A COVID-19 Study to Evaluate Safety and PK of COVID-HIG Administered Through IM, SC, or IV Routes as a Single Dose Regimen to SARS-CoV-2 Uninfected Adults

Study Overview
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Brief Summary
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It is hypothesized that COVID-HIG in all three routes of administration (intramuscular [IM], subcutaneous [SC], and intravenous [IV]) is well-tolerated and that concentrations of SARS-CoV-2 antibodies will be measurable over time, with derived pharmacokinetic (PK) parameters in line with immunoglobulin product class kinetics.

Detailed Description
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This will be a Phase 1, two-center, open-label, randomized study to evaluate one dose level of COVID-HIG administered IM or SC for safety and PK in healthy adults compared to COVID-HIG administered intravenously. Approximately 36 adult participants will be targeted to be enrolled in the study. Enrollment into the study will be staggered, wherein no more than three participants will be randomized and dosed on the first day with at least one hour between dosing of each participant. On the second day, up to two more subjects will be randomized and dosed. The remaining participants will be randomized and dosed, with no more than 5 participants dosed per day. Safety data will be reviewed by a Safety Monitoring Committee (SMC) (consisting of at least three independent external members) after all 12 participants in Cohort 1 have completed at least 72 hours of safety follow-up. An overall decision by the SMC will be made whether to proceed with full randomization (1:1:1) and dosing of the remaining study participants (Cohort 2, n=24). Participants will be stratified based on their SARS-CoV-2 antibody status (positive/negative) at screening. Study enrollment and administration of study treatments may be paused by the PI or medical monitor for safety review by the SMC if any of the following occur after study product administration and during the enrollment period: One or more serious adverse event(s) [SAE(s)]. Three or more of the same Grade 3 adverse events (AEs) Three or more Grade 2 hypersensitivity AEs If any participants become positive for SARS-CoV-2 during the study follow-up period, they will be assessed using an Ordinal Outcome Scale until symptom resolution and will be followed until they complete their last scheduled follow-up visit. Participants who test positive for SARS-CoV-2 will be excluded from PK analyses.

Official Title
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A Phase 1, Open-Label, Randomized Study to Evaluate Safety and Pharmacokinetics of Anti-SARS-CoV-2 Immunoglobulin (Human) Investigational Product (COVID-HIG) Administered Through Intramuscular, Subcutaneous or Intravenous Routes as a Single Dose Regimen to SARS-CoV-2 Uninfected Adults

