A Phase 2b Randomized Blinded Study to Evaluate SYN023 Compared to Human Rabies Immune Globulin in Post Exposure Prophylaxis of Rabies in Adults With Different Rabies Exposure Risks
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 448
- 试验地点
- 14
- 主要终点
- Rabies Virus Neutralizing Activity (RVNA) of Geometric Mean Concentration (GMC) at Study Day 8
研究概览
简要总结
This is a Phase 2b, double blinded, randomized study of SYN023 compared to HyperRab® (a licensed Rabies immune globulin from human sources, HRIG) for the prevention of rabies as part of post-exposure prophylaxis (PEP). The trial will enroll sequentially two different risk substrata of WHO Category 3 rabies exposure which are Low Risk Group (LRG) and Normal Risk Group (NRG). The enrollment will be stepwise while subject's data will be reviewed by data and safety monitoring board (DSMB) to confirm the safety and permit for next enrollment. Besides, rabies vaccine would be administered within 75 minutes after Study Drug in each group.
This trial is proposed to further the licensure of SYN023 to provide an effective PEP alternative available to those exposed persons who need such a product. A placebo-controlled rabies trial is unethical thus HRIG is selected as the control group. Rabies immune globulin from equine and human sources (HRIG) have been evaluated in many trials and HRIG is the standard of care in the United States.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(Low Risk Group):
- •Subjects must meet all of the following criteria at the time of subject ID assignment:
- •History of dog, cat, mongoose, fox, ferret, skunk, bat or raccoon bite to trunk, leg, ankle or foot, or lick or scratch with, or of broken skin or mucous membrane saliva or neural tissue contamination, unprotected physical bat contact, scratch or saliva contamination of the head or neck without broken skin all ≤ 54 hours
- •Has completed the written informed consent process and signed informed consent document
- •Males and females
- •Is age equal or more than 18 years on Study Day 1
- •Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
- •Lives within 2 hour journey by available transportation to study center
- •For female subjects: agrees to avoid pregnancy from Study Day 1 through Study Day
- •Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm with spermicide
- •Inclusion Criteria (Normal Risk Group)
- •Subjects must meet all of the following criteria at the time of subject ID assignment:
- •History of dog, cat, mongoose, fox, ferret, skunk, bat or raccoon bite to any body part, lick or scratch with, or of broken skin, mucous membrane saliva or neural tissue contamination, or unprotected physical bat contact all ≤ 54 hours from post exposure prophylaxis (PEP)
- •Has completed the written informed consent process and signed informed consent document.
- •Males and females
- •Is age equal or more than 18 years on Study Day 1
- •Agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
- •Lives within 2 hour journey by available transportation to study center
- •For female subjects: agrees to avoid pregnancy from agrees to avoid pregnancy from Study Day 1 through Study Day
- •Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm with spermicide
排除标准
- •Subjects must have had none of the following at the time of subject ID assignment:
- •Clinical evidence of rabies infection
- •Category 3 exposure > 54 hours before Study Drug receipt
- •History or serological evidence of previous rabies vaccination
- •Previous receipt of equine or human rabies globulin
- •History of hypersensitivity reaction to equine or human immunoglobulin.
- •Received immunoglobulin or blood products within 42 days before Study Day 1
- •Received any investigational drug therapy or investigational vaccine within 60 days before Study Day 1
- •Planned participation in any other investigational study during the study period.
- •Receiving systemic immunosuppressant medication such as systemic corticosteroids but not limited to systemic corticosteroids
- •History or laboratory evidence of any past, present, or possible immunodeficiency state including but not limited to any laboratory indication of HIV infection
- •Previous medical history that may compromise the safety of the subject in the study according to the opinion of the principal investigator
- •History or evidence on physical examination of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or activity of SYN023
- •Pregnancy (results of the urine pregnancy test MUST be known before enrollment)
研究组 & 干预措施
Normal Risk Group: SYN023+Rabies vaccine
The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). The NRG were consisted of all WHO Category 3 exposure. Subjects were to be allocated with a 1:1 randomization to either SYN023 or Human Rabies Immune Globulin (HRIG) treatment arms.
