Dose Finding Study for Depigoid Birch: 4 Doses in Patients With Allergic Rhinitis/Rhinoconjunctivitis +-Asthma

This study has been completed.
Sponsor:
Collaborators:
Laboratorios LETI SL (Study Medication)
Pierrel Research Europe GmbH
Labor Dr. Spranger (Central lab)
Information provided by:
Leti Pharma GmbH
ClinicalTrials.gov Identifier:
NCT01144429
First received: June 10, 2010
Last updated: June 7, 2011
Last verified: June 2011
  Purpose

Specific immunotherapy for subcutaneous application: Dose finding study to evaluate the correct dose.

4 concentrations of a birch pollen allergen extract are applied in this study. Duration of therapy 20 weeks. Primary criterion is the Conjunctival Provocation Test (CPT), i.e. comparison between treatment arms of increased amount of quantities of allergen to provoke a positive CPT at the end of treatment.


Condition Intervention Phase
Allergic Rhinitis and/or Rhinoconjunctivitis +- Asthma
Immunotherapy, Allergen
Biological: Allergoid, allergenic extract of 100% Birch
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, DB, Parallel Group, MC Study to Evaluate the Efficacy and Safety of Four Doses of Depigmented Glutaraldehyde Polymerized Birch Pollen Allergenic Extract (Depigoid Birch) in Patients 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:
  • Conjunctival Provocation Test [ Time Frame: At screening and after approx 22 weeks (EoS) ] [ Designated as safety issue: No ]

    Comparison between dosage groups of percentage of patients who need an increased amount of allergen to provoke a positive CPT at the end of the treatment (comparison of slope of efficacy) It is expected that at the end of the study higher doses are necessary to provoke a positive CPT.

    Acc. to the EMEA "Guideline on clinical development of products for specific immunotherapy for the treatment of allergic diseases" provocation tests are accepted as primary outcomes for dose-finding studies.



Secondary Outcome Measures:
  • Laboratory parameters (immunology) [ Time Frame: At screening and after approx. 22 weeks (EoS) ] [ Designated as safety issue: No ]
    specific IgE (Birch), specific IgG1 and IgG4 (Birch). Comparison pre-post will be evaluated

  • Conjunctival Provocation Test [ Time Frame: after approx. 22 weeks ] [ Designated as safety issue: No ]
    Analysis of individual results for allergen amount

  • Laboratory (hematological, clinical chemistry, immunological) as a measure of safety [ Time Frame: At screening and after approx. 22 weeks (EoS) ] [ Designated as safety issue: Yes ]
    Clinically relevant changes need to be documented as AE. Comparison pre-post will be displayed descriptively.

  • Overall assessment of safety (tolerability)at the end of the study [ Time Frame: after approx. 22 weeks (EoS) ] [ Designated as safety issue: Yes ]

    At the end of the study investigator and patient will give their general overall impression on the safety of the study treatment on the following scale: excellent (no side effects at all), good (some minor local side effects), moderate (major local side effects or mild systemic side effects) or unaccaptable (anaphylactic reaction).

    Results will be compared between dosage groups


  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: at 4-weekly intervals (retrospectively at study visits) ] [ Designated as safety issue: Yes ]

    AEs are recorded at the study visits (patients are questioned and the patient diary - where allergy specific symptoms should be recorded by the patients during 48 hrs after each injection of IMP - is assessed by the investigator and AEs recorded in the CRF if applicable) and at any time of the study when site becomes aware of an AE/SAE.

    AE/SAE rate is compared between the treatment groups (safety profile). Also rates of local and systemic reactions will be calculated


  • Vital signs: Blood pressure and Heart rate as a measure of safety [ Time Frame: At screening and every study visit (4-weekly) ] [ Designated as safety issue: Yes ]
    Vital signs are measured a screening and every study visit. Clinically abnormal values must be assessed by the investigator and - if applicable - documented as AE. Vital signs will be evaluated descriptively

  • Patient diary: Allergy specific symptoms and concomitant medication (rescue m.) for 48 hrs after application of study medication [ Time Frame: 48 hrs every 4 weeks after each application of study medication ] [ Designated as safety issue: Yes ]

    Symptoms: urticaria, sneezing, runny nose, cough, dizziness, asthma symptoms, swelling/pain at the injection site.

    Symptoms documented in the diary will be judged and assessed by the investigator and transcribed as AE into the CRF if applicable Medication: Antihistaminics (Eye drops, nose spray), Sultanol, oral corticosteroids, other Intake of medication documented by the patients has to be transcribed to the CRF (Concomitant medication section)


  • Physical examination acc to local procedures as a measure of safety [ Time Frame: At screening and after approx. 22 weeks (EoS) ] [ Designated as safety issue: Yes ]
    A PE has to be performed at screening and end of study visit (22 weeks). Clinically abnormal findings must be assessed by the investigator and documented as AE if applicable. Data will be evaluated descriptively


Enrollment: 344
Study Start Date: June 2010
Study Completion Date: May 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 100 DPP/mL
Concentration of solution fo s.c. injection: 100 DPP/mL
Biological: Allergoid, allergenic extract of 100% Birch
Subcutaneous injections Build-up = 1 day: 0,1mL + 0,2mL + 0,2mL s.c. in intervals on 30 minutes; Maintenance = 5 x single injection of 0,5 mL s.c. every 4 weeks
Other Names:
  • Depigoid (R)
  • Depigmented, glutaraldehyd-polymerized allergenic extract of
Active Comparator: 1000 DPP/mL
Concentration of solution fo s.c. injection: 1000 DPP/mL
Biological: Allergoid, allergenic extract of 100% Birch
Subcutaneous injections Build-up = 1 day: 0,1mL + 0,2mL + 0,2mL s.c. in intervals on 30 minutes; Maintenance = 5 x single injection of 0,5 mL s.c. every 4 weeks
Other Names:
  • Depigoid (R)
  • Depigmented, glutaraldehyd-polymerized allergenic extract of
Active Comparator: 5000 DPP/mL
Concentration of solution fo s.c. injection: 5000 DPP/mL
Biological: Allergoid, allergenic extract of 100% Birch
Subcutaneous injections Build-up = 1 day: 0,1mL + 0,2mL + 0,2mL s.c. in intervals on 30 minutes; Maintenance = 5 x single injection of 0,5 mL s.c. every 4 weeks
Other Names:
  • Depigoid (R)
  • Depigmented, glutaraldehyd-polymerized allergenic extract of
Active Comparator: 10000 DPP/mL
Concentration of solution fo s.c. injection: 10000 DPP/mL
Biological: Allergoid, allergenic extract of 100% Birch
Subcutaneous injections Build-up = 1 day: 0,1mL + 0,2mL + 0,2mL s.c. in intervals on 30 minutes; Maintenance = 5 x single injection of 0,5 mL s.c. every 4 weeks
Other Names:
  • Depigoid (R)
  • Depigmented, glutaraldehyd-polymerized allergenic extract of

Detailed Description:

This is a dose finding study and no therapeutic study. Patients will receive in 4-weekly intervals 5x injections of 0,5 ml of a solution of modified birch pollen extract outside the pollen season. The primary endpoint therefore is not the therapeutic effect of the specific immunotherapy (effect on symptoms of allergy during the birch pollen season) but the effect on the CPT. Acc. to the EMEA "Guideline on clinical development of products for specific immunotherapy for the treatment of allergic diseases" provocation tests are accepted as primary outcomes for dose-finding studies.

For the CPT increasing doses of birch pollen solutions are applied to the eye and characteristic symptoms (eye redness, weeping, itching or burning and nose dripping/blockage) are assessed: 0 = absent, 1=mild, 2=moderate, 3=severe). At a score value of >= 5/concentration the test is considered positive and finished.

It is expected that at the end of the study higher doses are necessary to provoke a positive CPT.

