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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
28
COVID-HIGIV is a purified immunoglobulin G (IgG) liquid preparation containing antibodies (including neutralizing antibodies) to SARS-CoV-2. COVID-HIGIV will be administered via intravenous infusion.
The reference product is a liquid solution of normal saline (0.9% weight per unit volume (w/v) sodium chloride). Placebo will be administered via intravenous infusion.
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Subjects With Adverse Events (AEs) up to 3 Days Post-dosing
Number of subjects with AEs and severity of AEs up to 3 days post-dosing.
Time frame: Day 1 through Day 4
Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion
Number of subjects and severity of treatment emergent adverse events (TEAEs) that led to discontinuation or temporary suspension of IV infusion.
Time frame: 0 hours to 2.5 hours
Subjects With AEs and SAEs After IV Infusion
Number of subjects with TEAEs and SAEs up to 84 days post-dosing.
Time frame: Day 1 through Day 85
Total Number of AEs and SAEs After IV Infusion
Number of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) in all subjects reporting TEAEs/SAEs up to 84 days post-dosing.
Time frame: Day 1 through 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
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.
Time frame: Day 1 through Day 85
Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV
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.
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Time frame: Day 1 through Day 85
Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIGIV
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.
Time frame: Day 1 through Day 15
Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIGIV
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.
Time frame: Day 1 through Day 29
Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV
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.
Time frame: Day 1 through Day 85
Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIGIV
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.
Time frame: Day 1 through Day 85
Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV
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.
Time frame: Day 1 through Day 29
Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIGIV
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.
Time frame: Day 1 through Day 85
Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIGIV
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.
Time frame: Day 1 through Day 85
Pharmacokinetics Parameter of Volume of Distribution (Vz) After Dose of COVID-HIGIV
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.
Time frame: Day 1 through Day 85
Body-weight Normalized Pharmacokinetics Parameter of Maximum Observed Concentration of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV
The body-weight normalized Cmax (CmaxBWN) of SARS-CoV-2 binding 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.
Time frame: 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
The body-weight normalized 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.
Time frame: 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
The body-weight normalized 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.
Time frame: 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
Body-weight normalized AUC from time 0 to 14 days 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.
Time frame: 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
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.
Time frame: 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
The body-weight normalized 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.
Time frame: Day 1 through Day 29