To Evaluate SSD8432/ Ritonavir in Adults With COVID-19

Study Overview
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Brief Summary
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This is a randomized, double-blind, Phase 1b clinical trial to evaluate the safety, Pharmacodynamics, and Pharmacokinetic of SSD8432 combined with ritonavir tablets in adults with COVID-19.

Detailed Description
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This is a randomized, double-blinded, placebo-controlled, dose-climbing Phase Ib clinical trial, designed to evaluate the safety, pharmacodynamics, and pharmacokinetics of SSD8432/ ritonavir versus placebo in asymptomatic, mild, and common type adult COVID-19 subjects. This clinical trial is planned to enroll 32 asymptomatic infected, mild or common type adult COVID-19 subjects, divided into 2 cohorts according to different doses of SSD8432: Cohort 1: 16 subjects, 12 subjects will receive low-dose SSD8432/ ritonavir, and 4 subjects received placebo; Cohort 2: 16 subjects, 12 subjects will receive high-dose SSD8432/ ritonavir, and 4 subjects received placebo.

Official Title
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Randomized, Double-blind, Phase Ib Clinical Trial to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetic of SSD8432/ Ritonavir Multiple Doses in Treatment of Adults With Asymptomatic Infection, Mild, and Common Type of COVID-19

Conditions
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COVID-19 Patients

Intervention / Treatment
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* Drug: SSD8432 dose 1/Ritonavir
* Drug: SSD8432 dose 2/Ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and ≤75, male or female. Asymptomatic Infection, Mild, or Common Type of COVID-19. Initial positive test of SARS-Cov-2 within 5 days of randomization. Initial onset of COVID-19 signs/symptoms within 3 days of randomization. The Ct value of SARS-COV-2 nucleic acid test before randomization is ≤ 25, or the Ct value is >25 and sarS-COV-2 serum IgG and IgM are negative. Exclusion Criteria: Transnasal high-flow oxygen therapy or non-invasive ventilation, invasive mechanical ventilation, or ECMO is required or anticipated to be urgently required. Prior to current disease episode, any confirmed SARS-CoV-2 infection. Known medical history of active liver disease (other than nonalcoholic hepatic steatosis). Receiving dialysis or have known moderate to severe renal impairment. Known human immunodeficiency virus (HIV) infection. Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention.s. Oxygen saturation of ≤ 93% on room air obtained at rest within 24 hours prior to randomization.. Treatment with antivirals against SARS-CoV-2 within 14 days. Current or expected use of any medications or substances that are highly dependent on CYP3A4 for clearance. Concomitant use of any medications or substances that are strong inducers of CYP3A4 are prohibited within 28 days. Has received or is expected to receive COVID-19 monoclonal antibody, convalescent COVID-19 plasma or other prohibited concomitant medication. Females who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: SSD8432 dose 1<br>SSD8432 dose 1/ritonavir or placebo | Drug: SSD8432 dose 1/Ritonavir<br>* Cohort 1:SSD8432/ritonavir or placebo, on day 1  day5，BID；<br>* Other names: SIM0417 dose 1/Ritonavir;|
| Experimental: SSD8432 dose 2<br>SSD8432 dose 2/ritonavir or placebo | Drug: SSD8432 dose 2/Ritonavir<br>* Cohort 2:SSD8432/ritonavir or placebo, on day 1  day5，BID；<br>* Other names: SIM0417 dose 2/Ritonavir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Frequency of TEAE | Baseline through Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral load | Changes of viral load compared to the baseline | Baseline through Day 28 | 
| Time to Sustained Alleviation | Time to Sustained Alleviation of Targeted COVID-19 Signs/Symptoms | Baseline through Day 28 | 
| Proportion of Participants Progressing to a Worsening Status (higher score) | WHO clinical progression scale (0 to 10) | Baseline through Day 28 | 
| Maximum Plasma Concentration [Cmax] | Plasma Concentration of SSD8432 | Baseline through Day 5 | 
| Area Under the Plasma concentration-time Curve [AUC] | Plasma Concentration of SSD8432 | Baseline through Day 5 |