The primary objectives of this open-label trial were to evaluate the safety and pharmacokinetics (PK) of Anti-SARS-CoV-2 Immunoglobulin (Human) Investigational Product (COVID-HIG) administered intramuscularly (IM), subcutaneously (SC), or intravenously (IV) as a single dose in healthy adults 18-59 years of age with body mass index ≤35 kg/m\^2. Prior studies examined IV administration, and the secondary objective of the present study was to compare PK among the three administration routes. No placebo group was included in the phase 1 randomized design. The exploratory objective was to evaluate disease severity in participants that became positive for SARS-CoV-2.
Eligible participants were randomized in two cohorts to receive COVID-HIG by IM, SC or IV in a 1:1:1 ratio and were stratified based on baseline SARS-CoV-2 IgG antibody status (low seropositive/seronegative; high seropositives were excluded). Up to 36 participants were planned to be enrolled and dosed in the study. A protocol amendment truncated the study to 23 randomized participants due to the impact of high circulating SARS-CoV-2 omicron cases on enrollment and participant retention. Participants were planned to be followed through Day 85 (approximately three half-lives), but the protocol was amended to shorten the study length to Day 57 due to timeline and PK considerations. The third substantial protocol amendment change was to remove the planned pseudovirus neutralization assay from the study due to its low sensitivity, limiting the PK analysis to the S-protein binding IgG immunoassay. PK time points included predose and postdose (from end of infusion/injection) 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, Days 2, 3, 4, 6, 8, 15, 29, 43 and 57. Nasopharyngeal swabs for SARS-CoV-2 were collected throughout the study. Per protocol, participants who became SARS-CoV-2 positive could not be assessed for PK at time points after testing positive, as the assay could not distinguish COVID-HIG from native antibodies. Participants who became SARS-CoV-2 positive during the study had disease severity assessed using an Ordinal Outcome Scale and followed via telemedicine through the end of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Anti-SARS-CoV-2 Immunoglobulin (Human) \[COVID-HIG\] is a purified liquid immunoglobulin G (IgG) preparation
Qps-Mra, Llc
Miami, Florida, United States
Bio-Kinetic Clinical Applications, LLC
Springfield, Missouri, United States
Participants With Adverse Events (AEs) up to 72 Hours Post-dosing
Number of participants with AEs and severity of AEs up to 72 hours post-dosing.
Time frame: 72 hours
Participants With Adverse Events That Led to Discontinuation or Temporary Suspension of Study Treatment
Number of participants and severity of AEs that led to discontinuation or temporary suspension of study treatment.
Time frame: Day 1
Participants With AEs and SAEs After Study Treatment
Number of participants with adverse events (AEs) and serious adverse events (SAEs) up to 56 days post-administration of a single dose of COVID-HIG.
Time frame: Day 0 to Day 57
Total Number of AEs and SAEs After Study Treatment
Number of adverse events (AEs) and serious adverse events (SAEs) in all participants reporting AEs/SAEs up to 56 days post-dosing.
Time frame: Day 0 to Day 57
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-HIG
The area under the concentration-time curve from time 0 to the last quantifiable concentration of SARS-CoV-2 binding IgG antibodies after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
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-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIG
The Cmax of SARS-CoV-2 binding IgG antibodies observed after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIG
Time at which Cmax occurs (Tmax) after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIG
The observed trough concentration of SARS-CoV-2 binding IgG antibodies 28 days after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, and Day 29.
Time frame: Day 1 to Day 29
Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIG.
AUC from time 0 to 28 days of SARS-CoV-2 binding IgG antibodies after COVID-HIG dose. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, and Day 29.
Time frame: Day 1 to Day 29
Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIG
AUC from time 0 to 14 days (AUC0-14d) of SARS-CoV-2 binding IgG antibodies after COVID-HIG. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, and Day 15.
Time frame: Day 1 to Day 15
Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIG
The apparent terminal elimination half-life (T1/2) after dose of COVID-HIG. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIG
The systemic clearance (CL) of SARS-CoV-2 binding IgG antibodies after dose of COVID-HIG. . Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
Pharmacokinetic Parameter of Volume of Distribution (Vz) After Dose of COVID-HIG
The volume of distribution (Vz) of SARS-CoV-2 binding IgG antibodies after dose of COVID-HIG. Data for PK calculations was collected: pre-dose, and post-dose at: 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, Day 3, Day 4, Day 6, Day 8, Day 15, Day 29, Day 43, and Day 57.
Time frame: Day 1 to Day 57
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