Allergic Rhinitis/Rhinoconjunctivitis +-Intermittent AsthmaPhase 3NCT01694836
Depigoid Birch 5000 Longterm Study in Adults and Adolescents
A Phase 3 study testing s.c. injection in people with Allergic Rhinitis/Rhinoconjunctivitis +-Intermittent Asthma and Sensitization Against Betula Alba (Birch) Pollen, run by Leti Pharma GmbH at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 70 years
- Conditions the study is for
- Allergic Rhinitis/Rhinoconjunctivitis +-Intermittent Asthma, Sensitization Against Betula Alba (Birch) Pollen
- What is being tested?
- s.c. injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 634 participants
- Where
- 2 sitesGermany
- Study dates
- 17 Sep 2012to 30 Jul 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Hautarztpraxis
Berlin, 13057
Klinik und Poliklinik für Dermatologie und Allergologie der Universität
Bonn, 53105
About this study
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
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.
Read the 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).
- Conditions
- Allergic Rhinitis/Rhinoconjunctivitis +-Intermittent Asthma, Sensitization Against Betula Alba (Birch) Pollen
- Being tested
- s.c. injection
- Keywords
- Allergic rhinitis, Allergic rhinoconjunctivitis, Allergy induced asthma, Birch (Betula alba), Hayfever, Immunotherapy
- Medical subject headings
- Rhinitis, Allergic, Rhinitis, Allergic, Seasonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
s.c. injectionBiological
Also called Depigoid(R)Birch
3 years of therapy followed by 2 years (seasons) of treatment-free observational period
| Study group | Role | What they receive |
|---|---|---|
| Depigoid Birch 5.000 DPP/ml | Experimental | 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) Receives: Biological: s.c. injection |
| Placebo | Placebo comparator | 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) Receives: Biological: s.c. injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: after 5 years
Secondary outcomes (11)
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: after 5 years
Clinical chemistry: Number of patients with outside range values
Differences between treatment groups
Measured: 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
Measured: 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
Measured: prior and after 1st and 2nd application of IMP and after 1 year
Vitamin D3 level
Possible influence on specific immunotherapy. Exploratory evaluation
Measured: baseline and end of study
Hematology: Number of patients with outside range values
Differences between treatment groups
Measured: Screening, after years 2, 3 and 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2012 (estimated)
- Study start17 Sep 2012
- Primary completion30 Jul 2018
- Study completion30 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Allergic Rhinitis/Rhinoconjunctivitis +-Intermittent AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 634 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leti Pharma GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Natalja Novak, Prof. Dr., Principal investigator, Klinik für Dermatologie und Allergologie der Universität BonnAngelika Sager, Dr. med., Study director, Leti Pharma GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01694836
- Sponsor's protocol ID
- 603-PG-PSC-191
- Other IDs
- 2012-000414-11
- Status last verified
- Jan 2019
- First submitted
- 27 Aug 2012
- Last updated
- 16 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01694836
- Acronym / sponsor ID
- 603-PG-PSC-191
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 634 participants (actual)
- Lead sponsor
- Leti Pharma GmbHIndustry (pharma, biotech, devices)
- Study start
- 17 Sep 2012 (actual)
- Primary completion
- 30 Jul 2018 (actual)
- Study completion
- 30 Jul 2018 (actual)
- First posted
- 27 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Depigoid Birch 5.000 DPP/ml | Experimental | Biological: s.c. injectionSuspension 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) |
| Placebo | Placebo comparator | Biological: s.c. injectionSuspension 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) |
Who may qualify
- Ages
- 12 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (18 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| s.c. injectionAlso: Depigoid(R)Birch3 years of therapy followed by 2 years (seasons) of treatment-free observational period | Biological | Depigoid Birch 5.000 DPP/ml, Placebo |
Primary outcome
Proof of efficacy (superiority vs. placebo) by means of the combined Symptom and Medication Score (SMS).
Time frame: after 5 years
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.
11 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2019.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Natalja Novak, Prof. Dr. principal investigator
Klinik für Dermatologie und Allergologie der Universität Bonn
Angelika Sager, Dr. med. study director
Leti Pharma GmbH
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing s.c. injection in people with Allergic Rhinitis/Rhinoconjunctivitis +-Intermittent Asthma and Sensitization Against Betula Alba (Birch) Pollen, run by Leti Pharma GmbH at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proof of efficacy (superiority vs. placebo) by means of the combined Symptom and Medication Score (SMS). (time frame: after 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2019.