Furthermore comparative evaluation of the safety data (AEs) in the different dosage groups is a very important parameter for the evaluation of the outcome of the study.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients have provided an appropriately signed and dated informed consent prior to any study specific examination,
  2. Patients must be ≥ 18 and ≤ 70 years of age at Visit 1,
  3. Patients must have a perception of disease activity of at least 30 mm on a 100 mm visual analogue scale (VAS),
  4. Patients must have an FEV1 or PEF value > 80% of the predicted normal value (for PEF: highest result of 3 measurements),
  5. Patients must complain about allergic rhinitis and/or rhinoconjunctivitis symptoms for at least 2 years with or without intermittent asthma symptoms, caused by clinical sensitization against birch pollen,
  6. IgE-mediated sensitization has to be verified by:

    • suggestive medical history, and
    • specific IgE against birch pollen (CAP-Rast ≥ 2), and
    • a positive SPT to birch pollen (the SPT is considered positive if it results in a wheal diameter of at least 3 mm and at least the size of histamine reference), and
    • a positive CPT with a birch pollen concentration of up to 10,000 SQ-units/mL.

    Special criteria for patients with co-allergies

  7. Patients do not suffer from typical symptoms against co-allergens,
  8. Specific CAP-RAST against co-allergens < CAP-RAST against birch pollen (the difference has to be ≥ 2), patients with co-allergens against animal dander can be randomized even if the CAP RAST difference is < 2, but must not be exposed to the specific allergen,
  9. Result of SPT against co-allergens < result of SPT against birch pollen.

Exclusion Criteria:

  1. Acute and chronic conjunctivitis,
  2. Infectious conjunctivitis,
  3. History of significant clinical manifestations of allergy as a result of sensitization against grass or weed pollen and perennial allergens (e.g. house dust mites),
  4. Symptoms due to co-allergies,
  5. Persistent asthma, according to the Global Initiative for Asthma (GINA) Guidelines,
  6. Acute or chronic inflammatory or infectious airway diseases including recurrent acute or chronic sinusitis,
  7. Chronic structural diseases of the lung (e.g. emphysema or bronchiectasis),
  8. Diseases of the immune system including autoimmune and immune deficiencies,
  9. Any disease, which prohibits the use of adrenaline (e.g. hyperthyroidism),
  10. Severe uncontrolled diseases that could increase the risk for the patients participating in the study, which include but are not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or hematological disorders,
  11. Any malignant disease during the previous 5 years,
  12. Any significant abnormal laboratory parameter or alteration in the vital signs that could increase the risk for the study patient,
  13. Alcohol, drug, or medication abuse within the past year,
  14. Severe psychiatric, psychological, or neurological disorders,
  15. Use of immunotherapy against birch pollen within the last 5 years,
  16. Topical and systemic treatment with β-blockers,
  17. Treatment with substances interfering with the immune system within 1 week prior to Visit 2,
  18. Use of tranquillizers or psychoactive drugs within 1 week prior to Visit 1,
  19. Use of systemic corticosteroids within 3 months prior to Visit 1,
  20. Immunization with vaccines within 7 days prior to Visit 2,
  21. Patients with hypersensitivity to excipients of the investigational medicinal product,
  22. Patients expected to be non-compliant and/or not co-operative,
  23. Exposure to any investigational drug within one month or 6 half lives,
  24. Patients who have already participated in this study,
  25. Patients who are employees of the institution, or 1st grade relatives, or partners of the investigator,
  26. Any donation of germ cells, blood, organs, or bone marrow during the course of the study,
  27. Patients who are not contractually capable,
  28. Nursing (lactating) women or a positive pregnancy test at Visit 1.
  29. Persons who are jurisdictional or governmentally institutionalized.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01144429