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: COVID-HIG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide written informed consent (voluntarily signed by the participant) prior to performing study procedures. Females and males 18-59 years of age. Have a body mass index (BMI) less than or equal to 35.0 kg/m^2 Healthy, based on medical history (no chronic disease, no chronic therapy, no ongoing acute condition within four weeks prior to dosing), normal physical examination (no clinically significant findings in the opinion of the investigator), and screening laboratory assessments (no clinically significant findings in the opinion of the investigator). No clinical symptoms suspicious for COVID-19 infection, as well as SARS-CoV-2 Immunoglobulin M (IgM) antibody negative and no laboratory evidence of current SARS-CoV-2 infection (i.e., reverse transcription polymerase chain reaction (RT-PCR) negative for SARS-CoV-2) at Screening. Females must not be pregnant, or trying to become pregnant as demonstrated by either of the following A or B: A. Not of childbearing potential: surgically sterile (at least six weeks post bilateral salpingectomy, bilateral oophorectomy, or hysterectomy); or post-menopausal (history of ≥12 consecutive months without menses prior to randomization in the absence of other pathologic or physiologic causes and confirmed by follicle stimulating hormone [FSH] level ≥40 mIU/mL) OR B. Women of childbearing potential who are not planning to be pregnant during the study period who meet all of criteria i-iii: i. Negative serum pregnancy test at the Screening Visit. ii. Negative urine pregnancy test on Day 1 (a positive test will result in discontinuation from intervention). iii. Using one of the following highly effective methods of contraception during the study: Combined estrogen and progestogen, or progestogen-only hormonal contraception associated with inhibition of ovulation (e.g., implants, pills, patches) initiated ≥30 days prior to Study Day 1. Intrauterine device (IUD) or hormone releasing intrauterine system (IUS) inserted ≥30 days prior to Study Day 1. Participant understands and agrees to comply with planned study procedures. Exclusion Criteria: Use of any investigational product within 30 days or SARS-CoV-2 monoclonal antibodies and COVID-19 convalescent plasma within 90 days prior to Screening or anticipated receipt during the study follow-up period, or participant plans to participate in another clinic study during the study period. Receipt of 1 or 2 doses COVID-19 vaccine within 60 days prior to screening or during the study follow-up period. SARS-CoV-2 IgG antibody levels >80 AU/mL as determined by the Diasorin LIAISON SARS-CoV-2 S1/S2 IgG antibody assay. 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 direct 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. Positive laboratory evidence of current infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV). Note: Positive anti-HCV antibody result along with a negative HCV PCR would NOT be exclusionary. History of allergy or hypersensitivity to blood or plasma products or to COVID-HIG 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 blood loss/donation (>450 mL) within 56 days of 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. Receipt of a live vaccine within 30 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). Any planned elective surgery or procedure during the follow-up period that impacts study compliance. Other condition which may place participant at increased risk due to participation in the study or may impact study compliance as determined by the investigator. An opinion of the investigator (or designee) that it would not be in the best interest of the individual to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be enrolled and assigned equally to one of 3 study arms.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COVID-HIG Intramuscular<br>COVID-HIG single dose administered IM | Biological: COVID-HIG<br>* Anti-SARS-CoV-2 Immunoglobulin (Human) [COVID-HIG] is a purified liquid immunoglobulin G (IgG) preparation<br>* Other names: NP-028;|
| Experimental: COVID-HIG Subcutaneous<br>COVID-HIG single dose administered SC | Biological: COVID-HIG<br>* Anti-SARS-CoV-2 Immunoglobulin (Human) [COVID-HIG] is a purified liquid immunoglobulin G (IgG) preparation<br>* Other names: NP-028;|
| Experimental: COVID-HIG Intravenous<br>COVID-HIG single dose administered IV | Biological: COVID-HIG<br>* Anti-SARS-CoV-2 Immunoglobulin (Human) [COVID-HIG] is a purified liquid immunoglobulin G (IgG) preparation<br>* Other names: NP-028;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events within 72 hours post-dosing | Number of adverse events within 72 hours post-dosing with COVID-HIG | Day 1 to Day 3 | 
| Adverse events leading to discontinuation or temporary suspension of study treatment administration | Number of adverse events leading to discontinuation or temporary suspension of study treatment administration | Day 1 | 
| Adverse events up to 56 days post-administration of a single dose | Number of adverse events up to 56 days post-administration of a single dose of COVID-HIG | Day 0 to Day 57 | 
| Serious adverse events up to 56 days post-administration of a single dose | Number of serious adverse events up to 56 days post-administration of a single dose | Day 0 to Day 57 | 
| Pharmacokinetic parameter of area under the concentration-time curve (AUC) from time 0 to infinity | AUC0-last plus the additional area extrapolated to infinity after dosing | Day 1 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 after COVID-HIG dose. | Day 1 to Day 57 | 
| Pharmacokinetic parameter of maximum observed concentration after dosing (Cmax) | The Cmax after COVID-HIG dosing | Day 1 to Day 57 | 
| Pharmacokinetic parameter of time at (Tmax) which Cmax occurs after dosing | The time at which Cmax occurs after COVID-HIG dosing | Day 1 to Day 57 | 
| Pharmacokinetic parameter of observed or estimated concentration at 28 days (C28d) after dosing | The observed or estimated concentration at 28 days after COVID-HIG dosing | Day 1 to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter of AUC0-inf ratios (bioavailability) compared between routes for comparable dose levels | Area under the concentration-time curve from time 0 to infinity (AUC0-inf) ratios between COVID-HIG SC to IV, IM to IV, and SC to IM | Day 1 to Day 57 | 
| Pharmacokinetic parameter of AUC0-14d after COVID-HIG dosing | Area under the concentration-time curve from time 0 to 14 days after dosing | Day 1 to Day 15 | 
| Pharmacokinetic parameter of AUC0-28d after COVID-HIG dosing | Area under the concentration-time curve from time 0 to 28 days after dosing | Day 1 to Day 29 | 
| Pharmacokinetic parameter of λz (Lambda-z) after COVID-HIG dosing | Terminal elimination rate constant after dosing | Day 1 to Day 57 | 
| Pharmacokinetic parameter of T1/2 (half-life) after COVID-HIG | Apparent terminal elimination half-life after dosing | Day 1 to Day 57 | 
| Pharmacokinetic parameter of CL after COVID-HIG dosing | Systemic clearance (CL) after dosing | Day 1 to Day 57 | 
| Pharmacokinetic parameter of VZ after COVID-HIG dosing | Volume of distribution (VZ) after dosing | Day 1 to Day 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Coronavirus disease 2019, Severe acute respiratory syndrome coronavirus 2, immunoglobulins, intravenous, subcutaneous, intramuscular