SYN023:
- Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
- Dosage: 0.3 mg/kg of SYN023
- Frequency/duration: at Day 1
Rabies vaccine:
- Interventions: should be administered in deltoid muscle
- Dosage: 1 mL after reconstitution
- Frequency/duration: at Day 1, 4, 8, 15, 29
干预措施: Rabies vaccine (Biological)
Low Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine
The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). Bites to the head, neck, genitalia arm or hand are not included in the LRG. The initial 20 subjects in the LRG were to be randomized on a 3:1 (SYN023 to Human Rabies Immune Globulin (HRIG)) ratio. The general 60 subjects in the LRG were to be allocated with a 1:1 randomization to either SYN023 or HRIG treatment.
HRIG:
- Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
- Dosage: 20 IU/kg
- Frequency/duration: at Day 1
Rabies vaccine :
- Interventions: should be administered in deltoid muscle
- Dosage: 1 mL after reconstitution
- Frequency/duration: Initial LRG subjects received 4 vaccine doses (Days 1, 4, 8,15); General LRG subjects received 5 vaccine doses (Days 1, 4, 8, 15, and 29)
干预措施: Rabies vaccine (Biological)
Normal Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine
The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). The NRG were consisted of all WHO Category 3 exposure. Subjects were to be allocated with a 1:1 randomization to either SYN023 or Human Rabies Immune Globulin (HRIG) treatment arms.
HRIG:
- Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
- Dosage: 20 IU/kg
- Frequency/duration: at Day 1
Rabies vaccine (RabAvert/Rabipur):
- Interventions: should be administered in deltoid muscle
- Dosage: 1 mL after reconstitution
- Frequency/duration: at Day 1, 4, 8, 15, 29
干预措施: HRIG (HyperRab) (Biological)
Low Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine
The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). Bites to the head, neck, genitalia arm or hand are not included in the LRG. The initial 20 subjects in the LRG were to be randomized on a 3:1 (SYN023 to Human Rabies Immune Globulin (HRIG)) ratio. The general 60 subjects in the LRG were to be allocated with a 1:1 randomization to either SYN023 or HRIG treatment.
HRIG:
- Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
- Dosage: 20 IU/kg
- Frequency/duration: at Day 1
Rabies vaccine :
- Interventions: should be administered in deltoid muscle
- Dosage: 1 mL after reconstitution
- Frequency/duration: Initial LRG subjects received 4 vaccine doses (Days 1, 4, 8,15); General LRG subjects received 5 vaccine doses (Days 1, 4, 8, 15, and 29)
干预措施: HRIG (HyperRab) (Biological)
Low Risk Group: SYN023+Rabies vaccine
The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). Bites to the head, neck, genitalia arm or hand are not included in the LRG. The initial 20 subjects in the LRG were to be randomized on a 3:1 (SYN023 to Human Rabies Immune Globulin (HRIG)) ratio. The general 60 subjects in the LRG were to be allocated with a 1:1 randomization to either SYN023 or HRIG treatment arms.
SYN023:
- Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
- Dosage: 0.3 mg/kg of SYN023
- Frequency/duration: at Day 1
Rabies vaccine:
- Interventions: should be administered in deltoid muscle
- Dosage: 1 mL after reconstitution
- Frequency/duration: Initial LRG subjects received 4 vaccine doses (Days 1, 4, 8,15); General LRG subjects received 5 vaccine doses (Days 1, 4, 8, 15, and 29).
干预措施: Rabies vaccine (Biological)
Low Risk Group: SYN023+Rabies vaccine
The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). Bites to the head, neck, genitalia arm or hand are not included in the LRG. The initial 20 subjects in the LRG were to be randomized on a 3:1 (SYN023 to Human Rabies Immune Globulin (HRIG)) ratio. The general 60 subjects in the LRG were to be allocated with a 1:1 randomization to either SYN023 or HRIG treatment arms.
