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

NCT04661839 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: EBS-CVH-003
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Keywords

SARS-CoV-2; Coronavirus disease 2019; Severe acute respiratory syndrome coronavirus 2; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies

Outcome Measures

Primary Outcomes (14)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Day 1 through Day 85

Secondary Outcomes (6)

• 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

Study Arms (4)

COVID-HIGIV Dose Level 1 (100 mg/kg)

EXPERIMENTAL

Eligible subjects randomized to receive a single IV infusion of COVID-HIGIV dose level 1 (100 mg/kg).

Biological: COVID-HIGIV

COVID-HIGIV Dose Level 2 (200 mg/kg)

EXPERIMENTAL

Eligible subjects randomized to receive a single IV infusion of COVID-HIGIV dose level 2 (200 mg/kg).

Biological: COVID-HIGIV

COVID-HIGIV Dose Level 3 (400 mg/kg)

EXPERIMENTAL

Eligible subjects randomized to receive a single IV infusion of COVID-HIGIV dose level 3 (400 mg/kg).

Biological: COVID-HIGIV

Dose Placebo (saline)

PLACEBO COMPARATOR

Eligible subjects randomized to receive a single IV infusion of saline placebo.

Other: Placebo (saline)

Interventions

COVID-HIGIV BIOLOGICAL

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.

Also known as: NP-028

COVID-HIGIV Dose Level 1 (100 mg/kg); COVID-HIGIV Dose Level 2 (200 mg/kg); COVID-HIGIV Dose Level 3 (400 mg/kg)

Placebo (saline) OTHER

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.

Dose Placebo (saline)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Emergent BioSolutions: lead
• United States Department of Defense: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• Liu STH, Mirceta M, Lin G, Anderson DM, Broomes T, Jen A, Abid A, Reich D, Hall C, Aberg JA. Safety, Tolerability, and Pharmacokinetics of Anti-SARS-CoV-2 Immunoglobulin Intravenous (Human) Investigational Product (COVID-HIGIV) in Healthy Adults: a Randomized, Controlled, Double-Blinded, Phase 1 Study. Antimicrob Agents Chemother. 2023 Mar 16;67(3):e0151422. doi: 10.1128/aac.01514-22. Epub 2023 Feb 28.

  PMID: 36852998 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Clinical Development Representative
• Organization: Emergent BioSolutions Canada Inc.

ctgov@ebsi.com

204-275-4074

Study Officials

• Chris Cabell, MD, MHS

  Emergent BioSolutions

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: December 10, 2020
• Study Start: December 24, 2020
• Primary Completion: July 27, 2021
• Study Completion: July 27, 2021
• Last Updated: June 8, 2025
• Results First Posted: February 2, 2023

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: By April 2025 for up to 2 years

Locations

US (1)