COVID-19
Conditions
Keywords
SARS-CoV-2, Coronavirus disease 2019, Severe acute respiratory syndrome coronavirus 2, Immunoglobulins, Immunoglobulins, Intravenous, Antibodies
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALCOVID-HIGIV
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.
OTHERPlacebo (saline)
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.
Sponsors
United States Department of Defense
Emergent BioSolutions
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Able and willing to provide written informed consent (voluntarily signed by the subject) prior to performing study procedures. 2. Females and males 18-60 years of age, inclusive. 3. Have a body mass index (BMI) less than or equal to 35.0 kg/m2. 4. 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). 5. Subject understands and agrees to comply with planned study procedures. 6. 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.
Exclusion criteria
1. 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. 2. 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. 3. History of allergy or hypersensitivity to blood or plasma products or to COVID-HIGIV excipients (proline, PS80). 4. History of allergy to latex or rubber. 5. History of hemolytic anemia. 6. History of Immunoglobulin A (IgA) deficiency. 7. Receipt of any blood product within the past 12 months. 8. Plasma donation within 7 days or significant blood loss or blood donation within 56 days of randomization/dosing. 9. 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). 10. History of thrombosis or hypercoagulable state with increased risk of thrombosis. 11. 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. 12. Receipt of a live vaccine within 28 days prior to screening or anticipated receipt of a live vaccine during the study period. 13. Currently pregnant, breastfeeding, or planning to become pregnant during the study. 14. History of, or suspected substance abuse problem (including alcohol). 15. Other medical condition which may place subject at increased risk due to participation in the study as determined by the investigator. 16. Any planned elective surgery during the study period. 17. An opinion of the investigator that it would be unwise to allow the individual to be randomized into the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics Parameter of Volume of Distribution (Vz) After Dose of COVID-HIGIV | 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 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 | 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 | 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 | 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. |
| Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV | 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 Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIGIV | 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. |
| Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIGIV | 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. |
| Subjects With Adverse Events (AEs) up to 3 Days Post-dosing | Day 1 through Day 4 | Number of subjects with AEs and severity of AEs up to 3 days post-dosing. |
| Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion | 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. |
| Subjects With AEs and SAEs After IV Infusion | Day 1 through Day 85 | Number of subjects with TEAEs and SAEs up to 84 days post-dosing. |
| Total Number of AEs and SAEs After IV Infusion | 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 (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 | 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 (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV | 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 Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIGIV | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) Eligible subjects will be randomized to receive a single IV infusion of COVID-HIGIV dose level 1 (100 mg/kg).
COVID-HIGIV: 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. | 8 |
| COVID-HIGIV Dose Level 2 (200 mg/kg) Eligible subjects will be randomized to receive a single IV infusion of COVID-HIGIV dose level 2 (200 mg/kg).
COVID-HIGIV: 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. | 8 |
| COVID-HIGIV Dose Level 3 (400 mg/kg) Eligible subjects will be randomized to receive a single IV infusion of COVID-HIGIV dose level 3 (400 mg/kg).
COVID-HIGIV: 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. | 7 |
| Dose Placebo (Saline) Eligible subjects will be randomized to receive a single IV infusion of saline placebo.
Placebo (saline): 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. | 4 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 1 |
| Overall Study | Not Treated | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | COVID-HIGIV Dose Level 1 (100 mg/kg) | COVID-HIGIV Dose Level 2 (200 mg/kg) | COVID-HIGIV Dose Level 3 (400 mg/kg) | Dose Placebo (Saline) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 28.4 years STANDARD_DEVIATION 10.2 | 31.5 years STANDARD_DEVIATION 9.5 | 33.9 years STANDARD_DEVIATION 14 | 27.8 years STANDARD_DEVIATION 8.3 | 30.6 years STANDARD_DEVIATION 10.5 |
| Baseline body mass index | 24.1 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 3.7 | 26.9 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 4.5 | 25.9 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 3.2 | 23.5 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 1.2 | 25.3 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 3.7 |
| Baseline weight | 72.2 kilograms STANDARD_DEVIATION 11.9 | 79.3 kilograms STANDARD_DEVIATION 12.4 | 74.1 kilograms STANDARD_DEVIATION 15.9 | 80.8 kilograms STANDARD_DEVIATION 15.7 | 76.1 kilograms STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 6 Participants | 4 Participants | 2 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 173.0 centimeters STANDARD_DEVIATION 8.9 | 172.1 centimeters STANDARD_DEVIATION 12.2 | 168.4 centimeters STANDARD_DEVIATION 12.3 | 184.8 centimeters STANDARD_DEVIATION 14.9 | 173.3 centimeters STANDARD_DEVIATION 12.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 3 Participants | 1 Participants | 14 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 4 Participants | 3 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 7 | 0 / 4 |
| other Total, other adverse events | 3 / 8 | 6 / 8 | 6 / 7 | 3 / 4 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 7 | 1 / 4 |
Outcome results
Primary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIGIV | 583.13 hours | Standard Deviation 237.39 |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIGIV | 752.87 hours | Standard Deviation 257.67 |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIGIV | 618.79 hours | Standard Deviation 148.64 |
Primary
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.
Time frame: Day 1 through Day 85
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV | 3818.25 h*AU/mL |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV | 8255.74 h*AU/mL |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV | 13028.08 h*AU/mL |
Primary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIGIV | 3398.55 h*AU/mL |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIGIV | 6834.66 h*AU/mL |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIGIV | 11722.82 h*AU/mL |
Primary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIGIV | 2961.93 h*AU/mL |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIGIV | 6678.80 h*AU/mL |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIGIV | 11296.33 h*AU/mL |
Primary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV | 7.69 AU/mL |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV | 17.02 AU/mL |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV | 33.27 AU/mL |
Primary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIGIV | 0.0194 mL/h |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIGIV | 0.0188 mL/h |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIGIV | 0.0223 mL/h |
Primary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIGIV | 7.09 hours | Standard Deviation 7.84 |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIGIV | 7.93 hours | Standard Deviation 6.81 |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIGIV | 5.36 hours | Standard Deviation 1.46 |
Primary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV | 2.06 AU/mL |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV | 3.33 AU/mL |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV | 5.47 AU/mL |
Primary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Pharmacokinetics Parameter of Volume of Distribution (Vz) After Dose of COVID-HIGIV | 15.19 mL |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Pharmacokinetics Parameter of Volume of Distribution (Vz) After Dose of COVID-HIGIV | 19.72 mL |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Pharmacokinetics Parameter of Volume of Distribution (Vz) After Dose of COVID-HIGIV | 19.40 mL |
Primary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | 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 | 2961.93 h*Alliance Units (AU)/mL |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | 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 | 6678.80 h*Alliance Units (AU)/mL |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | 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 | 11722.82 h*Alliance Units (AU)/mL |
Primary
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
Population: Safety population includes all subjects who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Subjects With Adverse Events (AEs) up to 3 Days Post-dosing | Subjects with an adverse event (AE) | 3 Participants |
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Subjects With Adverse Events (AEs) up to 3 Days Post-dosing | Subjects with a severe adverse event (SAE) | 0 Participants |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Subjects With Adverse Events (AEs) up to 3 Days Post-dosing | Subjects with a severe adverse event (SAE) | 0 Participants |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Subjects With Adverse Events (AEs) up to 3 Days Post-dosing | Subjects with an adverse event (AE) | 4 Participants |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Subjects With Adverse Events (AEs) up to 3 Days Post-dosing | Subjects with an adverse event (AE) | 6 Participants |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Subjects With Adverse Events (AEs) up to 3 Days Post-dosing | Subjects with a severe adverse event (SAE) | 0 Participants |
| Dose Placebo (Saline) | Subjects With Adverse Events (AEs) up to 3 Days Post-dosing | Subjects with an adverse event (AE) | 2 Participants |
| Dose Placebo (Saline) | Subjects With Adverse Events (AEs) up to 3 Days Post-dosing | Subjects with a severe adverse event (SAE) | 0 Participants |
Primary
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
Population: Safety population includes all subjects who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion | Any TEAE leading to infusion interruption | 1 Participants |
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion | Any TEAE leading to infusion discontinuation | 0 Participants |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion | Any TEAE leading to infusion discontinuation | 0 Participants |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion | Any TEAE leading to infusion interruption | 1 Participants |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion | Any TEAE leading to infusion interruption | 1 Participants |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion | Any TEAE leading to infusion discontinuation | 0 Participants |
| Dose Placebo (Saline) | Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion | Any TEAE leading to infusion interruption | 0 Participants |
| Dose Placebo (Saline) | Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion | Any TEAE leading to infusion discontinuation | 0 Participants |
Primary
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
Population: Safety population includes all subjects who received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Subjects With AEs and SAEs After IV Infusion | Number of subjects with any TEAE | 3 Participants |
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Subjects With AEs and SAEs After IV Infusion | Number of subjects with serious adverse events (SAEs) | 0 Participants |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Subjects With AEs and SAEs After IV Infusion | Number of subjects with serious adverse events (SAEs) | 0 Participants |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Subjects With AEs and SAEs After IV Infusion | Number of subjects with any TEAE | 6 Participants |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Subjects With AEs and SAEs After IV Infusion | Number of subjects with serious adverse events (SAEs) | 0 Participants |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Subjects With AEs and SAEs After IV Infusion | Number of subjects with any TEAE | 6 Participants |
| Dose Placebo (Saline) | Subjects With AEs and SAEs After IV Infusion | Number of subjects with serious adverse events (SAEs) | 1 Participants |
| Dose Placebo (Saline) | Subjects With AEs and SAEs After IV Infusion | Number of subjects with any TEAE | 3 Participants |
Primary
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
Population: Safety population includes all subjects who received any amount of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Total Number of AEs and SAEs After IV Infusion | Total number of adverse events (AEs) for all subjects reporting TEAEs | 5 Events |
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Total Number of AEs and SAEs After IV Infusion | Total number of SAEs for all subjects reporting SAEs | 0 Events |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Total Number of AEs and SAEs After IV Infusion | Total number of SAEs for all subjects reporting SAEs | 0 Events |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Total Number of AEs and SAEs After IV Infusion | Total number of adverse events (AEs) for all subjects reporting TEAEs | 18 Events |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Total Number of AEs and SAEs After IV Infusion | Total number of SAEs for all subjects reporting SAEs | 0 Events |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Total Number of AEs and SAEs After IV Infusion | Total number of adverse events (AEs) for all subjects reporting TEAEs | 19 Events |
| Dose Placebo (Saline) | Total Number of AEs and SAEs After IV Infusion | Total number of adverse events (AEs) for all subjects reporting TEAEs | 8 Events |
| Dose Placebo (Saline) | Total Number of AEs and SAEs After IV Infusion | Total number of SAEs for all subjects reporting SAEs | 1 Events |
Secondary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | 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 | 52.07 h*AU/mL/kg |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | 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 | 105.39 h*AU/mL/kg |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | 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 | 179.39 h*AU/mL/kg |
Secondary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | 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 | 45.90 h*AU/mL/kg |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | 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 | 87.73 h*AU/mL/kg |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | 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 | 161.44 h*AU/mL/kg |
Secondary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | 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 | 41.83 h*AU/mL/kg |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | 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 | 85.23 h*AU/mL/kg |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | 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 | 161.17 h*AU/mL/kg |
Secondary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | 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 | 41.83 h*AU/mL/kg |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | 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 | 85.23 h*AU/mL/kg |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | 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 | 161.44 h*AU/mL/kg |
Secondary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Body-weight Normalized Pharmacokinetics Parameter of Maximum Observed Concentration of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV | 0.11 AU/mL/kg |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Body-weight Normalized Pharmacokinetics Parameter of Maximum Observed Concentration of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV | 0.22 AU/mL/kg |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Body-weight Normalized Pharmacokinetics Parameter of Maximum Observed Concentration of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV | 0.45 AU/mL/kg |
Secondary
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
Population: The PK population included all subjects who received COVID-HIGIV and had an adequate set of evaluable PK samples (a suitable predose sample and at least one measurable postdose sample).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| COVID-HIGIV Dose Level 1 (100 mg/kg) | Body-weight Normalized Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV | 0.0291 AU/mL/kg |
| COVID-HIGIV Dose Level 2 (200 mg/kg) | Body-weight Normalized Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV | 0.0425 AU/mL/kg |
| COVID-HIGIV Dose Level 3 (400 mg/kg) | Body-weight Normalized Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV | 0.0780 AU/mL/kg |