A Phase 1/2 Study to Assess the Safety, Tolerability and Pharmacokinetics of NGM621 in Healthy Subjects, and to Assess the Safety, PK and Efficacy in Subjects With Moderate to Severe ARDS Caused by COVID-19

Study Overview
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Brief Summary
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This study is a combined Phase 1 and Phase 2 study with IV infusion of NGM621 to evaluate the safety, tolerability, and PK in healthy volunteers (Part 1), and safety, tolerability, PK and efficacy in subjects with confirmed SARS-CoV-2 infection (Part 2).

Official Title
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A Randomized, Double Blind, Placebo Controlled, Combined Phase 1/2 Single Dose and Multiple Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of NGM621 in Healthy Volunteers and the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Subjects With Confirmed SARS-CoV-2 Infection

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: NGM621
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects of childbearing potential must have a negative serum pregnancy test result at Screening and a negative urine pregnancy test result prior to dosing. Female subjects of childbearing potential and male subjects with a female partner of childbearing potential must use an effective method of contraception during the study, for at least 1 month following study completion, and must not plan to become pregnant for at least 1 month after her last study medication dose. BMI 18-32 kg/m2 inclusive Ability to understand and provide informed consent Subjects confirmed with SARS-CoV-2 infection by PCR and hospitalized If on mechanical support, less or equal than 2 days on mechanical ventilation or oxygenation Exclusion Criteria: Currently enrolled in another investigational protocol to treat SARS-CoV-2 infection Known history of complement deficiency Active infection with, or history of, compllicated pneumococcal or Neisseria meningitis infection or history of unexplained, recurrent infection, within the last 60 days prior to dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 Dose Level 1 - Active<br> | Biological: NGM621<br>* NGM621 will be administered via IV infusion<br>|
| Placebo Comparator: Part 1 Dose Level 1 - Placebo<br> | Biological: Placebo<br>* Placebo will be administered via IV infusion<br>|
| Experimental: Part 1 Dose Level 2 - Active<br> | Biological: NGM621<br>* NGM621 will be administered via IV infusion<br>|
| Placebo Comparator: Part 1 Dose Level 2 - Placebo<br> | Biological: Placebo<br>* Placebo will be administered via IV infusion<br>|
| Active Comparator: Part 2 Multi-Dose Level 1 - Active<br> | Biological: NGM621<br>* NGM621 will be administered via IV infusion<br>|
| Placebo Comparator: Part 2 Multi-Dose Level 1 - Placebo<br> | Biological: Placebo<br>* Placebo will be administered via IV infusion<br>|
| Active Comparator: Part 2 Multi-Dose Level 2 - Active<br> | Biological: NGM621<br>* NGM621 will be administered via IV infusion<br>|
| Placebo Comparator: Part 2 Multi-Dose Level 2 - Placebo<br> | Biological: Placebo<br>* Placebo will be administered via IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent adverse events - Part 1 | TEAEs in subjects receiving NGM621 compared to placebo | 85 days | 
| Treatment emergent adverse events - Part 2 | TEAEs in subjects receiving NGM621 compared to placebo | 91 days | 
| Clinical status at Day 15 and Day 29 - Part 2 | Clnical status (on an 8-point ordinal scale) in NGM621 group versus placebo group | 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maxiumum Serum Concentration [Cmax] |  | 91 days | 
| Mortality at Day 29 |  | 29 days | 
| Duration of Supplemental Oxygen Requirement |  | 91 days | 
| Change in Hemolytic Assays (CH50 and AH50) from Baseline |  | 91 days |