Randomised, Double-blind, Placebo-controlled, Phase I Dose- Escalation Study of Two Doses GHB04L1 in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Occurrence of adverse events
研究概览
简要总结
This study evaluates safety, tolerability and immunogenicity of two doses of GHB04L1, a liquid formulation of the replication- deficient influenza A/Vietnam/1203/04(H5N1)-like ∆NS1 virus in healthy adults. Subjects are randomised at a ratio of 2:1 for GHB04L1 (6.8 log10 or 7.5 log10 TCID50/dose/volunteer) or placebo.
详细描述
GHB04L1 is intended to provide a novel treatment approach for influenza virus H5N1 infection. Based on preclinical data from ferrets that demonstrated protection against challenge with wild-type virus following treatment with various dose levels of GHB04L1, vaccination with GHB04L1 might protect humans from influenza A (H5N1) virus infection.
Due to the lack of the NS1 protein, the ΔNS1 virus replicates efficiently in interferon-deficient cells but has lost its ability to grow in normal hosts and organisms. Immunisation with ΔNS1 mutant virus can cause only an abortive replication cycle in the nasal mucosa of vaccinated individuals. This allows development of replication-deficient intranasal vaccines with genetic stability of the attenuated phenotype and without virus shedding.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female healthy volunteers, 18-50 years of age
- •Seronegative for H5N1 (with antibody titres <1:10 detected in HAI assay)
- •Seronegative for H1N1 (with antibody titres ≤1:20 detected in HAI assay)
- •Written informed consent to participate in this study
排除标准
- •Acute febrile illness (>37.0°C)
- •Positive influenza immunoassay at baseline
- •Signs of acute or chronic upper or lower respiratory tract illnesses (sneezing, cough, tonsillitis, otitis, etc.)
- •History of severe atopy
- •Influenza vaccination 2006/2007 and/or later
- •Known increased tendency of nose bleeding
- •Volunteers with clinically relevant abnormal paranasal anatomy
- •Volunteers with clinically relevant abnormal laboratory values Females with positive urine pregnancy test prior to vaccination
- •Simultaneous treatment with immunosuppressive drugs incl. corticosteroids (≥ 2 weeks) within 4 weeks prior to study medication application
- •Clinically relevant history of renal, hepatic, GI, cardiovascular, haematological, skin, endocrine, neurological or immunological diseases
- •History of leukaemia or cancer
- •HIV or hepatitis B or C seropositivity
- •Volunteers who had undergone rhino or sinus surgery or surgery of another traumatic injury of the nose within 30 days prior to application of study medication
- •Volunteers who had received antiviral drugs, treatment with immunoglobulins or blood transfusions or an investigational drug within four weeks prior to study medication application
- •Volunteers who had received anti-inflammatory drugs 2 days prior to study medication application
- •Volunteers who were not likely to cope with the requirements of the study or with a significant physical or mental condition that may interfere with the completion of the study
研究组 & 干预措施
GHB04L1
GHB04L1 is administered as intranasal aerosol at a dose of 6.8 log10 or 7.5 log10 TCID50/dose/subject on day 1 and on day 29.
干预措施: GHB04L1 (Biological)
Placebo
Placebo (buffer) is administered as intranasal aerosol on day 1 and on day 29.
干预措施: Placebo (Other)
结局指标
主要结局
Occurrence of adverse events
时间窗: 8 weeks
Occurrence of local and systemic adverse events overall and within 7 days after each study medication administration
次要结局
- Local cytokines response(3 days)
- Systemic influenza A virus-specific antibody response(8 weeks)
- Viral shedding(3 days)
- Local immune response(8 weeks)
- Systemic natural killer cell cytotoxicity(5 weeks)
- Systemic influenza A virus-specific T-cell response(8 weeks)
- Systemic T-cell Granzyme B assay(8 weeks)