The Efficacy and Safety of SCTA01 in Hospitalized Patients With Severe COVID-19

Study Overview
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Brief Summary
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The study is a multicenter, adaptive, randomized, double-blinded and placebo-controlled Phase II/III trial, and will be conducted globally. The study is comprised of two parts: dose selection (Phase II) and pivotal treatment effect (Phase III).

Detailed Description
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In this study, Phase II part will evaluate the efficacy, safety and PK of SCTA01 low dose+BSC, high dose+BSC and placebo+BSC in patients with severe COVID-19. In Phase II part, subjects will be randomized at 1:1:1 ratio. At the end of Phase II part, a dose for the Phase III will be determined. The Phase III part will evaluate the efficacy, safety, and immunogenicity of SCTA01 at the recommended dose recommended. Subjects in Phase III part will be randomized at 1:1 ratio to SCTA01+BSC and placebo+BSC groups.

Official Title
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A Multicenter, Adaptive, Randomized, Double-blinded, Placebo-controlled Phase II/III Trial to Evaluate the Efficacy and Safety of Monoclonal Antibody SCTA01 Against SARS-CoV-2 in Hospitalized Patients With Severe COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Drug: SCTA01
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized patients with severe COVID-19 (5 point on NIH 8-point ordinal scale). Male or female adult ≥18 years of age at time of enrollment; Biological samples (not limited to any specific type) collected within 72 hours before randomization is laboratory-confirmed as SARS-CoV-2 infection (PCR or antigen-based diagnostic tests); ≤ 10 days since symptoms of COVID-19 onset. Exclusion Criteria: Patients who need non-invasive ventilation or high flow oxygen (i.e., 6 point on the 8-point ordinal scale); Patients with critical COVID-19; Patients with Severe COVID-19 who received convalescent plasma or COVID-19 vaccine, or anti-SARS-CoV-2 spike (S) protein targeted therapy; Alanine-amino transferase (ALT) or aspartate transaminase (AST) is 5 times higher than the upper limit of the normal value; Estimated glomerular filtration rate (eGFR) <30 mL/min or on dialysis {eGFR calculated by Cockcroft-Gault formula (Cockcroft DW, 1976), Male: CrCL (mL/min) = [(140 - age) × weight (kg)] × 1/ [SCr (mg/dL) × 72]; Female: CrCL (mL/min) = [(140 - age) × weight (kg)] × 0.85/ [SCr (mg/dL) × 72]}.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCTA01 Low Dose+BSC<br>SCTA01in a lower dose+best supportive care | Drug: SCTA01<br>* SCTA01, a recombinant anti-SARS-CoV-2 spike protein monoclonal antibody<br>* Other names: Recombinant anti-SARS-CoV-2 spike protein monoclonal antibody;|
| Experimental: SCTA01 High Dose+BSC<br>SCTA01in a higher dose+best supportive care | Drug: SCTA01<br>* SCTA01, a recombinant anti-SARS-CoV-2 spike protein monoclonal antibody<br>* Other names: Recombinant anti-SARS-CoV-2 spike protein monoclonal antibody;|
| Active Comparator: Placebo+BSC<br>SCTA01 excipients+best supportive care | Other: Placebo<br>* all SCTA01 excipients without active component+best supportive care<br>* Other names: SCTA01 excipients;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The clinical efficacy of SCTA01 (Phase II and III) | As assessed by time to clinical improvement (TTCI) | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of SAEs(Phase II, III) | Cumulative incidence of serious adverse events in both Phase II and III | 3 Months | 
| Change from baseline in viral shedding as measured by RT-qPCR(Phase II and III) | Change from baseline in viral shedding as measured by RT-qPCR in NP swab samples | Day 120 | 
| area under the curve (AUC0-t)(Phase II) | AUC0-t through Day 120 | Day 120 | 
| AUC0-∞(Phase II) | AUC0-∞ through Day 120 | Day 120 | 
| Half-life time (t1/2)(Phase II) | t1/2 through Day 120 | Day 120 | 
| Maximum concentration (Cmax)(Phase II) | Cmax through Day 120 | Day 120 | 
| Peak time (Tmax)(Phase II) | Tmax through Day 120 | Day 120 | 
| Clearance (CL)(Phase II) | CL through Day 120 | Day 120 | 
| Apparent volume of distribution (Vd)(Phase II) | Vd through Day 120 | Day 120 | 
| Elimination rate constant (λz)(Phase II) | λz through Day 120 | Day 120 | 
| Immunogenicity as measured by anti-drug antibodies (ADA) (Phase II, III) | ADA against SCTA01 at baseline and Day 120 | Day 120 |