Depigoid Birch 5000 Longterm Study in Adults and Adolescents

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

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.

Study Overview

• Status: Completed
• Conditions: Allergic Rhinitis/Rhinoconjunctivitis +-Intermittent Asthma; Sensitization Against Betula Alba (Birch) Pollen
• Intervention / Treatment: Biological: s.c. injection

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 634
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13057
    • Hautarztpraxis
  • Bonn, Germany, 53105
    • Klinik und Poliklinik für Dermatologie und Allergologie der Universität

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 66 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Depigoid Birch 5.000 DPP/ml; 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)	Biological: s.c. injection; 3 years of therapy followed by 2 years (seasons) of treatment-free observational period; Other Names: Depigoid(R)Birch
Placebo Comparator: Placebo; 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)	Biological: s.c. injection; 3 years of therapy followed by 2 years (seasons) of treatment-free observational period; Other Names: Depigoid(R)Birch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proof of efficacy (superiority vs. placebo) by means of the combined Symptom and Medication Score (SMS).	For the primary outcome the SMS of nasal and ocular symptoms and their respective Rescue Medication score is used to assess efficacy of the perennial treatment regimen of Depigoid Birch 5000 DPP/mL versus placebo after 5 years (comprising 3 years of treatment plus 2 years treatment-free follow-up). An interim analysis will be conducted after 2 years. Data are captured via eDiary to be completed by the patients during each of the 5 pollen seasons within the duration of the study, starting prior to onset of pollen flight until after the end of the pollen seasons.	after 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom score (SS) during the 1st, 3rd, and 4th pollen seasons.	Differences between treatment groups also including pulmonary symptoms and for asthmatic/non-asthmatic patients. Data are captured via eDiary to be completed by the patients during each of the 5 pollen seasons within the duration of the study, starting prior to onset of pollen flight until after the end of the pollen seasons.	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).	Differences between treatment groups also including pulmonary symptoms and for asthmatic/non-asthmatic patients. Data are captured via eDiary to be completed by the patients during each of the 5 pollen seasons within the duration of the study, starting prior to onset of pollen flight until afte the end of the pollen seasons.	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.	Differences between treatment groups, during all 5 pollen seasons also including pulmonary symptoms and for asthmatic/non-asthmatic patients. Data are captured via eDiary to be completed by the patients during each of the 5 pollen seasons within the duration of the study, starting prior to onset of pollen flight until after the end of the pollen seasons.	after 1 year, 2 years, 3 years and 4 years
Rhinitis Quality of Life Questionnaire (RQLQ) resp. RQLQ for adolescent patients (AdolRQLQ)	Changes to baseline and difference between treatment groups during all 5 pollen seasons	Screening and after 1 year, 2 years, 3 years, 4 years and 5 years
Immunology parameters (Total IgE, specific IgE, specific IgG1 and IgG4)	Differences within patients and between treatment groups	Screening, after years 1, 2, 3 and 5 (resp. end of study)
Disease modifying effect after 5 years	Difference between treatment groups. Incidence of asthma and new sensitizations.	after 5 years
Clinical chemistry: Number of patients with outside range values	Differences between treatment groups	Screening, after years 2, 3 and 5
Adverse events: number of patients with AEs/SAEs	Including symptoms reported by patients in eDiary. Differences between treatment groups including but not limited to differences in severity levels of systemic reactions (SRs), immediate and local reaction including calculation of ratios per injection	throughout the whole study duration
Serum levels of Aluminium hydroxide (Pharmacokinetics)	Serum Aluminium hydroxide levels are assessed in a subgroup of 24 patients. Differences between treatment groups (adult patients only) Sampling: prior to 1st application of IMP, 4 time points after 1st, 2nd and 10th application (after 1 year). 24 hrs. urine at these 3 time points	prior and after 1st and 2nd application of IMP and after 1 year
Vitamin D3 level	Possible influence on specific immunotherapy. Exploratory evaluation	baseline and end of study
Hematology: Number of patients with outside range values	Differences between treatment groups	Screening, after years 2, 3 and 5

Collaborators and Investigators

• Sponsor: Leti Pharma GmbH
• Investigators: Principal Investigator: Natalja Novak, Prof. Dr., Klinik für Dermatologie und Allergologie der Universität Bonn; Study Director: Angelika Sager, Dr. med., LETI Pharma GmbH

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2012
• Primary Completion (Actual): July 30, 2018
• Study Completion (Actual): July 30, 2018

Study Registration Dates

• First Submitted: August 27, 2012
• First Submitted That Met QC Criteria: September 26, 2012
• First Posted (Estimate): September 27, 2012

Study Record Updates

• Last Update Posted (Actual): January 16, 2019
• Last Update Submitted That Met QC Criteria: January 15, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Immunotherapy; Allergic rhinitis; Hayfever; Allergic rhinoconjunctivitis; Allergy induced asthma; Birch (Betula alba)
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Eye Diseases; Bronchial Diseases; Otorhinolaryngologic Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Conjunctival Diseases; Asthma; Rhinitis; Rhinitis, Allergic; Conjunctivitis
• Other Study ID Numbers: 603-PG-PSC-191; 2012-000414-11 (EudraCT Number)