Clinical trial NCT01144429: Dose Finding Study for Depigoid Birch: 4 Doses in Patients With Allergic Rhinitis/Rhinoconjunctivitis +-Asthma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allergic Rhinitis and/or Rhinoconjunctivitis +- Asthma
Immunotherapy, Allergen
Keywords: Allergic Rhinitis +- intermittent asthma
Allergic Rhinoconjunctivitis +- intermittent asthma
Specific Immunotherapy
Lead sponsor: Leti Pharma GmbH
Sponsor class: INDUSTRY
Collaborators: name: Laboratorios LETI SL (Study Medication)
name: Pierrel Research Europe GmbH
name: Labor Dr. Spranger (Central lab)
First posted: 2010-06-15
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Conjunctival Provocation Test
timeFrame: At screening and after approx 22 weeks (EoS)
Secondary outcomes:
measure: Laboratory parameters (immunology)
timeFrame: At screening and after approx. 22 weeks (EoS)
measure: Conjunctival Provocation Test
timeFrame: after approx. 22 weeks
measure: Laboratory (hematological, clinical chemistry, immunological) as a measure of safety
timeFrame: At screening and after approx. 22 weeks (EoS)
measure: Overall assessment of safety (tolerability)at the end of the study
timeFrame: after approx. 22 weeks (EoS)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: at 4-weekly intervals (retrospectively at study visits)
measure: Vital signs: Blood pressure and Heart rate as a measure of safety
timeFrame: At screening and every study visit (4-weekly)
measure: Patient diary: Allergy specific symptoms and concomitant medication (rescue m.) for 48 hrs after application of study medication
timeFrame: 48 hrs every 4 weeks after each application of study medication
measure: Physical examination acc to local procedures as a measure of safety
timeFrame: At screening and after approx. 22 weeks (EoS)
Other outcomes:
Locations:
city: Augsburg
country: Germany
facility: Dermatology Weber
city: Augsburg
country: Germany
facility: Licca Klinik Dermatologie
city: Berlin
country: Germany
facility: Allergie-Centrum-Charité
city: Berlin
country: Germany
facility: Klinische Froschung Berlin Mitte
city: Berlin
country: Germany
facility: Hippke, Ear-Nose-Throat Specialist and Allergy
city: Bonn
country: Germany
facility: Universität Bonn, Klinik und Poliklinik für Dermatologie
city: Dresden
country: Germany
facility: Klinikum Carl-Gustav Carus, Klinik+Poliklinik für HNO
city: Duelmen
country: Germany
facility: Dominicus Hautzentrum
city: Dueren
country: Germany
facility: Spaeth, Ear-Nose-Throat Specialist and Allergy
city: Duisburg
country: Germany
facility: Thieme, Ear-Nose-Throat Specialist and Allergology
city: Hamburg
country: Germany
facility: Klinische Forschung Hamburg GmbH
city: Hamburg
country: Germany
facility: Clinical Research Hamburg GmbH
city: Hennef
country: Germany
facility: Stefan, Dermatology and Allergy
city: Kassel
country: Germany
facility: Feussner, Pulmology and Allergology
city: Kiel
country: Germany
facility: Tagesklinik für Allergie und Hautkrankheiten Brüning
city: Leipzig
country: Germany
facility: Zentrum für Therapiestudien der Innomed Leipzig GmbH
city: Leipzig
country: Germany
facility: Medamed GmbH Studienambulanz
city: Lingen
country: Germany
facility: Amann, Ear-Nose-Throat Specialist and Allergy
city: Mainz
country: Germany
facility: CRC Universitätsklinikum Mainz
city: Muenster
country: Germany
facility: Universität, Klinik und Poliklinik für Hautkrankheiten
city: Pirna
country: Germany
facility: Ear-Nose-Throat Specialist Schaefer
city: Roethenbach
country: Germany
facility: Palm, Ear-Nose-Throat, Allergology
city: Straubing
country: Germany
facility: Steinborn Dermatology
city: Wiesbaden
country: Germany
facility: Zentrum für Rhinologie und Allergie
city: Witten
country: Germany
facility: Hautarztpraxis Allergie Hoffmann
city: Kaunas
country: Lithuania
facility: Kaunas Distric Hospital
city: Kaunas
country: Lithuania
facility: Kaunas Medical University Clinics
city: Vilnius
country: Lithuania
facility: ENT Clinic "Trirema Medica"
city: Krakow
country: Poland
facility: Zakład Alergologii, SPZOZ Szpital Uniwersytecki w Krakowie
city: Lodz
country: Poland
facility: Klinika Pulmonologii i Alergologii, SPZOZ Uniwersytecki Szpital Kliniczny Nr 1 im. N. Barlickiego UM w Łodzi
city: Lodz
country: Poland
facility: NZOZ Centrum Alergologii
city: Lodz
country: Poland
facility: CSK UM w Łodzi, Klinika Immunologii, Reumatologii i Alergii, Zakład Immunologii Klinicznej
city: Poznan
country: Poland
facility: Centrum Alergologii
city: Poznan
country: Poland
facility: Alergologia Plus, Specjalistyczny NZOZ, Ośrodek Diagnostyki i Terapii Uczuleń
city: Poznan
country: Poland
facility: NZOZ Alergo-Med.
city: Tarnow
country: Poland
facility: Alergo-Med. Specjalistyczna Przychodnia Lekarska Sp. z o. o.
city: Tomaszów Mazowiecki
country: Poland
facility: Poradnia Alergologiczna, Gabinet Lekarski
city: Wroclaw
country: Poland
facility: NZOZ Almed Specjalistyczna Opieka Medyczna
city: Wroclaw
country: Poland
facility: NZOZ Lekarze Specjaliści J. Małolepszy i Partnerzy
Study officials:
affiliation: Charite University, Berlin, Germany
name: Margitta Worm, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Leti Pharma GmbH, Witten, Germany
name: Angelika Sager, Dr.
role: STUDY_CHAIR
References: