete the eDiary daily via internet during all 5 pollen seasons covered by the study protocol. Exclusion Criteria: - History of significant clinical manifestations of allergy as a result of sensitization against co-allergies, particularly—but not limited to—grass or weed pollen and perennial allergens (e.g. house dust mites, cat or dog). - History of anaphylactic reaction. - Moderate or severe persistent asthma (GINA 3 or 4). - Mild persistent asthma (GINA 2), according to the Global Initiative for Asthma Guidelines, necessitating treatment with inhaled glucocorticoids at a daily dose level of > 400 µg budesonide dose equivalents. - Lung function < 80% of the predicted normal value (for PEF: highest result of 3 measurements). - Acute or chronic inflammatory or infectious airway diseases including recurrent acute or chronic sinusitis. - Chronic structural diseases of the affected organs (e.g. eye, nose, lung). - History or presence of confirmed or potential diseases of the immune system including autoimmune diseases and immune deficiencies of actual clinical relevance. - Any disease that prohibits the use of adrenaline (e.g. hyperthyroidism). - Atopic dermatitis with SCORAD >30 in the past or at screening. - Ongoing or past full courses of SIT against birch pollen within the last 5 years. - Topical and systemic treatment with β-blockers. - Concomitant treatment with substances interfering with the immune system beginning 1 week prior to start of treatment. - Use of systemic corticosteroids within 3 months prior to Visit 1-1. - Immunization with vaccines within 7 days prior to Visit 1-1. - Treatment with antihistamines for any reason other than allergic symptoms due to birch pollen allergy. - Changed residence between geographical regions since the last birch pollen season or not staying in the geographical region during the pre-determined birch pollen season. - Nursing (lactating) women or women with a positive pregnancy test at the screening visit. Women of childbearing potential must be using highly effective contraception during participation in this clinical study. A highly effective method of birth control is defined as one that results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence, or vasectomised partner.

Additional Information

Official title Multicenter, Placebo-controlled, Long-term Study of Depigoid Birch 5000 in Adults and Adolescents With Allergic Rhinitis and/or Rhinoconjunctivitis With or Without Intermittent Asthma
Principal investigator Natalja Novak, Prof. Dr.
Description Investigation of the long-term efficacy and safety of Depigoid Birch 5000 according to the perennial treatment regimen in comparison to placebo in adult and adolescent patients with birch pollen-induced allergic rhinitis and/or rhinoconjunctivitis to show superiority vs. placebo. As the study includes adolescent patients it is run under an approved PIP. Total study duration per patient will be 5 years: 3 years of perennial treatment (application of study medication at intervals of 4-6 weeks) followed by a treatment-free observational phase of 2 years (seasons).
Trial information was received from ClinicalTrials.gov and was last updated in July 2014.
Information provided to ClinicalTrials.gov by Leti Pharma GmbH.