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

• ClinicalTrials.gov Identifier: NCT04563208
• Recruitment Status: Recruiting
• First Posted: September 24, 2020
• Last Update Posted: September 16, 2021
• Sponsor: University of Witwatersrand, South Africa
• Collaborator: SynaVir
• Information provided by (Responsible Party): Professor Francois Venter, University of Witwatersrand, South Africa

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Covid19; SARS-CoV Infection	Drug: Placebo; Drug: DuACT	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: December 9, 2020
• Estimated Primary Completion Date: February 28, 2022
• Estimated Study Completion Date: February 28, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Rate of decline in viral load [ Time Frame: 10 days ]
   Rate of decline in viral load over the 10 days after randomization between participants treated with RBV and NTZ for COVID-19 and placebo

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Simiso Sokhela; 82 339 2322 ext +27; ssokhela@ezintsha.org

Locations

South Africa

Sunnyside Office Park; Recruiting

Johannesburg, Gauteng, South Africa

Contact: Bronwyn Bosch, MBBCh +27113585300 bbosch@ezintsha.org

Contact: Godspower Akpomiemie, MPH +2711358 5370 gakpomiemie@ezintsha.org

Principal Investigator: Simiso Sokhela, MBBCh

Sub-Investigator: Nomathemba Chandiwana, MBBCh

Sub-Investigator: Joana Woods, MBBCh

Sponsors and Collaborators

University of Witwatersrand, South Africa

SynaVir

Investigators

• Principal Investigator: Simiso Sokhela; Ezintsha

More Information

• Responsible Party: Professor Francois Venter, Divisional Director: Ezintsha, University of Witwatersrand, South Africa
• ClinicalTrials.gov Identifier: NCT04563208
• Other Study ID Numbers: DUACT-101
• First Posted: September 24, 2020
• Last Update Posted: September 16, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Professor Francois Venter, University of Witwatersrand, South Africa:

Ribavirin; Nitazoxanide; SARS-CoV-2

Additional relevant MeSH terms:

COVID-19; Severe Acute Respiratory Syndrome; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases