NCT04858425: RESERVOIR

Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection

Terminated Phase 2 Results posted Last updated 8 October 2024

What this trial tests

Phase 2 trial testing Niclosamide in Covid19 in 166 participants. Terminated before completion.

Timeline

30 April 2021

Primary endpoint
4 June 2022

10 September 2023

Quick facts

Lead sponsor	Entero Therapeutics
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	166
Start date	30 April 2021
Primary completion	4 June 2022
Estimated completion	10 September 2023
Sites	25 locations across United States, Ukraine, India

Drugs / interventions tested

• Niclosamide — full drug profile →
• Placebo

Conditions studied

• Covid19 — all drugs for Covid19 →

Sponsor

Entero Therapeutics — full company profile →

Who can join

18 and older, any sex, with Covid19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

SAEs Primary · Day 1 to 6 weeks

Serious adverse event (SAE) coded by System Organ Class (SOC) and Preferred Term (PT), using the Medical Dictionary for Regulatory Activities (MedDRA).

Infections and infestations

Group	Value	95% CI
Niclosamide	0
Placebo	1

Injury, poisoning and procedural complications

Group	Value	95% CI
Niclosamide	0
Placebo	1

TEAE Primary · Day 1 to 6 weeks

Proportion of patients with Treatment Emergent Adverse Events (TEAE) leading to study drug discontinuation.

Gastrointetinal disorders

Group	Value	95% CI
Niclosamide	1
Placebo	1

Blood and lymphatic system disorders

Group	Value	95% CI
Niclosamide	0
Placebo	1

Endocrine disorders

Group	Value	95% CI
Niclosamide	0
Placebo	1

Infections and infestations

Group	Value	95% CI
Niclosamide	0
Placebo	1

Injury, poisoning and procedural complications

Group	Value	95% CI
Niclosamide	0
Placebo	1

Investigations

Group	Value	95% CI
Niclosamide	1
Placebo	1

Musculoskeletal and connective tissue disorders

Group	Value	95% CI
Niclosamide	0
Placebo	1

Fecal RNA Virus Clearance Primary · Day 1 to 6 weeks

Time to fecal viral RNA clearance (stool sample) assessed by RT-qPCR in the niclosamide arm compared to the placebo arm.

Day 4

Group	Value	95% CI
Niclosamide	8
Placebo	9

Day 8

Group	Value	95% CI
Niclosamide	21
Placebo	20

Day 15

Group	Value	95% CI
Niclosamide	40
Placebo	33

Day 22

Group	Value	95% CI
Niclosamide	48
Placebo	42

Day 29

Group	Value	95% CI
Niclosamide	51
Placebo	43

Day 36

Group	Value	95% CI
Niclosamide	51
Placebo	45

Day 43

Group	Value	95% CI
Niclosamide	52
Placebo	48

Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Leukocytes and Platelets) Primary · Day 1 to Day 43

Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided.

Leukocytes

Group	Value	95% CI
Niclosamide	0.340	-12.71 – 4.38
Placebo	0.495	-11.13 – 5.70

Platelets

Group	Value	95% CI
Niclosamide	11.5	-196 – 116
Placebo	3.0	-337 – 148

Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Erythrocytes) Primary · Day 1 to Day 43

Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Erythrocytes

Group	Value	95% CI
Niclosamide	-0.250	-0.87 – .85
Placebo	-0.125	-0.96 – 0.84

Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemocrit) Primary · Day 1 to Day 43

Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Hemocrit (L/L)

Group	Value	95% CI
Niclosamide	-0.0195	-0.100 – 0.077
Placebo	-0.0130	-0.141 – 0.072

Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemoglobin) Primary · Day 1 to Day 43

Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Hemoglobin (g/L)

Group	Value	95% CI
Niclosamide	-4.0	-30 – 13
Placebo	-2.5	-39 – 14

Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Corpuscular Volume) Primary · Day 1 to Day 43

Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided. Corpuscular volume (fL)

Group	Value	95% CI
Niclosamide	-0.35	-10.5 – 9.3
Placebo	-0.75	-16.1 – 15.8

Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium) Primary · Day 1 to Day 43

Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided.

BUN

Group	Value	95% CI
Niclosamide	0.000	-6.07 – 4.65
Placebo	0.000	-8.21 – 3.21

Glucose

Group	Value	95% CI
Niclosamide	-0.360	-5.22 – 3.28
Placebo	0.110	-9.15 – 3.28

Chloride

Group	Value	95% CI
Niclosamide	2.0	-7 – 9
Placebo	1.0	-9 – 13

Potassium

Group	Value	95% CI
Niclosamide	0.00	-1.0 – 1.1
Placebo	0.10	-1.9 – 2.1

Sodium

Group	Value	95% CI
Niclosamide	1.0	-6 – 7
Placebo	0.0	-13 – 7

Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH) Primary · Day 1 to Day 43

Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided.

Alkaline Phosphatase

Group	Value	95% CI
Niclosamide	2.0	-173 – 26
Placebo	2.0	-76 – 49

AST

Group	Value	95% CI
Niclosamide	-2.5	-117 – 98
Placebo	-1.0	-151 – 26

ALT

Group	Value	95% CI
Niclosamide	-3.0	-70 – 73
Placebo	-4.0	-77 – 32

LDH

Group	Value	95% CI
Niclosamide	-2.0	-209 – 157
Placebo	6.0	-86 – 102

Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Bilirubin and Serum Creatinine) Primary · Day 1 to Day 43

Change in safety laboratory tests, including CBC, BUN, blood sugar, electrolytes, alkaline phosphatase, AST, ALT, LDH, total bilirubin, serum creatinine, from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided.

Bilirubin

Group	Value	95% CI
Niclosamide	0.60	-10.7 – 10.1
Placebo	1.20	-4.3 – 22

Creatinine

Group	Value	95% CI
Niclosamide	0.0	-53 – 44
Placebo	0.0	-44 – 27

Adverse events — posted to ClinicalTrials.gov

Time frame: 6 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Niclosamide

Serious: 0/84 (0%)

Deaths: 0/84

Placebo

Serious: 2/82 (2%)

Deaths: 0/82

Serious adverse events (2 terms)

Reaction	System	Niclosamide	Placebo
Infections and infestations	Infections and infestations	—	—
Injury, poisoning and procedural complications	Injury, poisoning and procedural complications	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	Niclosamide	Placebo
Gastrointestinal disorders	Gastrointestinal disorders	—	—
Blood and lymphatic system disorders	Blood and lymphatic system disorders	—	—
Endocrine disorders	Endocrine disorders	—	—
Infections and infestations	Infections and infestations	—	—
Injury, poisoning and procedural complications	Injury, poisoning and procedural complications	—	—
Investigations	Investigations	—	—
Musculoskeletal and connective tissue disorders	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: Infections and infestations, Injury, poisoning and procedural complications.

Data from ClinicalTrials.gov NCT04858425 adverse events section.

Sponsor's own description

This is a 2-part, 2-arm, Phase 2 , multicentre, randomized, double-blind, placebo-controlled study in adults with COVID-19 with gastrointestinal infection.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Niclosamide-A promising treatment for COVID-19.
   Singh S, Weiss A, Goodman J, Fisk M, et al · · 2022 · cited 64× · PMID 35348204 · DOI 10.1111/bph.15843
2. Know your enemy and know yourself - the case of SARS-CoV-2 host factors.
   Lee WS, Yousefi M, Yan B, Yong CL, et al · · 2021 · cited 10× · PMID 34488003 · DOI 10.1016/j.coviro.2021.08.007
3. Gastrointestinal inflammation and cancer: viral and bacterial interplay.
   Arrè V, De Luca R, Mrmić S, Marotta S, et al · · 2025 · cited 5× · PMID 40568785 · DOI 10.1080/19490976.2025.2519703