A Randomized, Double-blind, Placebo Controlled Study to Assess the Safety and Tolerability of HAL-MRE1 Subcutaneous Immunotherapy in Adult Subjects With Ragweed Induced Allergic Rhinitis/Rhinoconjunctivitis With or Without Asthma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Occurence of local and systemic reactions
研究概览
简要总结
The aim of this first-in-human phase I study is to assess the safety and tolerability of HAL-MRE1 subcutaneous immunotherapy in subjects suffering from ragweed pollen-induced allergic rhinitis/rhinoconjunctivitis with or without asthma.
The study has 4 treatment groups: 1 placebo group and 3 groups treated with different doses of HAL-MRE1.
详细描述
A chemically modified, aluminum hydroxide adsorbed ragweed extract (HAL-MRE1) for subcutaneous administration was developed for the treatment of ragweed pollen-induced allergic rhinitis/rhinoconjunctivitis (ARC) with or without asthma. The aim of this first-in-human phase I study is to assess the safety and tolerability of HAL-MRE1 subcutaneous immunotherapy in subjects suffering from ragweed pollen-induced ARC with or without asthma.
The study will consist of 3 staggered cohorts of 15 subjects each who are randomly assigned to the active or placebo group in a 2:1 manner using block randomization.
A one month gap must be maintained between the end of the ragweed pollen peak season (2018) and subject randomization into the study. The study has seasonal constraints; subjects with concomitant tree and/or grass pollen allergies must complete study treatment before any allergy symptoms due to tree and/or grass pollen exposure develop or start study treatment after the symptoms caused by the tree and/or grass pollen exposure have disappeared.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent.
- •Male or female subjects aged ≥18 and ≤65 years.
- •Documented diagnosis of allergic rhinitis/rhinoconjunctivitis (ARC) to ragweed pollen. A documented diagnosis is a documented medical history of ARC symptoms that required treatment after ragweed pollen exposure. Subjects experienced allergy symptoms that required treatment during the previous 2 ragweed seasons, with or without concomitant asthma (asthma must be controlled).
- •Positive nasal provocation test for ragweed pollen at screening or within the last 6 months.
- •Positive skin prick test to ragweed allergen at screening or within the last 6 months.
- •Positive serum specific IgE test for ragweed allergen (IgE level ≥0.7 U/mL).
- •Forced expiratory volume >70 % or peak expiratory flow >80 % of predicted value.
- •For asthmatic subjects: asthma control test (ACT) score ≥
- •Subjects are capable and willing to maintain a log of adverse events and concomitant medication throughout the study, as well as to complete a diary 24 hours post investigational medical product injection.
- •Negative pregnancy test at screening for females of childbearing potential.
- •Females of childbearing age must be using an effective method of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the study. Contraceptive measures considered adequate are:
- •hormonal contraceptives such as contraceptive pills, transdermal patches, intrauterine devices, intrauterine system implants, or vaginal rings (started at least 4 weeks prior to investigational medical product administration).
- •double barrier methods e.g. condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent.
- •sterilization (male or female).
- •participants who are postmenopausal (12 consecutive months without a period) for at least 2 years.
- •sexual abstinence or having no sexual relationship with a man.
排除标准
- •History of anaphylaxis with cardio respiratory symptoms (food allergy, venom allergy, drugs or/and idiopathic reaction).
- •Alcohol, drug or medication abuse in the past.
- •Any clinically significant abnormal laboratory parameter at screening as per investigator's discretion.
- •Clinically relevant sensitization to other allergens if clinical symptoms are expected during the study.
- •Uncontrolled asthma.
- •Participation in a clinical interventional study within the last 3 months (e.g. new investigational drug or biological), or plans to participate in another clinical trial during this study, or participation in an observational study (e.g. post marketing study) within the last 30 days unless the observational study aimed to investigate the intradermal test.
- •Subjects who received immunotherapy for any specific allergen 3 years prior to screening or during the study period.
- •Subjects who were ever treated with any ragweed allergen specific immunotherapy.
- •Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs.
- •Subjects undergoing any immunosuppressive treatment (including anti-IgE therapy) within the last 6 months prior to inclusion in the study as well as during the study.
- •Active malignancies or any malignant disease during the 5 years prior to screening.
- •Severe uncontrolled diseases that, in the opinion of the investigator, could increase the risk for subjects participating in the study, including but not limited to: any severe or unstable lung diseases; endocrine diseases; clinically significant renal or hepatic diseases, or hematological disorders; or severe ongoing symptomatic allergic diseases.
- •Active or acute inflammation or infection of the target organs (nose, eyes) at screening.
- •Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma).
- •Severe psychiatric, psychological, or neurological disorders.
- •Subjects who have any direct working relationship with the (sub-) investigator or study site personnel or are first degree relatives or partners of the investigator or study site personnel or are employees of the sponsor.
- •Known allergy or hypersensitivity to an excipient in the study drug or placebo.
- •Subjects receiving the prohibited previous and concomitant medication.
研究组 & 干预措施
HAL-MRE1 5,000 AUeq
10 subjects will receive HAL-MRE1 5,000 AUeq. Subjects will receive 6-8 incremental weekly injections until reaching the maximum dose of 5,000 AUeq. Subsequently, 1 repeated maximum dose injection will be given 1 week later (total treatment period will be approximately 7-9 weeks). All doses will be subcutaneously injected in a double-blind fashion in the upper arm.
干预措施: HAL-MRE1 (Biological)
HAL-MRE1 10,000 AUeq
10 patients will receive HAL-MRE1 10,000 AUeq. Subjects will receive 6-8 incremental weekly injections until reaching the maximum dose of 10,000 AUeq. Subsequently, 1 repeated maximum dose injection will be given 1 week later (total treatment period will be approximately 7-9 weeks). All doses will be subcutaneously injected in a double-blind fashion in the upper arm.
干预措施: HAL-MRE1 (Biological)
HAL-MRE1 0 AUeq
15 subjects will receive placebo. Subjects will receive 7-9 incremental weekly injections. All doses will be subcutaneously injected in a double-blind fashion in the upper arm.
干预措施: HAL-MRE1 (Biological)
HAL-MRE1 20,000 AUeq
10 patients will receive HAL-MRE1 20,000 AUeq. Subjects will receive 6-8 incremental weekly injections until reaching the maximum dose of 20,000 AUeq. Subsequently, 1 repeated maximum dose injection will be given 1 week later (total treatment period will be approximately 7-9 year). All doses will be subcutaneously injected in a double-blind fashion in the upper arm.
干预措施: HAL-MRE1 (Biological)
结局指标
主要结局
Occurence of local and systemic reactions
时间窗: Through study completion, approximately 10 weeks
Number, intensity and seriousness of early (within 30 mins from injection), delayed (within 30mins and 3 hours from injection) and late (from 3 hours to 24 hours after injection) local reactions (\>8 cm wheal size swelling at injection site) as well as early, delayed and late systemic reactions.
次要结局
- Occurence of other local reactions(Through study completion, approximately 10 weeks)
- Number of subjects that reach maximum dose(Through study completion, approximately of 10 weeks)
- Number of injections to reach maintenance dose(Through study completion, approximately of 10 weeks)
- Change in wheal size after skin prick test(Pre-treatment and after the repeated maintenance dose visit (after 8 to 10 weeks))
- Occurrence of treatment emergent adverse events(Through study completion, approximately of 10 weeks)
- Immunoglobulin Levels(Pre-treatment and after the repeated maintenance dose visit (after 8 to 10 weeks))