Trial to Evaluate Nitazoxanide for Treatment of Mild COVID-19 in Subjects Not at High Risk of Severe Illness

Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild COVID-19 in Subjects Not at High Risk of Severe Illness

The purpose of this study is to determine whether nitazoxanide (NTZ) is safe and effective for treatment of mild COVID-19 illness. Adults and adolescent participants will be followed for approximately 28 days.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Nitazoxanide; Dietary supplement: Vitamin Super-B Complex; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female at least 12 years of age
• Positive test for SARS-CoV-2 by RT-PCR or validated rapid antigen test within 72 hours prior to enrollment in the trial (positive sample must be collected within 72 hours prior to enrollment).

• Presence of clinical signs and/or symptoms consistent with worsening or stable mild COVID-19 (one of the following is required):

  1. Presence of at least two respiratory symptom domains (head, throat, nose, chest, cough) with a score of ≥2 as determined by Screening FLU-PRO AND
  2. Patient reported assessment that symptoms are present, the symptoms are not consistent with the subject's usual health, the symptoms interfere with daily activities, and the symptoms have worsened or remained the same relative to the previous day, as confirmed by responses to questions in the Screening FLU-PRO.
• Onset of symptoms no more than 72 hours before enrollment in the trial. Onset of symptoms is defined as the earlier of the first time at which the subject experienced subjective fever or any respiratory symptom (headache/head congestion, throat symptoms, nasal symptoms, chest symptoms, cough).
• Willing and able to provide written informed consent (including assent by legal guardian if under 18 years of age) and comply with the requirements of the protocol, including completion of the subject diary and all protocol procedures.

Exclusion Criteria:

• Persons with any clinical sign or symptoms suggestive of moderate or severe systemic illness with COVID-19, including the following:

  1. shortness of breath at rest,
  2. resting pulse ≥90 beats per minute,
  3. resting respiratory rate ≥20 breaths per minute, or
  4. oxygen saturation ≤ 93% on room air at sea level.

• Persons who have not been fully vaccinated against SARS-CoV-2 and are at high risk of progressing to severe COVID-19 illness due to having one of the following underlying conditions and/or sociodemographic risk factors:

  1. Age ≥ 55 years (with or without comorbidities),
  2. Body mass index (BMI) ≥30 kg/m² if ≥ 18 years of age or BMI ≥85th percentile for age and gender based on CDC growth charts,
  3. Chronic kidney disease,
  4. Diabetes,
  5. Cardiovascular disease (including congenital heart disease) or hypertension,
  6. Chronic lung disease (e.g., chronic obstructive pulmonary disease, moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension),
  7. Sickle cell disease,
  8. Neurodevelopmental disorders or other conditions that confer medical complexity.
• Subjects with immunosuppressive disease or receiving immunosuppressive treatment regardless of SARS-CoV-2 vaccination status.
• Subjects with active respiratory allergies or subjects expected to require anti-allergy medications during the study period for respiratory allergies.
• Females of childbearing potential who are either pregnant or sexually active without the use of birth control.
• Subjects residing in the same household with another subject participating in the study.
• Treatment with any investigational drug or vaccine therapy within 30 days prior to screening and willing to avoid them during the course of the study.
• Subjects who have received within the past 90 days or are expected to receive during the study period monoclonal antibody treatment or convalescent COVID-19 plasma for COVID-19.
• Receipt of any dose of NTZ within seven days prior to screening.
• Known sensitivity to NTZ or any of the excipients comprising the study medication.
• Subjects unable to swallow oral tablets or capsules.
• Subjects with known severe heart, lung, neurological or other systemic disease that the Investigator believes could preclude safe participation.
• Subjects likely or expected to require hospitalization unrelated to COVID-19 during the study period.
• Subjects taking medications considered to be major CYP2C8 substrates.
• Subjects who, in the judgment of the Investigator, will be unlikely to comply with the requirements of this protocol including completion of the subject diary.

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
Placebo Comparator: Placebo; Placebo tablets	Dietary supplement: Vitamin Super-B Complex; Vitamin Super-B Complex administered orally with food twice daily for 5 days to maintain the blind; Drug: Placebo; Two matching placebo tablets administered orally twice daily for 5 days
Active Comparator: Nitazoxanide; Nitazoxanide 300 mg extended release tablets	Drug: Nitazoxanide; Two NTZ 300 mg extended release tablets administered orally with food twice daily for 5 days; Other Names: NTZ; NT-300; Dietary supplement: Vitamin Super-B Complex; Vitamin Super-B Complex administered orally with food twice daily for 5 days to maintain the blind

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to sustained COVID-19 Recovery	Day 1 through Day 21

Other Outcome Measures

Outcome Measure	Time Frame
Change in cytokine levels	Day 1 through Day 4
Time to return to usual health	Day 1 through Day 21
Proportion of participants progressing to severe COVID-19 illness or death by any cause	Day 1 through Day 28

Collaborators and Investigators

• Sponsor: Romark Laboratories L.C.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: December 10, 2021
• First Submitted That Met QC Criteria: December 10, 2021
• First Posted (Actual): December 14, 2021

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2
• 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; Nitazoxanide
• Other Study ID Numbers: RM08-3011

Drug and device information, study documents

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