Study of Oral Administration of Ribavirin and Nitazoxamide Versus Placebo in COVID-19 (DuACT)

A Randomized, Double-Blind, Study Comparing the Efficacy, Safety, and Tolerability of Oral Administration of Ribavirin (RBV) and Nitazoxamide (NTZ)Versus Placebo in SARS-CoV-2 Virus Infected Participants (DuACT)

This is a single center, randomized, double-blind, 2-arm, parallel-group study of DuACT in participants with clinical symptoms of COVID-19 that have begun within the past 72 hours prior to testing.

Study Overview

• Status: Completed
• Conditions: Covid19; SARS-CoV Infection
• Intervention / Treatment: Drug: Placebo; Drug: DuACT

Detailed Description

This is a single center, randomized, double-blind, 2-arm, parallel-group study of DuACT in participants with clinical symptoms of COVID-19 that have begun within the past 72 hours prior to testing. A confirmatory diagnosis of COVID-19 via nasopharyngeal swab, with a positive PCR result within 48 hours of testing.

Consented participants who complete screening and meet study eligibility criteria will be randomized in a 1:1 ratio to receive DuACT or Placebo for 5 days.

Study drugs will be administered BID for 5 days with a loading dose on Day 1. Following randomization, participants will complete a symptom questionnaire, record temperature and record oxygen saturation daily for 10 days and at day 28. A thermometer and pulse oximeter will be provided to each patient at the baseline visit (Day 1).

On study days 3, 6 and 10 participants will have a clinic or home visit by a home healthcare provider. At these visits, a mid-turbinate nasal swab will be obtained, confirmation of the patient's clinical symptoms questionnaire will be completed and any adverse events will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa
      • Sunnyside Office Park

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed a current EC approved informed consent form

2. Male or female participants between 18 and 75 years of age, inclusive diagnosis of SARS-CoV-2 infection, with all of the following, with onset of any within the 72 hours prior to testing:

   1. Presence of fever at time of screening of ≥ 38.0°C (≥ 100.0°F) and/or
   2. Presence of at least one constitutional symptom associated with Covid-19 (e.g. headache, myalgia, malaise, or fatigue, rash, diarrhea, loss or alteration of taste/smell) of any severity, and/or
   3. Presence of at least one respiratory symptom (e.g. cough, chest tightness or sore throat) and/or
3. Diagnosis of COVID-19 with a positive PCR in the past 48 hours

Exclusion Criteria:

1. Pregnant or lactating females

2. Critically ill with presence of one or more of the following signs:

   1. difficulty breathing or shortness of breath
   2. need for admission to a hospital or an intensive care unit,
   3. acute respiratory failure requiring intubation/mechanical ventilation,
   4. signs of shock including hypotension
   5. Oxygen saturation < 92 %
3. Any clinically significant screening laboratory results that are greater than 5 times the upper limit of normal.
4. Estimated GFR < 50 mL/min/1.73 m2 (calculated using either Modification of Diet in Renal Disease (MDRD) or Cockcroft Gualt
5. Known genetic hemoglobinopathy (e.g., thalassemia major or sickle cell anemia) or autoimmune hemolytic anemia
6. Hemoglobin less than 10 gm/dL or hematocrit < 30 %
7. Retinal eye disease
8. Known chronic kidney disease, stage - 5 or receiving dialysis
9. Inability to tolerate oral medications
10. Allergy or prior adverse reaction to either ribavirin or nitazoxanide
11. QTc interval > 450 mSEC for men and women
12. History of Torsade de Pointes VT or prior cardiac arrest or congenital long QT interval
13. Current treatment with histamine-2 receptor antagonists (H2 blockers) and/or Protein Pump Inhibitors and throughout the study.
14. Have been vaccinated against COVID-19
15. Have participated in a clinical study in the past 30 days
16. Any physical, mental, or social condition, drug/alcohol use, history of illness or laboratory abnormality that in the investigator's judgment might interfere with study procedures or the ability of the subject to adhere to and complete the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm A: Placebo; Placebo administered	Drug: Placebo; Placebo administered on Days 1-5
Active Comparator: Arm B: Ribavirin/Nitazoxanide (RBV/NTZ); Ribavirin/Nitazoxanide (RBV/NTZ) administered	Drug: DuACT; Day1: RBV 600 mg BID and NTZ 500 mg BID Days 2-5: RBV 400 mg BID and NTZ 500 mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of decline in viral load	Rate of decline in viral load over the 10 days after randomization between participants treated with RBV and NTZ for COVID-19 and placebo	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to resolution of viral load	Time to resolution of viral load, defined by reduction of virus below LLOQ and maintaining it for 2 days.	28 days
Comparison of proportion of subjects who are asymptomatic and symptomatic	Comparison of proportion of subjects who are asymptomatic and symptomatic at day 10	10 days
Rate of decline in viral load	To assess the rate of decline in viral load over days 3 and 6 after randomization	Days 3 and 6
Change in modified NEWS-2	Assess change in modified National Early Warning System-2 items on a scale of 0 to 20. HIgher scores meaning greater clinical risk.	28 days
Proportion of subjects with treatment emergent adverse events	Proportion of subjects with treatment emergent adverse events leading to study drug discontinuation	28 days

Collaborators and Investigators

• Sponsor: University of Witwatersrand, South Africa
• Collaborators: SynaVir
• Investigators: Principal Investigator: Simiso Sokhela, Ezintsha

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2020
• Primary Completion (Actual): February 28, 2022
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 13, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Ribavirin; Nitazoxanide
• 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; Severe Acute Respiratory Syndrome; COVID-19
• Other Study ID Numbers: DUACT-101

Drug and device information, study documents

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