Clinical trial NCT01694836: Depigoid Birch 5000 Longterm Study in Adults and Adolescents
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Allergic Rhinitis/Rhinoconjunctivitis +-Intermittent Asthma
Sensitization Against Betula Alba (Birch) Pollen
Keywords: Allergic rhinitis
Allergic rhinoconjunctivitis
Allergy induced asthma
Birch (Betula alba)
Hayfever
Immunotherapy
Lead sponsor: Leti Pharma GmbH
Sponsor class: INDUSTRY
First posted: 2012-09-27
Enrollment: 634
Sex: ALL
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Proof of efficacy (superiority vs. placebo) by means of the combined Symptom and Medication Score (SMS).
timeFrame: after 5 years
Secondary outcomes:
measure: Symptom score (SS) during the 1st, 3rd, and 4th pollen seasons.
timeFrame: after 1 year, 2 years, 3 years, 4 years and 5 years
measure: Rescue Medication Score (RMS) during the 1st, 3rd, and 4th pollen season (futility and interim analyses).
timeFrame: after 1 year, 2 years, 3 years, 4 years and 5 years
measure: combined Symptoms and Rescue Medication Score (SMS) during the 1st, 3rd, and 4th pollen season including pulmonary symptoms.
timeFrame: after 1 year, 2 years, 3 years and 4 years
measure: Rhinitis Quality of Life Questionnaire (RQLQ) resp. RQLQ for adolescent patients (AdolRQLQ)
timeFrame: Screening and after 1 year, 2 years, 3 years, 4 years and 5 years
measure: Immunology parameters (Total IgE, specific IgE, specific IgG1 and IgG4)
timeFrame: Screening, after years 1, 2, 3 and 5 (resp. end of study)
measure: Disease modifying effect after 5 years
timeFrame: after 5 years
measure: Clinical chemistry: Number of patients with outside range values
timeFrame: Screening, after years 2, 3 and 5
measure: Adverse events: number of patients with AEs/SAEs
timeFrame: throughout the whole study duration
measure: Serum levels of Aluminium hydroxide (Pharmacokinetics)
timeFrame: prior and after 1st and 2nd application of IMP and after 1 year
measure: Vitamin D3 level
timeFrame: baseline and end of study
measure: Hematology: Number of patients with outside range values
timeFrame: Screening, after years 2, 3 and 5
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Hautarztpraxis
city: Bonn
country: Germany
facility: Klinik und Poliklinik für Dermatologie und Allergologie der Universität
Study officials:
affiliation: Klinik für Dermatologie und Allergologie der Universität Bonn
name: Natalja Novak, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Leti Pharma GmbH
name: Angelika Sager, Dr. med.
role: STUDY_DIRECTOR
References: