A Phase 1, Double-blind, Randomized, Placebo-controlled Study to Evaluate Safety and Pharmacokinetics of Anti-SARS-CoV-2 Immunoglobulin Intravenous (Human) Investigational Product (COVID-HIGIV) Administered as a Single Dose Regimen to Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Subjects With Adverse Events (AEs) up to 3 Days Post-dosing
研究概览
简要总结
This study is designed to evaluate three dose levels of Anti-SARS-CoV-2 Immunoglobulin Intravenous (Human) (COVID-HIGIV) for safety and pharmacokinetics (PK) in healthy adults. Twenty-eight healthy adult subjects will be enrolled into the study to receive a single dose of COVID-HIGIV or placebo with 84 days of safety and PK follow-up post-administration.
详细描述
This study will be a Phase 1, single-center, randomized, double-blind, placebo-controlled design to assess safety and PK of COVID-HIGIV in healthy adults.
In total, 28 healthy adult subjects are to be enrolled and randomized 2:2:2:1 into four study treatment arms to receive a single intravenous (IV) infusion of one of three COVID-HIGIV dose levels or saline placebo, respectively.
The enrollment/dosing of the first seven subjects in the study will be staggered. Available safety data will be reviewed by Study Monitoring Committee (SMC) after seven subjects have completed at least 72 hours of safety follow-up. Subjects will be followed up for safety and PK up to 84 days post-administration.
The SMC will perform overall ongoing review of safety data during 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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Able and willing to provide written informed consent (voluntarily signed by the subject) prior to performing study procedures.
- •Females and males 18-60 years of age, inclusive.
- •Have a body mass index (BMI) less than or equal to 35.0 kg/m
- •Women who are either:
- •A) Not of childbearing potential: either surgically sterile (at least six weeks post bilateral tubal ligation, bilateral oophorectomy or hysterectomy); or post-menopausal (defined as ≥50 years of age with a history of ≥12 months without menses prior to randomization in the absence of other pathologic or physiologic causes, following cessation of exogenous sex-hormonal treatment); OR
- •B) Women of childbearing potential (WOCBP) who are not planning to be pregnant during the study period and meet all of the following criteria:
- •Negative serum pregnancy test (PT) at Screening; and Negative PT prior to dosing at Day 1; and
- •Use of a highly effective contraception during the study period:
- •Hormonal contraceptives (e.g., implants, pills, patches) initiated ≥30 days prior to Day 1; or
- •Intrauterine device (IUD) inserted ≥30 days prior to Day 1; or
- •Double barrier type of birth control (e.g., male condom with female diaphragm, male condom with cervical cap).
- •Subject understands and agrees to comply with planned study procedures.
- •Healthy as determined by the Principal Investigator based on medical history, physical exam, vital signs, urinalysis, blood chemistry and hematology test results at Screening and evidence of no prior exposure to SARS-CoV-2 (i.e., Reverse transcription polymerase chain reaction [RT-PCR] negative for SARS-CoV-2 and negative for SARS-CoV-2 antibodies) at Screening.
排除标准
- •Use of any investigational product, within 30 days prior to Screening, or use of investigational SARS-CoV-2 vaccines, SARS-CoV-2 monoclonal antibodies or COVID-19 convalescent plasma at any time prior to Screening or during the study follow-up period, or subject plans to participate in another clinical study during the study period.
- •Screening clinical laboratory test result greater than the laboratory's upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), random glucose, total and/or bilirubin, blood urea nitrogen (BUN), or creatinine. Other serum chemistry parameters that are not within the reference range will not be considered exclusionary unless deemed clinically significant by the Principal Investigator.
- •History of allergy or hypersensitivity to blood or plasma products or to COVID-HIGIV excipients (proline, PS80).
- •History of allergy to latex or rubber.
- •History of hemolytic anemia.
- •History of Immunoglobulin A (IgA) deficiency.
- •Receipt of any blood product within the past 12 months.
- •Plasma donation within 7 days or significant blood loss or blood donation within 56 days of randomization/dosing.
- •History of known congenital or acquired immunodeficiency or receipt of immunosuppressive therapy (e.g., prednisone or equivalent for more than two consecutive weeks within the past three months).
- •History of thrombosis or hypercoagulable state with increased risk of thrombosis.
- •History of clinically significant chronic illness (e.g., requiring hospitalization in the past three months) such as cardiac, pulmonary, renal, hepatic or other chronic conditions.
- •Receipt of a live vaccine within 28 days prior to screening or anticipated receipt of a live vaccine during the study period.
- •Currently pregnant, breastfeeding, or planning to become pregnant during the study.
- •History of, or suspected substance abuse problem (including alcohol).
- •Other medical condition which may place subject at increased risk due to participation in the study as determined by the investigator.
- •Any planned elective surgery during the study period.
- •An opinion of the investigator that it would be unwise to allow the individual to be randomized into the study.
研究组 & 干预措施
COVID-HIGIV Dose Level 1 (100 mg/kg)
Eligible subjects randomized to receive a single IV infusion of COVID-HIGIV dose level 1 (100 mg/kg).
干预措施: COVID-HIGIV (Biological)
COVID-HIGIV Dose Level 2 (200 mg/kg)
Eligible subjects randomized to receive a single IV infusion of COVID-HIGIV dose level 2 (200 mg/kg).
干预措施: COVID-HIGIV (Biological)
COVID-HIGIV Dose Level 3 (400 mg/kg)
Eligible subjects randomized to receive a single IV infusion of COVID-HIGIV dose level 3 (400 mg/kg).
干预措施: COVID-HIGIV (Biological)
Dose Placebo (saline)
Eligible subjects randomized to receive a single IV infusion of saline placebo.
干预措施: Placebo (saline) (Other)
结局指标
主要结局
Subjects With Adverse Events (AEs) up to 3 Days Post-dosing
时间窗: Day 1 through Day 4
Number of subjects with AEs and severity of AEs up to 3 days post-dosing.
Subjects With AEs and SAEs After IV Infusion
时间窗: Day 1 through Day 85
Number of subjects with TEAEs and SAEs up to 84 days post-dosing.
Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV
时间窗: Day 1 through Day 85
Area under the concentration-time curve from time 0 to the last quantifiable concentration plus the additional area extrapolated to infinity of SARS-CoV-2 binding IgG antibodies after COVID-HIGIV dose. Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57 and Day 85.
Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIGIV
时间窗: Day 1 through Day 85
The apparent terminal elimination half-life (T1/2) after dose of COVID-HIGIV. Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57 and Day 85.
Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion
时间窗: 0 hours to 2.5 hours
Number of subjects and severity of treatment emergent adverse events (TEAEs) that led to discontinuation or temporary suspension of IV infusion.
Total Number of AEs and SAEs After IV Infusion
时间窗: Day 1 through Day 85
Number of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) in all subjects reporting TEAEs/SAEs up to 84 days post-dosing.
Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIGIV
时间窗: Day 1 through Day 85
The systemic clearance (CL) of SARS-CoV-2 binding IgG antibodies after dose of COVID-HIGIV. Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57 and Day 85.
Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIGIV
时间窗: Day 1 through Day 15
AUC from time 0 to 14 days (AUC0-14d) of SARS-CoV-2 binding IgG antibodies after COVID-HIGIV. Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, and Day 15.
Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV
时间窗: Day 1 through Day 29
The observed trough concentration of SARS-CoV-2 binding IgG antibodies 28 days after COVID-HIGIV dose. Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, Day 15, Day 22, and Day 29.
Pharmacokinetics Parameter of Volume of Distribution (Vz) After Dose of COVID-HIGIV
时间窗: Day 1 through Day 85
The volume of distribution (Vz) of SARS-CoV-2 binding IgG antibodies after dose of COVID-HIGIV. Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57 and Day 85.
Pharmacokinetics (PK) Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-last) of SARS-CoV-2 Antibodies After Dose of COVID-HIGIV
时间窗: Day 1 through Day 85
The area under the concentration-time curve from time 0 to the last quantifiable concentration of SARS-CoV-2 binding IgG antibodies after COVID-HIGIV dose. Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57 and Day 85.
Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIGIV
时间窗: Day 1 through Day 29
AUC from time 0 to 28 days of SARS-CoV-2 binding IgG antibodies after COVID-HIGIV dose. Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, Day 15, Day 22, and Day 29.
Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV
时间窗: Day 1 through Day 85
The Cmax of SARS-CoV-2 binding IgG antibodies observed after COVID-HIGIV dose. Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57 and Day 85.
Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIGIV
时间窗: Day 1 through Day 85
Time at which Cmax occurs (Tmax) after COVID-HIGIV at each dose level .Data for PK calculations was collected: pre-dose within 2 hrs prior to dosing, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57 and Day 85.
次要结局
- Body-weight Normalized Pharmacokinetics Parameter of Maximum Observed Concentration of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV(Day 1 through Day 85)
- Body-weight Normalized Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Quantifiable Concentration (AUC0-last) of SARS-CoV-2 Antibodies After Dose of COVID-HIGIV(Day 1 through Day 85)
- Body-weight Normalized Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to the Last Quantifiable Concentration of SARS-CoV-2 Antibodies Plus the Additional Area Extrapolated to Infinity (AUC0-inf) After Dose of COVID-HIGIV(Day 1 through Day 85)
- Body-weight Normalized Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days (AUC0-14d) After Dose of COVID-HIGIV(Day 1 through Day 15)
- Body-weight Normalized Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIGIV(Day 1 through Day 29)
- Body-weight Normalized Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV(Day 1 through Day 29)