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

A 2-Part, 2-Arm, Phase 2, Randomized, Double-Blind, Placebo-Controlled Study on the Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection

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

Study Overview

• Status: Terminated
• Conditions: Covid19
• Intervention / Treatment: Drug: Niclosamide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Andhra Pradesh
    • Secunderabad, Andhra Pradesh, India, 50003
      • Yashoda Hospital
  • Gujarat
    • Vadodara, Gujarat, India, 390001
      • SSG Hospital and Medical Institute
    • Vadodara, Gujarat, India, 390021
      • GMERS Medical College and Hospital
  • Maharashtra
    • Pune, Maharashtra, India, 411013
      • Noble Hospital Private Limited
  • New Delhi
    • Nagar, New Delhi, India, 110060
      • Sir Ganga Ram Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India, 302039
      • Maharaja Agrasen Superspeciality Hospital, Jaipur
  • Telangana
    • Hyderabad, Telangana, India, 500055
      • Malla Reddy Narayana Multispecialty hospital
• Ukraine
  • Dnipro, Ukraine, 41102
    • Municipal Non-profit Enterprise "City Clinical Hospital # 4" of Dnipro City Council
  • Ivano-Frankivsk, Ukraine, 76025
    • Municipal Non-profit Enterprise Central City Clinical Hospital of Ivano-Frankivsk City Council
  • Kharkiv, Ukraine, 61124
    • Municipal Non-Profit Enterprise City Clinical Hospital 13 of Kharkiv Regional Council
  • Kropyvnytskyi, Ukraine, 25006
    • Private Enterprise Private Manufacturing Company Acinus
  • Poltava
    • Kremenchug, Poltava, Ukraine, 39600
      • Communal Non-Commercial Medical Enterprise "Likarnya Prydniprovska"
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Central Alabama Research
  • Florida
    • DeLand, Florida, United States, 32720-0920
      • Midland Florida Clinical Research Center, LLC
    • Hialeah, Florida, United States, 33016-1895
      • New Generation Medical Research
    • Miami, Florida, United States, 33155
      • Miami Clinical Research
    • Miami, Florida, United States, 33126
      • LCC Medical Reserach Institute, LLC
    • Miami, Florida, United States, 33155-2805
      • Westchester General Hospital
    • Miami, Florida, United States, 33175-2912
      • P & S Research, LLC
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Columbus, Georgia, United States, 30076
      • IACT Health - Roswell
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Snake River Research, PLLC
  • Texas
    • Homestead Meadows, Texas, United States, 33032-8225
      • Homestead Associates in Research
    • Mesquite, Texas, United States, 75149
      • SMS Clinical Research LLC
    • Webster, Texas, United States, 77598
      • Tranquil Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Part 1 only, patients with a primary diagnosis of COVID-19, with or without pneumonia, who agree to be monitored daily for at least 7 days after randomization and who accept continuing to be assessed for the study procedures.
2. Part 2 only, patients with a primary diagnosis of COVID-19, with or without pneumonia.

Exclusion Criteria:

1. At the time of randomization, patients who require intensive care unit (ICU) admission or patients with severe respiratory insufficiency who require mechanical ventilation or with rapid worsening of respiratory function leading to expectation for mechanical ventilation or ICU admission.
2. Evidence of rapid clinical deterioration or existence of any life-threatening co-morbidity or any other medical condition that, in the opinion of the investigator, makes the patient unsuitable for inclusion.
3. Patients who, at the time of enrollment, are not in a clinical condition compatible with the oral administration of the study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Niclosamide; Niclosamide tablets 400 mg 3 times daily for 14 days	Drug: Niclosamide; Niclosamide tablets 400 mg 3 times daily for 14 days
Placebo Comparator: Placebo; Matching placebo tablets 3 times daily for 14 days	Drug: Placebo; Matched placebo tablets 400 mg 3 times daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAEs	Serious adverse event (SAE) coded by System Organ Class (SOC) and Preferred Term (PT), using the Medical Dictionary for Regulatory Activities (MedDRA).	Day 1 to 6 weeks
TEAE	Proportion of patients with Treatment Emergent Adverse Events (TEAE) leading to study drug discontinuation.	Day 1 to 6 weeks
Fecal RNA Virus Clearance	Time to fecal viral RNA clearance (stool sample) assessed by RT-qPCR in the niclosamide arm compared to the placebo arm.	Day 1 to 6 weeks
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Leukocytes and Platelets)	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.	Day 1 to Day 43
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Erythrocytes)	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	Day 1 to Day 43
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemocrit)	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)	Day 1 to Day 43
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Hemoglobin)	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)	Day 1 to Day 43
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Corpuscular Volume)	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)	Day 1 to Day 43
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically BUN, Glucose, Chloride, Potassium, and Sodium)	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.	Day 1 to Day 43
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Alkaline Phosphatase, AST, ALT, and LDH)	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.	Day 1 to Day 43
Safety Laboratory Tests Including CBC, BUN, Blood Sugar, Electrolytes (Specifically Bilirubin and Serum Creatinine)	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.	Day 1 to Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Severity Score	Proportion of patients with each clinical severity score as recommended by the World Health Organization (WHO) for COVID-19 studies by study visit;	Day 1 to 6 weeks
Time to Resolution of Diarrhea	Time from the first dose of study treatment to the last loose or watery stool in patients with loose or watery stool (Bristol Stool Scale Types 5-7).	Day 1 to 6 weeks

Collaborators and Investigators

• Sponsor: Entero Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2021
• Primary Completion (Actual): June 4, 2022
• Study Completion (Actual): September 10, 2023

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: April 21, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: September 16, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Covid; Covid19 Diarrhea; Covid19 GI Infection
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Niclosamide
• Other Study ID Numbers: AZ-NICL-COV-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No