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

Phase 2

Completed

• Conditions: COVID-19
• Interventions: Drug: Niclosamide; Drug: Placebo

• Registration Number: NCT04603924
• Lead Sponsor: NeuroBo Pharmaceuticals Inc.

Brief Summary

Study of ANA001 in Moderate and Severe COVID-19 Patients

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 Timeline

• Study Start: 2020-10-07
• Study First Submitted: 2020-10-20
• Study First Submitted QC: 2020-10-23
• Study First Posted: 2020-10-27
• Primary Completion: 2022-02-16
• Study Completion: 2022-02-16
• Results First Submitted: 2024-08-06
• Status Verified: 2025-01
• Results First Submitted QC: 2025-04-29
• Last Update Submitted: 2025-04-29
• Results First Posted: 2025-05-15
• Last Update Posted: 2025-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ANA001	Niclosamide	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.
Matching Placebo	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.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Experiencing TEAEs	Randomization to Day 60	Incidence of Treatment Emergent Adverse Events (TEAEs)
Number of Subjects Experiencing TESAEs	Randomization to Day 60	Incidence of Treatment Emergent Serious Adverse Events (TESAEs)

Secondary Outcome Measures

Name	Time	Method
Median Time to Hospital Discharge	Randomization to Day 60	Median time until patient is discharged from hospital. Discharge is defined as a score of 1 or 2 in the WHO Ordinal Scale for Clinical Improvement. This is a 9 point ordinal scale with 0 indicating "No clinical or virological evidence of infection" and 8 indicating "Death".
Median Time to 2-point Improvement WHO Clinical Improvement Scale	Randomization to Day 60	Median Time to 2-point Improvement in WHO Ordinal Scale for Clinical Improvement. This is a 9 point ordinal scale with 0 indicating "No clinical or virological evidence of infection" and 8 indicating "Death"
Median Time to Resolution of COVID-19 Symptoms	Randomization to Day 60	Median time (in days) to resolution of subjective symptoms assessed by the Investigator to be potentially due to COVID-19 including: fever, cough (productive or non-productive), sore throat, malaise, headache, muscle pain, gastrointestinal symptoms (i.e., nausea, vomiting, or diarrhea), shortness of breath (with or without exertion), and respiratory distress
Median Time to Time-to-Viral Load Undetectable	Randomization to Day 60	Median number of days to viral load undetectable by nasopharyngeal (NP) swab
AUC 0-t (h*ng/mL)	Pre- dose (within 30mins prior to each dose) and 1, 4 and 8 hours after each dose.	Area under the drug concentration (h\*ng/mL) (AUC) vs time curve on Days 1 and 2
Cmax (ng/mL)	Pre- dose (within 30mins prior to each dose) and 1, 4 and 8 hours after each dose.	Maximum post dose plasma drug concentration on \[Cmax (ng/mL)\] Days 1 and 2
Tmax (h)	Pre- dose (within 30mins prior to each dose) and 1, 4 and 8 hours after each dose.	Time to maximum post dose plasma drug concentration on \[Tmax (h)\] Days 1 and 2

Trial Locations

Locations (8)

Baptist Health Research Institute; 🇺🇸 Jacksonville, Florida, United States

University of California, Irvine; 🇺🇸 Irvine, California, United States

AdventHealth Tampa; 🇺🇸 Tampa, Florida, United States

Helen Keller Hospital; 🇺🇸 Sheffield, Alabama, United States

University of Missouri Health Care; 🇺🇸 Columbia, Missouri, United States

Memorial Hermann Memorial City Medical Center; 🇺🇸 Houston, Texas, United States

Caroline Institute for Clinical Research; 🇺🇸 Fayetteville, North Carolina, United States

Providence Regional Medical Center Everett; 🇺🇸 Everett, Washington, United States