SYN023:
- Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
- Dosage: 0.3 mg/kg of SYN023
- Frequency/duration: at Day 1
Rabies vaccine:
- Interventions: should be administered in deltoid muscle
- Dosage: 1 mL after reconstitution
- Frequency/duration: Initial LRG subjects received 4 vaccine doses (Days 1, 4, 8,15); General LRG subjects received 5 vaccine doses (Days 1, 4, 8, 15, and 29).
干预措施: SYN023 (Biological)
Normal Risk Group: SYN023+Rabies vaccine
The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). The NRG were consisted of all WHO Category 3 exposure. Subjects were to be allocated with a 1:1 randomization to either SYN023 or Human Rabies Immune Globulin (HRIG) treatment arms.
SYN023:
- Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
- Dosage: 0.3 mg/kg of SYN023
- Frequency/duration: at Day 1
Rabies vaccine:
- Interventions: should be administered in deltoid muscle
- Dosage: 1 mL after reconstitution
- Frequency/duration: at Day 1, 4, 8, 15, 29
干预措施: SYN023 (Biological)
Normal Risk Group: Human Rabies Immune Globulin (HRIG)+Rabies vaccine
The subjects were enrolled in the study sequentially into 2 different risk substrata of WHO Category 3 rabies exposure, which included Low Risk Group (LRG) and Normal Risk Group (NRG). The NRG were consisted of all WHO Category 3 exposure. Subjects were to be allocated with a 1:1 randomization to either SYN023 or Human Rabies Immune Globulin (HRIG) treatment arms.
HRIG:
- Interventions: are administered by direct injection into the wound or by subcutaneous or intramuscular injection when this is not possible
- Dosage: 20 IU/kg
- Frequency/duration: at Day 1
Rabies vaccine (RabAvert/Rabipur):
- Interventions: should be administered in deltoid muscle
- Dosage: 1 mL after reconstitution
- Frequency/duration: at Day 1, 4, 8, 15, 29
干预措施: Rabies vaccine (Biological)
结局指标
主要结局
Rabies Virus Neutralizing Activity (RVNA) of Geometric Mean Concentration (GMC) at Study Day 8
时间窗: Day 8
Rabies Virus Neutralizing Activity (RVNA) was assessed using Rapid Fluorescent Focus Inhibition Test (RFFIT).
Rabies Virus Neutralizing Activity (RVNA) of Geometric Mean Concentration (GMC) at Study Day 99
时间窗: Day 99
Rabies Virus Neutralizing Activity (RVNA) was assessed using Rapid Fluorescent Focus Inhibition Test (RFFIT).
Percentage of Participants With Rabies Virus Neutralizing Activity (RVNA) ≥0.5 IU/mL at Study Day 99
时间窗: Day 99
Rabies Virus Neutralizing Activity (RVNA) was assessed using Rapid Fluorescent Focus Inhibition Test (RFFIT).
Number of Probable or Confirmed Rabies Cases
时间窗: Day 1 to Day 365
Case Classification Human Rabies * Suspected: A case that is compatible with the clinical case definition * Probable: A suspected case (above) plus history of contact with a suspected rabid animal. * Confirmed: A suspected case that is laboratory-confirmed.
次要结局
- Rabies Virus Neutralizing Activity (RVNA) of Geometric Mean Concentration (GMC) at Study Day 4(Day 4)
- Area Under the Efficacy Curve for the Geometric Mean Concentration (GMC) of Rabies Virus Neutralizing Activity (RVNA)(Day 1 to Day 15)
- Maximum Observed Serum Concentration (Cmax)(Day 1 to Day 99)
- Time of Maximum Observed Serum Concentration (Tmax)(Day 1 to Day 99)