Study of Oral High/Low-dose Cepharanthine Compared With Placebo in Non Hospitalized Adults With COVID-19

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of high/low-dose cepharanthine for the Treatment of COVID-19 in asymptomatic and non-pneumonia mild adult participants with COVID-19 who do not need to be in the hospital, but in alternate care site.

Detailed Description
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Screening participants will sign the appropriate informed consent form (ICF) prior to completion of any study procedures. Patients will be randomized to one of three arms, all participants will receive standardized medical treatment (SMT) according to Scheme for Diagnosis and Treatment of 2019 Novel Coronavirus Pneumonia (The 9th Trial Edition) from health commission of China, including bed rest, adequate energy and nutrition, pay attention to water and electrolyte balance to maintain a stable internal environment, closely monitor and Chinese traditional medicine, etc. low-dose experimental arm：cepharanthine 60mg/day + SMT high-dose experimental arm：cepharanthine 120mg/day + SMT placebo control arm：placebo + SMT The primary outcome measure is the time to viral clearance which defined as first positive nucleic acid test to the date of the first negative test (in two consecutive point). SARS-CoV-2 viral load was detected and quantified by RT-PCR using nasopharyngeal swabs . Ct value>35 for both ORF1ab and N gene was considered as negativity.

Official Title
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An Interventional Efficacy and Safety, Phase 2, Double-blind, 3-arm Study to Investigate Orally Administered High/Low-dose Cepharanthine Compared With Placebo in Nonhospitalized Asymptomatic or Mild Adult Participants With COVID-19

Conditions
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Asymptomatic COVID-19

Intervention / Treatment
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* Drug: Cepharanthine
* Drug: Cepharanthine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged over 16 years old with all genders SARS-CoV-2 positive（laboratory-confirmed reverse transcription polymerase chain reaction (RT PCR) test) patient or immediate adult family member agrees to participate in this study and signs an informed consent form asymptomatic or patients with mild covid-19 symptoms confirmed SARS-CoV-2 infection within 5 days prior to randomization Exclusion Criteria: Confirmed SARS-CoV-2 infection within > 5 days prior to randomization CT shows pneumonia on admission diagnosed as severe or critical COVID-19 before intervention has a history of chronic underlying disease and acute exacerbation of that underlying disease at the time of admission Females who are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 16 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
Interventional Model Description: Eligible participants with a confirmed diagnosis of SARS-CoV-2 infection in alternate care site will be randomized (1:1:1) to receive low-dose cepharanthine, high-dose cepharanthine or placebo orally every 8 hours for 5 days.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose cepharanthine + standardized medical treatment<br>Drug: cepharanthine (tablet) Day 1 5: 20mg, Q8H X 5 days + standardized medical treatment | Drug: Cepharanthine<br>* Low-dose: Day 1 5: 20mg, Q8H X 5 days (60mg/day)+SMT<br>* Other names: Low- dose Cepharanthine (tablet);|
| Experimental: High-dose cepharanthine + standardized medical treatment<br>Drug: cepharanthine (tablet) Day 1 5: 40mg, Q8H X 5 days + standardized medical treatment | Drug: Cepharanthine<br>* High-dose: Day 1 5: 40mg, Q8H X 5 days (120mg/day) +SMT SMT:standardized medical treatment according to Scheme for Diagnosis and Treatment of 2019 Novel Coronavirus Pneumonia (The 9th Trial Edition) from health commission of China, including bed rest, adequate energy and nutrition, pay attention to water and electrolyte balance to maintain a stable internal environment, closely monitor and Chinese traditional medicine, etc.<br>* Other names: High- dose Cepharanthine (tablet);|
| Placebo Comparator: placebo+standardized medical treatment<br>Drug: cepharanthine placebo (tablet) Day 1 5: placebo + standardized medical treatment | Drug: Placebo<br>* Day 1 5: placebo+SMT SMT:standardized medical treatment according to Scheme for Diagnosis and Treatment of 2019 Novel Coronavirus Pneumonia (The 9th Trial Edition) from health commission of China, including bed rest, adequate energy and nutrition, pay attention to water and electrolyte balance to maintain a stable internal environment, closely monitor, antiviral drug and Chinese medicine treatment, etc.<br>* Other names: Placebo (tablet);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to viral clearance | The time to viral clearance was defined as first positive nucleic acid test（or randomization） to the date of the first negative test (in two consecutive point) | Day 1 through Day 28 | 
| SARS-CoV-2 viral load | SARS-CoV-2 viral load was detected and quantified by RT-PCR using nasopharyngeal swabs . Ct value>35 for both ORF1ab and N gene was considered as negativity. | Day 1 through Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants developing COVID-19 pneumonia |  | Day 1 through Day 28 | 
| Proportion of participants developing severe pneumonia |  | Day 1 through Day 28 | 
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)of CEP relative to placebo. |  | Day 1 through Day 28 | 
| Number of days from the onset of fever until the temperature drops below 37.3°C |  | Day 1 through Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asymptomatic COVID-19, cepharanthine, adult