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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 344
- 试验地点
- 78
- 主要终点
- Conjunctival Provocation Test
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients have provided an appropriately signed and dated informed consent prior to any study specific examination,
- •Patients must be ≥ 18 and ≤ 70 years of age at Visit 1,
- •Patients must have a perception of disease activity of at least 30 mm on a 100 mm visual analogue scale (VAS),
- •Patients must have an FEV1 or PEF value > 80% of the predicted normal value (for PEF: highest result of 3 measurements),
- •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,
- •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
- •Patients do not suffer from typical symptoms against co-allergens,
- •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,
- •Result of SPT against co-allergens < result of SPT against birch pollen.
排除标准
- •Acute and chronic conjunctivitis,
- •Infectious conjunctivitis,
- •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),
- •Symptoms due to co-allergies,
- •Persistent asthma, according to the Global Initiative for Asthma (GINA) Guidelines,
- •Acute or chronic inflammatory or infectious airway diseases including recurrent acute or chronic sinusitis,
- •Chronic structural diseases of the lung (e.g. emphysema or bronchiectasis),
- •Diseases of the immune system including autoimmune and immune deficiencies,
- •Any disease, which prohibits the use of adrenaline (e.g. hyperthyroidism),
- •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,
- •Any malignant disease during the previous 5 years,
- •Any significant abnormal laboratory parameter or alteration in the vital signs that could increase the risk for the study patient,
- •Alcohol, drug, or medication abuse within the past year,
- •Severe psychiatric, psychological, or neurological disorders,
- •Use of immunotherapy against birch pollen within the last 5 years,
- •Topical and systemic treatment with β-blockers,
- •Treatment with substances interfering with the immune system within 1 week prior to Visit 2,
- •Use of tranquillizers or psychoactive drugs within 1 week prior to Visit 1,
- •Use of systemic corticosteroids within 3 months prior to Visit 1,
- •Immunization with vaccines within 7 days prior to Visit 2,
- •Patients with hypersensitivity to excipients of the investigational medicinal product,
- •Patients expected to be non-compliant and/or not co-operative,
- •Exposure to any investigational drug within one month or 6 half lives,
- •Patients who have already participated in this study,
- •Patients who are employees of the institution, or 1st grade relatives, or partners of the investigator,
- •Any donation of germ cells, blood, organs, or bone marrow during the course of the study,
- •Patients who are not contractually capable,
- •Nursing (lactating) women or a positive pregnancy test at Visit
- •Persons who are jurisdictional or governmentally institutionalized.
结局指标
主要结局
Conjunctival Provocation Test
时间窗: At screening and after approx 22 weeks (EoS)
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.
次要结局
- Laboratory parameters (immunology)(At screening and after approx. 22 weeks (EoS))
- Conjunctival Provocation Test(after approx. 22 weeks)
- Laboratory (hematological, clinical chemistry, immunological) as a measure of safety(At screening and after approx. 22 weeks (EoS))
- Overall assessment of safety (tolerability)at the end of the study(after approx. 22 weeks (EoS))
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(at 4-weekly intervals (retrospectively at study visits))
- Vital signs: Blood pressure and Heart rate as a measure of safety(At screening and every study visit (4-weekly))
- Patient diary: Allergy specific symptoms and concomitant medication (rescue m.) for 48 hrs after application of study medication(48 hrs every 4 weeks after each application of study medication)
- Physical examination acc to local procedures as a measure of safety(At screening and after approx. 22 weeks (EoS))