Locations
Germany
Dermatology Weber
Augsburg, Germany, 86163
Licca Klinik Dermatologie
Augsburg, Germany, 86179
Allergie-Centrum-Charité
Berlin, Germany, 10117
Klinische Froschung Berlin Mitte
Berlin, Germany, 10117
Hippke, Ear-Nose-Throat Specialist and Allergy
Berlin, Germany, 13057
Universität Bonn, Klinik und Poliklinik für Dermatologie
Bonn, Germany, 53127
Klinikum Carl-Gustav Carus, Klinik+Poliklinik für HNO
Dresden, Germany, 01307
Dominicus Hautzentrum
Duelmen, Germany, 48249
Spaeth, Ear-Nose-Throat Specialist and Allergy
Dueren, Germany, 52351
Thieme, Ear-Nose-Throat Specialist and Allergology
Duisburg, Germany, 47051
Klinische Forschung Hamburg GmbH
Hamburg, Germany, 20253
Clinical Research Hamburg GmbH
Hamburg, Germany, 22143
Stefan, Dermatology and Allergy
Hennef, Germany, 53773
Feussner, Pulmology and Allergology
Kassel, Germany, 34121
Tagesklinik für Allergie und Hautkrankheiten Brüning
Kiel, Germany, 24148
Medamed GmbH Studienambulanz
Leipzig, Germany, 04109
Zentrum für Therapiestudien der Innomed Leipzig GmbH
Leipzig, Germany, 04103
Amann, Ear-Nose-Throat Specialist and Allergy
Lingen, Germany, 49809
CRC Universitätsklinikum Mainz
Mainz, Germany, 55131
Universität, Klinik und Poliklinik für Hautkrankheiten
Muenster, Germany, 48149
Ear-Nose-Throat Specialist Schaefer
Pirna, Germany, 01796
Palm, Ear-Nose-Throat, Allergology
Roethenbach, Germany, 90552
Steinborn Dermatology
Straubing, Germany, 94315
Zentrum für Rhinologie und Allergie
Wiesbaden, Germany, 65183
Hautarztpraxis Allergie Hoffmann
Witten, Germany, 58453
Lithuania
Kaunas Medical University Clinics
Kaunas, Lithuania, 50009
Kaunas Distric Hospital
Kaunas, Lithuania, 45130
ENT Clinic "Trirema Medica"
Vilnius, Lithuania, 1113
Poland
Zakład Alergologii, SPZOZ Szpital Uniwersytecki w Krakowie
Krakow, Poland, 31531
NZOZ Centrum Alergologii
Lodz, Poland, 90553
Klinika Pulmonologii i Alergologii, SPZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. N. Barlickiego UM w Łodzi
Lodz, Poland, 90153
CSK UM w Łodzi, Klinika Immunologii, Reumatologii i Alergii, Zakład Immunologii Klinicznej
Lodz, Poland, 92213
Alergologia Plus, Specjalistyczny NZOZ, Ośrodek Diagnostyki i Terapii Uczuleń
Poznan, Poland, 60693
NZOZ Alergo-Med.
Poznan, Poland, 60823
Centrum Alergologii
Poznan, Poland, 60214
Alergo-Med. Specjalistyczna Przychodnia Lekarska Sp. z o. o.
Tarnow, Poland, 33100
Poradnia Alergologiczna, Gabinet Lekarski
Tomaszów Mazowiecki, Poland, 97200
NZOZ Almed Specjalistyczna Opieka Medyczna
Wroclaw, Poland, 50445
NZOZ Lekarze Specjaliści J. Małolepszy i Partnerzy
Wroclaw, Poland, 54239
Sponsors and Collaborators
Leti Pharma GmbH
Laboratorios LETI SL (Study Medication)
Pierrel Research Europe GmbH
Labor Dr. Spranger (Central lab)
Investigators
Principal Investigator: Margitta Worm, Prof. Dr. Charité Universitätsmedizin, Berlin, Germany
Study Chair: Angelika Sager, Dr. Leti Pharma GmbH, Witten, Germany
  More Information

No publications provided

Responsible Party: Dr. med. Angelika Sager, LETI Pharma GmbH
ClinicalTrials.gov Identifier: NCT01144429     History of Changes
Other Study ID Numbers: 603-PG-PSC-173, 2008-008448-26
Study First Received: June 10, 2010
Last Updated: June 7, 2011
Health Authority: Germany: Paul-Ehrlich-Institut
Lithuania: State Medicine Control Agency - Ministry of Health
Poland: Ministry of Health

Keywords provided by Leti Pharma GmbH:
Allergic Rhinitis +- intermittent asthma
Allergic Rhinoconjunctivitis +- intermittent asthma
Specific Immunotherapy

Additional relevant MeSH terms:
Asthma
Rhinitis
Conjunctivitis
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 April 21, 2014