Depigoid Birch 5000 Longterm Study in Adults and Adolescents

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Leti Pharma GmbH
ClinicalTrials.gov Identifier:
NCT01694836
First received: August 27, 2012
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Allergic Rhinitis/Rhinoconjunctivitis +-Intermittent Asthma
Sensitization Against Betula Alba (Birch) Pollen
Biological: s.c. injection
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Leti Pharma GmbH:

Primary Outcome Measures:
  • Proof of efficacy (superiority vs. placebo) by means of the combined Symptom and Medication Score (SMS). [ Time Frame: after 5 years ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: No ]
    Changes to baseline and difference between treatment groups during all 5 pollen seasons

  • Immunology parameters (Total IgE, specific IgE, specific IgG1 and IgG4) [ Time Frame: Screening, after years 1, 2, 3 and 5 (resp. end of study) ] [ Designated as safety issue: No ]
    Differences within patients and between treatment groups

  • Disease modifying effect after 5 years [ Time Frame: after 5 years ] [ Designated as safety issue: No ]
    Difference between treatment groups. Incidence of asthma and new sensitizations.

  • Clinical chemistry: Number of patients with outside range values [ Time Frame: Screening, after years 2, 3 and 5 ] [ Designated as safety issue: Yes ]
    Differences between treatment groups

  • Adverse events: number of patients with AEs/SAEs [ Time Frame: throughout the whole study duration ] [ Designated as safety issue: Yes ]
    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

  • Serum levels of Aluminium hydroxide (Pharmacokinetics) [ Time Frame: prior and after 1st and 2nd application of IMP and after 1 year ] [ Designated as safety issue: Yes ]
    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

  • Vitamin D3 level [ Time Frame: baseline and end of study ] [ Designated as safety issue: No ]
    Possible influence on specific immunotherapy. Exploratory evaluation

  • Hematology: Number of patients with outside range values [ Time Frame: Screening, after years 2, 3 and 5 ] [ Designated as safety issue: Yes ]
    Differences between treatment groups


Enrollment: 634
Study Start Date: September 2012
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Depigoid Birch 5.000 DPP/ml

Suspension for s.c. injection. Treatment schedule:

  1. Build-up phase (1 day: 0,2 ml+0,3 ml at interval of 30 minutes)
  2. 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 Name: Depigoid(R)Birch
Placebo Comparator: Placebo

Suspension for s.c. injection. Treatment schedule:

  1. Build-up phase (1 day: 0,2 ml+0,3 ml at interval of 30 minutes)
  2. 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 Name: Depigoid(R)Birch

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

Ages Eligible for Study:   12 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01694836

Locations
Germany
Hautarztpraxis
Berlin, Germany, 13057
Klinik und Poliklinik für Dermatologie und Allergologie der Universität
Bonn, Germany, 53105
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Leti Pharma GmbH
ClinicalTrials.gov Identifier: NCT01694836     History of Changes
Other Study ID Numbers: 603-PG-PSC-191, 2012-000414-11
Study First Received: August 27, 2012
Last Updated: July 11, 2014
Health Authority: Germany: Paul-Ehrlich-Institut
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
Latvia: State Agency of Medicines
Lithuania: State Medicine Control Agency - Ministry of Health
Poland: National Institute of Medicines
Russia: The Ministry of Education and Science of the Russian Federation

Keywords provided by Leti Pharma GmbH:
Allergic rhinitis
Allergic rhinoconjunctivitis
Allergy induced asthma
Birch (Betula alba)
Hayfever
Immunotherapy

Additional relevant MeSH terms:
Asthma
Rhinitis
Conjunctivitis
Rhinitis, Allergic, Perennial
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Nose Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Conjunctival Diseases
Eye Diseases

ClinicalTrials.gov processed this record on August 21, 2014