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

Study Overview
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Brief Summary
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Study of ANA001 in Moderate and Severe COVID-19 Patients

Detailed Description
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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.

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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Niclosamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Provide written informed consent prior to performing study procedures Hospitalized. Male or female ≥18 years of age Positive for severe acute respiratory syndrome coronavirus 2 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 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 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: Hospitalized but no longer requires ongoing inpatient care (i.e., discharge is anticipated in ≤24 hours) Patient is not anticipated to survive >48 hours OR is under palliative care Evidence of critical illness, defined by at least 1 of the following: Respiratory failure requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, oxygen delivered by high flow nasal cannula Noninvasive positive pressure ventilation (NIPVV), OR 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 Severe central nervous system (CNS) conditions Chronic kidney disease requiring dialysis Known allergy to the study drug or salicylate containing medications. Suspected and/or confirmed pregnancy or breastfeeding 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). Patients receiving chemotherapeutic agents and/or immunomodulators (including monoclonal antibodies (Mabs) or plasma transfusions) for chronic disease conditions.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANA001<br>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<br>* Niclosamide is an antihelmintic with in-vitro antiviral activity<br>* Other names: ANA001;|
| Placebo Comparator: Matching Placebo<br>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<br>* Matching hydroxypropylmethylcellulose HPMC capsules with no active ingredients<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Virus, antineoplastic, Moderate COVID-19, ARDS, Acute Respiratory Distress Syndrome, Hospitalized COVID-19, Corona Virus Disease (COVID-19), Niclosamide, Antiviral, Immunomodulator, Oral Niclosamide, Infection, Acute Respiratory Distress Syndrome (ARDS), Cytokine dysregulation, Viral, anthelmintic, anti-inflammatory, bronchodilator, ANA001