Niclosamide for Mild to Moderate COVID-19

Sponsor
Tufts Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT04399356
Collaborator
(none)
73
1
2
10.6
6.9

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
73 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Double-blinded randomized controlled trial.Double-blinded randomized controlled trial.
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
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.
Primary Purpose:
Treatment
Official Title:
Niclosamide for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)
Actual Study Start Date :
Oct 1, 2020
Actual Primary Completion Date :
Apr 20, 2021
Actual Study Completion Date :
Aug 19, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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)

Drug: 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.

Other: 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.

Placebo Comparator: 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)

Drug: Placebo
The collection of oropharyngeal samples will be observed by a Study Team member via the telehealth platform.

Other: 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.

Outcome Measures

Primary Outcome Measures

  1. Time to Respiratory Viral Clearance [Reduction in viral shedding as measured by oropharyngeal swab on days, 3, 7, 10, 14.]

    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.

Secondary Outcome Measures

  1. Time to Fecal Viral Clearance [Reduction in fecal viral shedding as measured by fecal PCR on days, 3, 7, 10, 14 and 21.]

    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.

  2. Number of Participants With Progression to Severe COVID-19 Disease [Day 1- 30]

    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.

  3. Number of Days to Resolution of a Fever [Day 1-30]

    Mean time to fever resolution (symptom no longer reported).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Tufts Medical Center Boston Massachusetts United States 02111

Sponsors and Collaborators

  • Tufts Medical Center

Investigators

  • Principal Investigator: Harry P Selker, MD, Tufts Medical Center

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT04399356
Other Study ID Numbers:
  • STUDY00000605
First Posted:
May 22, 2020
Last Update Posted:
Apr 12, 2022
Last Verified:
Apr 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by Tufts Medical Center
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details 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.
Pre-assignment Detail 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).
Arm/Group Title Niclosamide- Experimental Group Control Group
Arm/Group Description Participants received Niclosamide 2 grams by mouth daily for 7 days. Participants received placebo using the same dosing schedule as Experimental Group
Period Title: Overall Study
STARTED 36 37
COMPLETED 33 34
NOT COMPLETED 3 3

Baseline Characteristics

Arm/Group Title Niclosamide Control Total
Arm/Group Description 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. 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. Total of all reporting groups
Overall Participants 33 34 67
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
36.82
(12.92)
35.97
(13.27)
36.39
(13.01)
Sex: Female, Male (Count of Participants)
Female
13
39.4%
13
38.2%
26
38.8%
Male
20
60.6%
21
61.8%
41
61.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
6
18.2%
1
2.9%
7
10.4%
Not Hispanic or Latino
24
72.7%
32
94.1%
56
83.6%
Unknown or Not Reported
3
9.1%
1
2.9%
4
6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
3
9.1%
2
5.9%
5
7.5%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
1
3%
3
8.8%
4
6%
White
26
78.8%
27
79.4%
53
79.1%
More than one race
0
0%
1
2.9%
1
1.5%
Unknown or Not Reported
3
9.1%
1
2.9%
4
6%
Region of Enrollment (participants) [Number]
United States
33
100%
34
100%
67
100%

Outcome Measures

1. Primary Outcome
Title Time to Respiratory Viral Clearance
Description 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.
Time Frame Reduction in viral shedding as measured by oropharyngeal swab on days, 3, 7, 10, 14.

Outcome Measure Data

Analysis Population Description
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(·)) transformation for the survival function.
Arm/Group Title Niclosamide- Experimental Group Control Group
Arm/Group Description Participants received Niclosamide 2 grams by mouth daily for 7 days. Participants received placebo using the same dosing schedule as Experimental Group
Measure Participants 33 34
Mean (95% Confidence Interval) [Days]
3.39
3.44
2. Secondary Outcome
Title Time to Fecal Viral Clearance
Description 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.
Time Frame Reduction in fecal viral shedding as measured by fecal PCR on days, 3, 7, 10, 14 and 21.

Outcome Measure Data

Analysis Population Description
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(·)) transformation for the survival function.
Arm/Group Title Niclosamide- Experimental Group Control Group
Arm/Group Description Participants received Niclosamide 2 grams by mouth daily for 7 days. Participants received placebo using the same dosing schedule as Experimental Group
Measure Participants 33 34
Mean (95% Confidence Interval) [Days]
6.12
5.77
3. Secondary Outcome
Title Number of Participants With Progression to Severe COVID-19 Disease
Description 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.
Time Frame Day 1- 30

Outcome Measure Data

Analysis Population Description
Progression to Severe COVID
Arm/Group Title Niclosamide- Experimental Group Control Group
Arm/Group Description Participants received Niclosamide 2 grams by mouth daily for 7 days. Participants received placebo using the same dosing schedule as Experimental Group
Measure Participants 33 34
Count of Participants [Participants]
0
0%
1
2.9%
4. Secondary Outcome
Title Number of Days to Resolution of a Fever
Description Mean time to fever resolution (symptom no longer reported).
Time Frame Day 1-30

Outcome Measure Data

Analysis Population Description
The mean time to resolution of fever *symptom no longer reported)
Arm/Group Title Niclosamide- Experimental Group Control Group
Arm/Group Description Participants received Niclosamide 2 grams by mouth daily for 7 days. Participants received placebo using the same dosing schedule as Experimental Group
Measure Participants 33 34
Mean (95% Confidence Interval) [Days]
10.2
3.6

Adverse Events

Time Frame 30 days
Adverse Event Reporting Description CTCAE V5.0
Arm/Group Title Niclosamide- Experimental Group Control Group
Arm/Group Description Participants received Niclosamide 2 grams by mouth daily for 7 days. Participants received placebo using the same dosing schedule as Experimental Group
All Cause Mortality
Niclosamide- Experimental Group Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/33 (0%) 0/34 (0%)
Serious Adverse Events
Niclosamide- Experimental Group Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/33 (0%) 0/34 (0%)
Other (Not Including Serious) Adverse Events
Niclosamide- Experimental Group Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 5/33 (15.2%) 12/34 (35.3%)
Gastrointestinal disorders
Vomiting 0/33 (0%) 2/34 (5.9%)
Nausea 2/33 (6.1%) 7/34 (20.6%)
Skin and subcutaneous tissue disorders
Skin rash 3/33 (9.1%) 3/34 (8.8%)

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dorothy Dulko, PhD - Research Project Director
Organization Tufts Medical Center
Phone (617) 636-5009
Email ddulko@Tuftsmedicalcenter.org
Responsible Party:
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT04399356
Other Study ID Numbers:
  • STUDY00000605
First Posted:
May 22, 2020
Last Update Posted:
Apr 12, 2022
Last Verified:
Apr 1, 2022