Study of Niclosamide in Moderate and Severe Hospitalized Coronavirus-19 (COVID-19) Patients

A Phase 2/3 Randomized and Placebo-Controlled Study of ANA001 in Moderate and Severe COVID-19 Patients

Study of ANA001 in Moderate and Severe COVID-19 Patients

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Niclosamide; Drug: Placebo

Detailed Description

This is a 2 part, Phase 2/3 multi-center, double blinded, placebo-controlled study to assess the safety, tolerability, and efficacy of oral niclosamide (ANA001) in moderate and severe hospitalized COVID-19 patients compared to placebo.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Andrew Bartynski; Phone Number: 1 650-263-1270; Email: andrew@neurobopharma.com

Study Locations

• United States
  • Alabama
    • Sheffield, Alabama, United States, 35660
      • Helen Keller Hospital
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Health Research Institute
    • Tampa, Florida, United States, 33613
      • AdventHealth Tampa
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Health Care
  • North Carolina
    • Fayetteville, North Carolina, United States, 28303
      • Caroline Institute for Clinical Research
  • Texas
    • Houston, Texas, United States, 77024
      • Memorial Hermann Memorial City Medical Center
  • Washington
    • Everett, Washington, United States, 92801
      • Providence Regional Medical Center Everett

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Provide written informed consent prior to performing study procedures
2. Hospitalized.
3. Male or female ≥18 years of age
4. Positive for severe acute respiratory syndrome coronavirus 2
5. Presence of symptoms of lower respiratory tract infection (LRTI) including at least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, or more significant lower respiratory tract symptoms, including shortness of breath
6. At least 1 of the following: respiratory rate (RR) ≥20 breaths per minute, room air oxygen saturation (SpO2) <98%, requirement for supplemental oxygen, heart rate (HR) ≥90 beats per minute, or temperature >38.3°C
7. Women of childbearing potential must agree to abstinent or use at least 1 form of contraception not including hormonal contraception from the day of screening through Day 30

Key Exclusion Criteria:

1. Hospitalized but no longer requires ongoing inpatient care (i.e., discharge is anticipated in ≤24 hours)
2. Patient is not anticipated to survive >48 hours OR is under palliative care

3. Evidence of critical illness, defined by at least 1 of the following:

   • Respiratory failure requiring at least 1 of the following:

     1. Endotracheal intubation and mechanical ventilation, oxygen delivered by high flow nasal cannula
     2. Noninvasive positive pressure ventilation (NIPVV), OR
     3. Extracorporeal membrane oxygenation (ECMO) or clinical diagnosis of respiratory failure
   • Shock (defined by systolic blood pressure (BP) <90 mm Hg, or diastolic blood pressure (BP) <60 mm Hg or requiring vasopressors), OR
   • Multi-organ dysfunction/failure
4. Severe central nervous system (CNS) conditions
5. Chronic kidney disease requiring dialysis
6. Known allergy to the study drug or salicylate containing medications.
7. Suspected and/or confirmed pregnancy or breastfeeding
8. Current or planned participation in any other clinical trial of a treatment being developed under a US investigational new drug (IND) or emergency use authorization (EUA).
9. Patients receiving chemotherapeutic agents and/or immunomodulators (including monoclonal antibodies (Mabs) or plasma transfusions) for chronic disease conditions.

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: ANA001; Subjects in the ANA001 treatment arm will receive 1,000 mg (4 capsules; 250 mg each) by mouth twice per day for 7 consecutive days with a meal. If the participant requires mechanical ventilation over the course of the study, ANA001 may be administered via nasogastric (NG), percutaneous endoscopic gastrostomy (PEG) or orogastric (OG) tube and, if possible, should be administered with a scheduled nasogastric (NG) or orogastric (OG) feeding.	Drug: Niclosamide; Niclosamide is an antihelmintic with in-vitro antiviral activity; Other Names: ANA001
Placebo Comparator: Matching Placebo; Subjects in the comparator arm will receive matching placebo (hydroxypropylmethylcellulose (HPMC)) (4 capsules, by mouth twice a day) for the 7-day treatment duration.	Drug: Placebo; Matching hydroxypropylmethylcellulose HPMC capsules with no active ingredients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of ANA001 as measured by the incidence of treatment emergent adverse events (TEAE's) (Part 1 and Part 2)	Incidence of treatment emergent adverse events (TEAE's)	Randomization to Day 28
Efficacy as measured by median time to hospital discharge (Part 2)	Median time to hospital discharge	Randomization to Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy as measured by median time to hospital discharge (Part 1)	Median time to hospital discharge	Randomization to Day 60
Pharmacokinetics (PK) of ANA001 as measured by plasma concentrations (Part 1)	Plasma concentrations of ANA001	Day 1, 2, 3 or 4
Efficacy of ANA001 as measured by mean change from baseline in the National Early Warning Score (NEWS 2) (Part 2)	Mean change from baseline in National Early Warning Score (NEWS 2) score	Day 15
Efficacy of ANA001 as measured by mean number of days on rescue therapy (Part 2)	Mean number of days on rescue therapy	Within 15 days after enrollment

Collaborators and Investigators

• Sponsor: NeuroBo Pharmaceuticals Inc.
• Investigators: Study Director: Doug Rank, MD, NeuroBo Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2020
• Primary Completion (Actual): February 16, 2022
• Study Completion (Actual): February 16, 2022

Study Registration Dates

• First Submitted: October 20, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 27, 2020

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Infection; Immunomodulator; ARDS; anti-inflammatory; Acute Respiratory Distress Syndrome; Virus; Antiviral; Acute Respiratory Distress Syndrome (ARDS); Viral; bronchodilator; Niclosamide; Corona Virus Disease (COVID-19); Oral Niclosamide; Cytokine dysregulation; anthelmintic; antineoplastic; ANA001; Moderate COVID-19; Hospitalized COVID-19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Niclosamide
• Other Study ID Numbers: ANA001-001

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