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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Niclosamide | Active Comparator | 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) |
|
| Control | Placebo Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Niclosamide | Drug | 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. |
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Harry P Selker, MD | Tufts Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35138402 | Result | Cairns DM, Dulko D, Griffiths JK, Golan Y, Cohen T, Trinquart L, Price LL, Beaulac KR, Selker HP. Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19: A Phase 2 Randomized Clinical Trial. JAMA Netw Open. 2022 Feb 1;5(2):e2144942. doi: 10.1001/jamanetworkopen.2021.44942. |
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Of 139 participants were assessed for eligibility, 73 met inclusion criteria and were randomized to treatment (66 participants were excluded: 23 did not meet inclusion criteria, 42 declined participation, 1 co-habited with a previously enrolled participant).
Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Niclosamide- Experimental Group | Participants received Niclosamide 2 grams by mouth daily for 7 days. |
| FG001 | Control Group | Participants received placebo using the same dosing schedule as Experimental Group |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Niclosamide | 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) Niclosamide: 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. Telehealth monitoring: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | We evaluated efficacy of niclosamide in shortening contagious period as determined by time to oropharyngeal viral clearance. Primary analysis was based on ITT population (all randomized participants). The cumulative probability of being in clearance in each randomization group was calculated using the Kaplan-Meier estimator. The cumulative probability of clearance at day 3 between the groups was calculated using a chi-square test based on a log(- log(ยท)) transformation for the survival function. | Posted | Mean | 95% Confidence Interval | Days | Reduction in viral shedding as measured by oropharyngeal swab on days, 3, 7, 10, 14. |
|
30 days
CTCAE V5.0
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Niclosamide- Experimental Group | Participants received Niclosamide 2 grams by mouth daily for 7 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Skin rash | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
There was a precipitous and persistent decrease in the rate of COVID-19 diagnoses in spring and summer 2021 that decreased our enrollment pool. Additionally, as vaccination rates rose, our predetermined exclusion criteria of individuals vaccinated against SARS-CoV-2 limited those available for enrollment.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dorothy Dulko, PhD - Research Project Director | Tufts Medical Center | (617) 636-5009 | ddulko@Tuftsmedicalcenter.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 1, 2021 | Apr 1, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 10, 2021 | Apr 6, 2022 | SAP_002.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D018352 | Coronavirus Infections |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D009534 | Niclosamide |
| ID | Term |
|---|---|
| D012458 | Salicylanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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Double-blinded randomized controlled trial.
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As all members of the Study Team will be blinded, Tufts Investigational Drug Services (IDS) will be unblinded and will dispense both the Niclosamide and placebo. The study intervention (Niclosamide) and placebo will be packaged and as indistinguishable as possible.
|
| Placebo | Drug | The collection of oropharyngeal samples will be observed by a Study Team member via the telehealth platform. |
|
| Telehealth monitoring | Other | 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. |
|
| 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 |
| Withdrawal by Subject |
|
| BG001 | Control | 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) Placebo: The collection of oropharyngeal samples will be observed by a Study Team member via the telehealth platform. Telehealth monitoring: 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Participants received Niclosamide 2 grams by mouth daily for 7 days. |
| OG001 | Control Group | Participants received placebo using the same dosing schedule as Experimental Group |
|
|
| Secondary | 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. | We evaluated efficacy of niclosamide in shortening contagious period as determined by time to fecal viral clearance. Primary analysis was based on ITT population (all randomized participants). The cumulative probability of being in clearance in each randomization group was calculated using the Kaplan-Meier estimator. The cumulative probability of clearance at day 14 between the groups was calculated using a chi-square test based on a log(- log(ยท)) transformation for the survival function. | Posted | Mean | 95% Confidence Interval | Days | Reduction in fecal viral shedding as measured by fecal PCR on days, 3, 7, 10, 14 and 21. |
|
|
|
| Secondary | 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. | Progression to Severe COVID | Posted | Count of Participants | Participants | Day 1- 30 |
|
|
|
| Secondary | Number of Days to Resolution of a Fever | Mean time to fever resolution (symptom no longer reported). | The mean time to resolution of fever *symptom no longer reported) | Posted | Mean | 95% Confidence Interval | Days | Day 1-30 |
|
|
|
| 0 |
| 33 |
| 0 |
| 33 |
| 5 |
| 33 |
| EG001 | Control Group | Participants received placebo using the same dosing schedule as Experimental Group | 0 | 34 | 0 | 34 | 12 | 34 |
| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012457 |
| Salicylamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |