Niclosamide in COVID-19

Study Overview
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Brief Summary
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This is a two-part, Phase 2, multicentre, randomized, double blind, 2-arm placebo-controlled study in adults with moderate COVID-19 with gastrointestinal signs and symptoms

Official Title
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A Phase 2 Randomized Double Blind, Placebo-controlled Study on the Safety and Efficacy of Niclosamide in Patients With COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Drug: Niclosamide Oral Tablet
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1 only: Patients hospitalized with a primary diagnosis of COVID-19 with or without pneumonia, who are expected to remain in hospital at least seven days after the randomization and who accept continuing to be assessed for the study procedures (home or outpatient unit) up to 6 weeks in case of discharge. Part 2 only: Patients with a primary diagnosis of COVID-19 with or without pneumonia who are not planned to be hospitalized. Patients who prior to developing COVID-19 usually have normal bowel habits defined as at least solid-formed 3 stools per week and no more than 3 solid-formed stools per day. SARS-CoV-2 RNA presence in rectal swab (or stool test) ≤2 days before randomization by local or central lab. Diarrhea defined as at least 3 watery stools in the last 24 hours prior to enrolment Exclusion Criteria: At the time of randomization patients requiring ICU admission or patients with severe respiratory insufficiency requiring mechanical ventilation or with rapid worsening of respiratory function leading to expectation for mechanical ventilation or ICU admission. Evidence of rapid clinical deterioration or existence of any life-threatening co-morbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion.

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: Niclosamide<br> | Drug: Niclosamide Oral Tablet<br>* Niclosamide tablets 400 mg 3 times daily for 14 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo tablets 3 times daily for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | All-cause mortality | From Day 1 to 6 weeks | 
| TEAE | Proportion of patients with Treatment Emergent Adverse Events (TEAE) leading to study drug discontinuation | From Day 1 to 6 weeks | 
| SAEs | Serious adverse event (SAE) coded by System Organ Class (SOC) and Preferred Term (PT), using the Medical Dictionary for Regulatory Activities (MedDRA) | From Day 1 to end of study | 
| Safety laboratory | Change in safety laboratory tests 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 | From Day 1 to 6 weeks | 
| Blood pressure | Change in sitting systolic and diastolic blood pressure from baseline to 6 weeks summarized descriptively by visit and presented as shift tables | From Day 1 to 6 weeks | 
| fecal RNA virus clearance | time to fecal RNA virus clearance (rectal swab or stool sample) assessed by RT-qPCR in the niclosamide group, compared to the placebo group (Part 2 only) | From Day 1 to 6 weeks | 
| Body temperature | Change in body temperature from baseline to 6 weeks summarized descriptively by visit and presented as shift tables | From Day 1 to 6 weeks | 
| Heart rate | Change in heart rate from baseline to 6 weeks summarized descriptively by visit and presented as shift tables | From Day 1 to 6 weeks | 
| SaO2 | Change in SaO2 from baseline to 6 weeks summarized descriptively by visit and presented as shift tables | From Day 1 to 6 weeks | 
| ECG | Change in ECG parameters including: 1. PR interval 2. RR interval 3. QRS interval 4 QT interval 5. HR interval 6. QtcF interval. All intervals summarized descriptively by visit from baseline to 6 weeks | From Day 1 to 6 weeks |