Niclosamide for Mild to Moderate COVID-19

Study Overview
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Brief Summary
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This study will evaluate the antihelmintic drug, Niclosamide, as a potential treatment for mild to moderate coronavirus disease 2019 (COVID-19).

Detailed Description
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Niclosamide, which has potent antiviral activity against single-stranded RNA viruses including coronaviruses, was proposed as an antiviral during the Severe Acute Respiratory Syndrome (SARS) outbreak in 2002 and has activity including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) where it was found to inhibit SARS coronavirus, SARS-CoV, in in vitro studies and similarly structured RNA viruses (both in vitro and in vivo). The investigators hypothesize that the antiviral activity of Niclosamide may be extended to COVID-19.

Official Title
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Niclosamide for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Niclosamide
* Drug: Placebo
* Other: Telehealth monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive SARS-CoV-2 test by PCR No requirement of oxygen supplementation Ability to take oral medication Exclusion Criteria: Known allergic reactions to any components of Niclosamide medication Participation in another trial or use of any experimental treatment for COVID-19, including chloroquine, hydroxychloroquine, remdesivir, and lopinavir/ritonavir Hospitalization or requirement of hospitalization at the time of enrollment

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
Interventional Model Description: Double-blinded randomized controlled trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Niclosamide<br>Participants in the treatment arm will receive Niclosamide 2 grams orally on day 1 and daily for 6 more days (total 7 days of treatment) | Drug: Niclosamide<br>* Participants in the treatment arm will receive Niclosamide 2 grams orally once daily for 7 days in addition to current standard of care treatment. Oropharyngeal swab samples will be collected for viral shedding as measured by PCR on days 3, 7, 10, 14. Fecal samples will be collected for viral shedding as measured by PCR on days 3, 7, 10, 14, 21. A baseline fecal and oropharyngeal sample will be obtained on Day 1 prior to starting dosing of Niclosamide/ placebo.<br>Other: Telehealth monitoring<br>* In addition to Niclosamide or placebo treatments, all enrolled patients will be provided a home thermometer as well as a fingertip probe pulse oximeter, with the specific instructions to monitor both temperature at oxygen saturation at the time of daily oral administration of drug. The collection of oropharyngeal samples will be directly observed by a Study Team member via the telehealth platform.<br>|
| Placebo Comparator: Control<br>Participants in the control group will receive identical-appearing placebo by mouth in the same numbers of pills on day 1 and daily for 6 more days (total 7 days of treatment) | Drug: Placebo<br>* The collection of oropharyngeal samples will be observed by a Study Team member via the telehealth platform.<br>Other: Telehealth monitoring<br>* In addition to Niclosamide or placebo treatments, all enrolled patients will be provided a home thermometer as well as a fingertip probe pulse oximeter, with the specific instructions to monitor both temperature at oxygen saturation at the time of daily oral administration of drug. The collection of oropharyngeal samples will be directly observed by a Study Team member via the telehealth platform.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Respiratory Viral Clearance | Respiratory viral clearance is defined as the first day a participant's oropharyngeal (oral) sample result is negative, provided that none of the subsequent oral sample results are positive. We will calculate the time to clearance since Day 1. | Reduction in viral shedding as measured by oropharyngeal swab on days, 3, 7, 10, 14. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Fecal Viral Clearance | Reduction in fecal viral shedding as measured by fecal PCR on days, 3, 7, 10, 14 and 21. Fecal viral clearance is defined as the first day a participant's fecal sample result is negative, provided that none of the subsequent fecal sample results are positive; calculated as the time to clearance since Day 1. | Reduction in fecal viral shedding as measured by fecal PCR on days, 3, 7, 10, 14 and 21. | 
| Number of Participants With Progression to Severe COVID-19 Disease | Defined as 1) O2 saturation <92% on room air (in two consecutive measurements at least 2 hours apart) OR 2) requirement of hospitalization OR 3) need for artificial ventilation OR 4) death. 1) We will compare the proportion of participants who progressed to severe COVID disease between groups. | Day 1- 30 | 
| Number of Days to Resolution of a Fever | Mean time to fever resolution (symptom no longer reported). | Day 1-30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Coronavirus, Treatment, Pill, Telehealth, Viral shedding