A Phase 2 Randomized Blinded Placebo Controlled Comparison of the Safety Pharmacokinetics and Pharmacodynamics of a Single Dose of SYN023 Administered With Licensed Rabies Vaccines in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 164
- 试验地点
- 2
- 主要终点
- Percentage of Participants With Serum Rabies Virus Neutralizing Activity
研究概览
简要总结
This is single site, randomized, blinded comparison of the immunogenicity, of Imovax (RVi) and Rabavert (RVa) rabies vaccines when subjects are administered rabies immune globulin (RIG) or SYN023. Subjects will be randomized into one of four dose groups: RVi + SYN023, RVi+RIG, RVa+SYN023 and RVa+RIG. The initial dose of RVi and RVa will be co-administered with either RIG or SYN023). Rabies virus neutralizing activity (RVNA) and blood levels of SYN023 will be measured for the remainder of the trial while the rest of the five RVi and RVa doses are given. The study will last 112 days. SYN023 concentrations and anti-SYN023 antibodies will also be measured.
详细描述
Administered immunoglobulins directed against vaccine antigens have the potential to inhibit the immune response to a vaccine. Both vaccination and immune globulin are used together in the post exposure prophylaxis of rabies virus infection. SYN023 (a mixture of two monoclonal antibodies CTB011 and CTB012) may be used instead of human rabies immune globulin. Since there is a risk of antagonism of vaccine induced immunity by SYN023, as there is with rabies immune globulin, it is necessary to study possible interactions of these two agents that might be used concurrently. This is single site, randomized, blinded comparison of the immunogenicity, of Imovax (RVi) and Rabavert (RVa) rabies vaccines when administered concurrently with rabies immune globulin (RIG) or SYN023. Subjects will be randomized into one of four dose groups: RVi + SYN023, RVi + RIG, RVa+SYN023 and RVa + RIG. The initial dose of RVi and RVa will be co-administered with either RIG or SYN023). The remaining 4 doses of RVi and RVa will be administered intramuscularly as specified in the product labeling. Serum rabies virus neutralizing activity (RVNA) and serum concentrations of the components of of SYN023 will be measured for the remainder of the trial while the rest of the five RVi and RVa doses are given. Adverse events will be collected for the duration of the trial. The study will last 112 days. Anti-SYN023 antibodies will also be measured.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
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 subjects between 18 and 50 years of age, inclusive
- •Body mass index between 18 and 30 kg/m², inclusive
- •Female subjects physically capable of pregnancy (i.e., not sterilized and still menstruating or within 1 year of the last menses if menopausal) must:
- •Agree to avoid pregnancy from 28 days prior to Study Day 0 through the duration of the study.
- •If in a sexual relationship with a man, use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include: the use of at least two forms of contraception, including use by a partner of a barrier method (e.g., male condom with intravaginal spermicide) as one form of contraception.
- •Women of childbearing potential must have a negative serum pregnancy test within 24 hours preceding receipt of each dose.
- •Can understand and sign the informed consent document, can communicate with the investigator and provide updated contact information as needed for the duration of the study, has no current plans to move from the study area for the duration of the study, and can understand and comply with the requirements of the protocol.
排除标准
- •Oral temperature ≥37.5°C at screening
- •Complete blood count (CBC) and platelet count abnormal values (>5% above the upper limit of normal [ULN] or >5% below the lower limit of normal [LLN] per local laboratory parameters) at screening with exception of absolute lymphocyte count.
- •Abnormally elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase (ALP), or creatinine (Cr) values at screening (however a single test AST, ALT or ALP may be >10% above the ULN per local laboratory parameters)
- •Abnormal PT (INR) PTT
- •Abnormal screening urinalysis result that is, per the investigator, clinically significant, or a screening urine dipstick result of ≥2+ protein
- •Positive screening urine test for illicit drugs (opiates, cocaine, amphetamines methamphetamines, barbiturates, benzodiazepines, tetrahydrocannabinol, PCP, MDMA, and methadone)
- •History or evidence of autoimmune disease
- •History or evidence of any past, present, or future possible immunodeficiency state, including laboratory evidence of human immunodeficiency virus (HIV) 1 or 2 infection
- •History or evidence of chronic hepatitis
- •History or evidence of rabies infection
- •History or evidence of any other acute or chronic disease that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the drug or compromise the safety of the subject; for example a clinically relevant history of respiratory, thyroid, gastrointestinal, renal, hepatic, hematological, lymphatic, oncologic, cardiovascular, psychiatric, neurological, musculoskeletal, genitourinary, infective, inflammatory, immunological, dermatological or connective tissue disease
- •History or evidence of allergic disease or reaction, including adverse responses to therapeutic monoclonal antibodies that, in the opinion of the investigator, may compromise the safety of the subject
- •History of non-compliance that, in the opinion of the investigator, will make it unlikely that the subject will comply with the protocol
- •Previous exposure to rabies vaccine
- •Receipt of an immunoglobulin or blood product within 90 days prior to Study Day 0
- •Receipt of immunosuppressive medications other than inhaled or topical immunosuppressant drugs within 45 days prior to Study Day 0
- •Body weight greater than 90 kg.
- •History or evidence of IgA deficiency
研究组 & 干预措施
Imovax, SYN023
Subjects will receive SYN023 and 5 doses of Imovax rabies vaccine
干预措施: Imovax (Biological)
Imovax, human rabies immune globulin
Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
干预措施: Imovax (Biological)
Imovax, human rabies immune globulin
Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of Imovax rabies vaccine
干预措施: HyperRAB ST (human rabies immune globulin) (Biological)
RabAvert, SYN023
Subjects will receive SYN023 and 5 doses of RabAvert rabies vaccine
干预措施: RabAvert (Biological)
RabAvert, human rabies immune globulin
Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine
干预措施: RabAvert (Biological)
RabAvert, human rabies immune globulin
Subjects will receive HyperRAB ST (human rabies immune globulin) and 5 doses of RabAvert rabies vaccine
干预措施: HyperRAB ST (human rabies immune globulin) (Biological)
RabAvert, SYN023
Subjects will receive SYN023 and 5 doses of RabAvert rabies vaccine
干预措施: SYN023 (Biological)
Imovax, SYN023
Subjects will receive SYN023 and 5 doses of Imovax rabies vaccine
干预措施: SYN023 (Biological)
结局指标
主要结局
Percentage of Participants With Serum Rabies Virus Neutralizing Activity
时间窗: 112 days
Inhibitory activity of serum in standard rabies virus inhibition test (RFFIT: Rapid Fluorescent Foci Inhibition Test) assessed as serum RVNA ≥ 0.5 IU/mL. RFFIT is a serum neutralization (inhibition) test, which means it measures the ability of rabies specific antibodies to neutralize rabies virus and prevent the virus from infecting cells. These antibodies are called rabies virus neutralizing antibodies (RVNA).
次要结局
- Percentage of Participants With Adverse Event Incidence of SYN023 Compared to HRIG in RabAvert and Imovax Reciptients(42 days)
- Percentage of Participants With Immunogenicity: Anti-CTB012 Antibodies Positive(112 days)
- Percentage of Participants With Immunogenicity: Anti-CTB011 Antibodies Positive(112 days)
- SYN023 Monoclonal Antibody Areas Under the Curve (AUC0-last, AUC0-inf) for CTB011 and CTB012)(84 days)
- Time to Maximum Concentration Tmax of CTB011 and CTB012(84 days)
- Maximum Serum Concentration Cmax(84 days)
- Serum Clearance Rate (Clp) of CTB011 and CTB012(84 days)
- Serum Half Lives of CTB011 and CTB012(84 days)