Trial Outcomes & Findings for Niclosamide for Mild to Moderate COVID-19 (NCT NCT04399356)

NCT ID: NCT04399356

Last Updated: 2022-04-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

73 participants

Primary outcome timeframe

Reduction in viral shedding as measured by oropharyngeal swab on days, 3, 7, 10, 14.

Results posted on

2022-04-12

Participant Flow

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.

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).

Participant milestones

Participant milestones
Measure
Niclosamide- Experimental Group
Participants received Niclosamide 2 grams by mouth daily for 7 days.
Control Group
Participants received placebo using the same dosing schedule as Experimental Group
Overall Study
STARTED
36
37
Overall Study
COMPLETED
33
34
Overall Study
NOT COMPLETED
3
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Niclosamide- Experimental Group
Participants received Niclosamide 2 grams by mouth daily for 7 days.
Control Group
Participants received placebo using the same dosing schedule as Experimental Group
Overall Study
Lost to Follow-up
1
1
Overall Study
Discontinued Niclosamide/ Placebo
1
2
Overall Study
Withdrawal by Subject
1
0

Baseline Characteristics

Niclosamide for Mild to Moderate COVID-19

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Niclosamide
n=33 Participants
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.
Control
n=34 Participants
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
n=67 Participants
Total of all reporting groups
Age, Continuous
36.82 years
STANDARD_DEVIATION 12.92 • n=5 Participants
35.97 years
STANDARD_DEVIATION 13.27 • n=7 Participants
36.39 years
STANDARD_DEVIATION 13.01 • n=5 Participants
Sex: Female, Male
Female
13 Participants
n=5 Participants
13 Participants
n=7 Participants
26 Participants
n=5 Participants
Sex: Female, Male
Male
20 Participants
n=5 Participants
21 Participants
n=7 Participants
41 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
6 Participants
n=5 Participants
1 Participants
n=7 Participants
7 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
24 Participants
n=5 Participants
32 Participants
n=7 Participants
56 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
3 Participants
n=5 Participants
1 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
3 Participants
n=5 Participants
2 Participants
n=7 Participants
5 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
White
26 Participants
n=5 Participants
27 Participants
n=7 Participants
53 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
3 Participants
n=5 Participants
1 Participants
n=7 Participants
4 Participants
n=5 Participants
Region of Enrollment
United States
33 participants
n=5 Participants
34 participants
n=7 Participants
67 participants
n=5 Participants

PRIMARY outcome

Timeframe: Reduction in viral shedding as measured by oropharyngeal swab on days, 3, 7, 10, 14.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Niclosamide- Experimental Group
n=33 Participants
Participants received Niclosamide 2 grams by mouth daily for 7 days.
Control Group
n=34 Participants
Participants received placebo using the same dosing schedule as Experimental Group
Time to Respiratory Viral Clearance
3.39 Days
Interval 1.88 to 4.91
3.44 Days
Interval 2.23 to 4.65

SECONDARY outcome

Timeframe: Reduction in fecal viral shedding as measured by fecal PCR on days, 3, 7, 10, 14 and 21.

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Niclosamide- Experimental Group
n=33 Participants
Participants received Niclosamide 2 grams by mouth daily for 7 days.
Control Group
n=34 Participants
Participants received placebo using the same dosing schedule as Experimental Group
Time to Fecal Viral Clearance
6.12 Days
Interval 3.51 to 8.73
5.77 Days
Interval 3.3 to 8.23

SECONDARY outcome

Timeframe: Day 1- 30

Population: Progression to Severe COVID

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.

Outcome measures

Outcome measures
Measure
Niclosamide- Experimental Group
n=33 Participants
Participants received Niclosamide 2 grams by mouth daily for 7 days.
Control Group
n=34 Participants
Participants received placebo using the same dosing schedule as Experimental Group
Number of Participants With Progression to Severe COVID-19 Disease
0 Participants
1 Participants

SECONDARY outcome

Timeframe: Day 1-30

Population: The mean time to resolution of fever \*symptom no longer reported)

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

Outcome measures

Outcome measures
Measure
Niclosamide- Experimental Group
n=33 Participants
Participants received Niclosamide 2 grams by mouth daily for 7 days.
Control Group
n=34 Participants
Participants received placebo using the same dosing schedule as Experimental Group
Number of Days to Resolution of a Fever
10.2 Days
Interval 1.86 to 18.54
3.6 Days
Interval 2.07 to 5.13

Adverse Events

Niclosamide- Experimental Group

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Control Group

Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Niclosamide- Experimental Group
n=33 participants at risk
Participants received Niclosamide 2 grams by mouth daily for 7 days.
Control Group
n=34 participants at risk
Participants received placebo using the same dosing schedule as Experimental Group
Skin and subcutaneous tissue disorders
Skin rash
9.1%
3/33 • 30 days
CTCAE V5.0
8.8%
3/34 • 30 days
CTCAE V5.0
Gastrointestinal disorders
Vomiting
0.00%
0/33 • 30 days
CTCAE V5.0
5.9%
2/34 • 30 days
CTCAE V5.0
Gastrointestinal disorders
Nausea
6.1%
2/33 • 30 days
CTCAE V5.0
20.6%
7/34 • 30 days
CTCAE V5.0

Additional Information

Dorothy Dulko, PhD - Research Project Director

Tufts Medical Center

Phone: (617) 636-5009

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place