Clinical trial NCT04661839: A COVID-19 Study to Evaluate Safety and Pharmacokinetics of COVID-HIGIV Administered in Healthy Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
Keywords: SARS-CoV-2
Coronavirus disease 2019
Severe acute respiratory syndrome coronavirus 2
Immunoglobulins
Immunoglobulins, Intravenous
Antibodies
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
First posted: 2020-12-10
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Subjects With Adverse Events (AEs) up to 3 Days Post-dosing
timeFrame: Day 1 through Day 4
measure: Subjects With Adverse Events That Led to Discontinuation or Temporary Suspension of IV Infusion
timeFrame: 0 hours to 2.5 hours
measure: Subjects With AEs and SAEs After IV Infusion
timeFrame: Day 1 through Day 85
measure: Total Number of AEs and SAEs After IV Infusion
timeFrame: Day 1 through Day 85
measure: 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
timeFrame: Day 1 through Day 85
measure: Pharmacokinetics Parameter of Area Under the Concentration-time (AUC) From Time 0 to Infinity (AUC0-inf) After Dose of COVID-HIGIV
timeFrame: Day 1 through Day 85
measure: Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 14 Days After Dose of COVID-HIGIV
timeFrame: Day 1 through Day 15
measure: Pharmacokinetics Parameter of Area Under the Concentration-time Curve (AUC) From Time 0 to 28 Days (AUC0-28d) After Dose of COVID-HIGIV
timeFrame: Day 1 through Day 29
measure: Pharmacokinetics Parameter of Maximum Observed Concentration (Cmax) of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV
timeFrame: Day 1 through Day 85
measure: Pharmacokinetics Parameter of Time at Which Cmax Occurs After Dose of COVID-HIGIV
timeFrame: Day 1 through Day 85
measure: Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV
timeFrame: Day 1 through Day 29
measure: Pharmacokinetics Parameter of Apparent Terminal Elimination Half-life (T1/2) After Dose of COVID-HIGIV
timeFrame: Day 1 through Day 85
measure: Pharmacokinetics Parameter of Systemic Clearance (CL) After Dose of COVID-HIGIV
timeFrame: Day 1 through Day 85
measure: Pharmacokinetics Parameter of Volume of Distribution (Vz) After Dose of COVID-HIGIV
timeFrame: Day 1 through Day 85
Secondary outcomes:
measure: Body-weight Normalized Pharmacokinetics Parameter of Maximum Observed Concentration of SARS-CoV-2 Antibodies Observed After Dose of COVID-HIGIV
timeFrame: Day 1 through Day 85
measure: 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
timeFrame: Day 1 through Day 85
measure: 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
timeFrame: Day 1 through Day 85
measure: 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
timeFrame: Day 1 through Day 15
measure: 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
timeFrame: Day 1 through Day 29
measure: Body-weight Normalized Pharmacokinetics Parameter of Trough Concentration of SARS-CoV-2 Antibodies Observed 28 Days After Dose (Cmin28d) of COVID-HIGIV
timeFrame: Day 1 through Day 29
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Emergent BioSolutions
name: Chris Cabell, MD, MHS
role: STUDY_DIRECTOR
References: