A COVID-19 Study to Evaluate Safety and Pharmacokinetics of COVID-HIGIV Administered in Healthy Adults

Sponsor

Emergent BioSolutions (Industry)

Overall Status

Completed

CT.gov ID

NCT04661839

Collaborator

United States Department of Defense (U.S. Fed)

Enrollment

Location

Arms

7.1

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Biological: COVID-HIGIV Other: Placebo (saline)	Phase 1

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 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 Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 24, 2020

Actual Primary Completion Date :

Jul 27, 2021

Actual Study Completion Date :

Jul 27, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: COVID-HIGIV Dose Level 1 Eligible subjects will be randomized to receive a single IV infusion of COVID-HIGIV dose level 1.	Biological: 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. Other Names: NP-028
Experimental: COVID-HIGIV Dose Level 2 Eligible subjects will be randomized to receive a single IV infusion of COVID-HIGIV dose level 2.	Biological: 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. Other Names: NP-028
Experimental: COVID-HIGIV Dose Level 3 Eligible subjects will be randomized to receive a single IV infusion of COVID-HIGIV dose level 3.	Biological: 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. Other Names: NP-028
Placebo Comparator: Dose Placebo (saline) Eligible subjects will be randomized to receive a single IV infusion of saline placebo.	Other: 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.

Outcome Measures

Primary Outcome Measures

Number of Subjects with Adverse Events (AEs) post-dosing [Day 1 through Day 3]
Incidence and severity of AEs up to 3 days post-dosing.
Number of Subjects with Adverse Events that Led to Discontinuation or Temporary Suspension of IV Infusion [0 hours to 2.5 hours]
Incidence and severity of AEs that led to discontinuation or temporary suspension of IV infusion.
Number of Subjects with AEs after IV Infusion [Day 1 through Day 85]
Incidence and severity of AEs up to 84 days
Number of Subjects with SAEs after IV Infusion [Day 1 through Day 85]
Incidence and severity of SAEs up to 84 days.
Pharmacokinetics parameter of area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-t) 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 after COVID-HIGIV dose.
Pharmacokinetics parameter of area under the concentration-time (AUC) from time 0 to the last quantifiable concentration (AUC0-t) of SARS-CoV-2 antibodies plus the additional area extrapolated to infinity (AUC0-inf) after dose of COVID-HIGIV [Day 1 through Day 85]
AUC0-t plus the additional area extrapolated to infinity after COVID-HIGIV dose.
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]
AUC from time 0 to 14 days after COVID-HIGIV.
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 after COVID-HIGIV dose.
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 observed after COVID-HIGIV dose.
Pharmacokinetics parameter of time at which Cmax occurs after dose of COVID-HIGIV [Day 1 through Day 85]
Time at which Cmax occurs after COVID-HIGIV at each dose level.
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 28 days after COVID-HIGIV dose.
Pharmacokinetics parameter of terminal elimination constant after dose of COVID-HIGIV [Day 1 through Day 85]
The terminal elimination rate constant after COVID-HIGIV dose.
Pharmacokinetics parameter of apparent terminal elimination half-life after dose of COVID-HIGIV [Day 1 through Day 85]
The apparent terminal elimination half-life after dose of COVID-HIGIV.
Pharmacokinetics parameter of systemic clearance after dose of COVID-HIGIV [Day 1 through Day 85]
The systemic clearance after dose of COVID-HIGIV.
Pharmacokinetics parameter of volume of distribution after dose of COVID-HIGIV [Day 1 through Day 85]
The volume of distribution after dose of COVID-HIGIV.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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/m2.
Women who are either:

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
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., RT-PCR negative for SARS-CoV-2 and negative for SARS-CoV-2 antibodies) at Screening.

Exclusion Criteria:

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 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.