Niclosamide for Mild to Moderate COVID-19
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
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
- 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
- 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.
- 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.
- Number of Days to Resolution of a Fever [Day 1-30]
Mean time to fever resolution (symptom no longer reported).
Eligibility Criteria
Criteria
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.- STUDY00000605
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
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
|
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
|
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%
|
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
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 |
ddulko@Tuftsmedicalcenter.org |
- STUDY00000605