Four Different Experimental Drug Regimens to Standard of Care for the Treatment of Symptomatic Outpatients With COVID-19

NCT ID: NCT04532931

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-03
• Study Completion Date: 2021-08-23

Brief Summary

This exploratory study is a randomized, single center, open label study of four different experimental treatment arms versus standard of care for the treatment of SARS-CoV-2 infection in symptomatic outpatients with mild disease at the time of enrollment.

Detailed Description

This phase 2, exploratory study will be an adaptive, randomized, open label, trial for treatment of individuals in an outpatient settings with mild SARS-CoV-2 infection. The primary outcome is focused on the evaluation of efficacy of the proposed experimental drugs in reducing upper respiratory viral shedding, defined as viral clearance (i.e., negative swab) on Day 7. Key secondary outcomes focus on other measures of viral shedding, safety evaluation, progression to LRTI (defined by resting blood oxygen saturation level [SpO2] <93% sustained for two readings two hours apart and presence of subjective dyspnoea or cough), disease severity, clinical resolution rate, and cumulative incidence of hospitalization or mortality at Day 28.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Paracetamol (SOC)

500 mg oral tablets. Two tablets taken at 6-hour intervals as needed, in all treatment arms (in addition to any investigative treatment)

Group Type: PLACEBO_COMPARATOR

Paracetamol

Intervention Type: DRUG

SOC - 2 tablets (1000 mg) to be taken 6-hourly as needed

Artesunate-amodiaquine (ASAQ)

Fixed dose combination tablets containing 100 mg artesunate and 270 mg amodiaquine. Participants received two tablets once daily for 3 days

Group Type: EXPERIMENTAL

Artesunate-amodiaquine

Intervention Type: DRUG

SOC plus artesunate-amodiaquine (ASAQ) - 2 tablets (200/540 mg artesunate/amodiaquine) daily for 3 days

Pyronaridine-artesunate (PA)

Fixed dose combination tablets containing 180 mg pyronaridine and 60 mg artesunate, given once daily for 3 days. Participants weighing 45 to \<65 kg received 3 tablets per dose, those ≥65 kg received 4 tablets per dose

Group Type: EXPERIMENTAL

Pyronaridine-artesunate

Intervention Type: DRUG

SOC plus pyronaridine-artesunate (PA) Weight 45 to \<65 kg: 3 tablets (540/180 mg pyronaridine/artesunate) daily for 3 days Weight ≥65 kg: 4 tablets (720/240 mg pyronaridine/artesunate) daily for 3 days

Favipiravir plus nitazoxanide (FPV-NTZ)

Free combination of favipiravir 200 mg and 400 mg tablets and nitazoxanide 500 mg tablets. Participants received favipiravir as a loading dose of 1600 mg twice daily for 1 day followed by 600 mg twice daily for 6 days, and nitazoxanide 1000 mg twice daily, with food, for 7 days

Group Type: EXPERIMENTAL

Favipiravir plus Nitazoxanide

Intervention Type: DRUG

SOC plus favipiravir plus nitazoxanide (FPV-NTZ) Favipiravir: 1600 mg 12-hourly for 1 day then 600 mg 12-hourly for 6 days Nitazoxanide: 2 tablets (1000 mg) 12-hourly for 7 days

SOC plus Sofosbuvir/daclatasvir

Fixed dose combination tablets containing 400 mg sofosbuvir and 60 mg daclatasvir. Participants received 1 tablet once daily for 7 days

Group Type: EXPERIMENTAL

Sofosbuvir/daclatasvir

Intervention Type: DRUG

SOC plus sofosbuvir/daclatasvir (SOF/DCV)

1 tablet (400 mg/60 mg sofosbuvir/daclatasvir) daily for 7 days

Interventions

Paracetamol

SOC - 2 tablets (1000 mg) to be taken 6-hourly as needed

Intervention Type: DRUG

Artesunate-amodiaquine

SOC plus artesunate-amodiaquine (ASAQ) - 2 tablets (200/540 mg artesunate/amodiaquine) daily for 3 days

Intervention Type: DRUG

Pyronaridine-artesunate

SOC plus pyronaridine-artesunate (PA) Weight 45 to \<65 kg: 3 tablets (540/180 mg pyronaridine/artesunate) daily for 3 days Weight ≥65 kg: 4 tablets (720/240 mg pyronaridine/artesunate) daily for 3 days

Intervention Type: DRUG

Favipiravir plus Nitazoxanide

SOC plus favipiravir plus nitazoxanide (FPV-NTZ) Favipiravir: 1600 mg 12-hourly for 1 day then 600 mg 12-hourly for 6 days Nitazoxanide: 2 tablets (1000 mg) 12-hourly for 7 days

Intervention Type: DRUG

Sofosbuvir/daclatasvir

SOC plus sofosbuvir/daclatasvir (SOF/DCV)

1 tablet (400 mg/60 mg sofosbuvir/daclatasvir) daily for 7 days

Intervention Type: DRUG

Other Intervention Names

Control treatment (SoC); ASAQ; PA; FPV-NTZ; SOF/DCV

Eligibility Criteria

Inclusion Criteria

1. Age from 18 to 65 years of age, inclusive, at the time of signing the informed consent.

2. Willing and able to provide informed consent.

3. Women of reproductive potential must be using a highly effective method of contraception for at least 28 days prior to enrolment and must be able and willing to continue its use throughout the duration of the study.

4. Men must agree to use condoms when engaging in heterosexual sex during the study and for the period up to 91 days after the last dose of study medication. Men who are not randomized to a treatment arm including favipiravir (or another arm identified as having teratogenic potential through semen) will no longer need to adhere to this after randomization.

5. Laboratory confirmed SARS-CoV-2 infection, and any of the following self-reported symptoms within 72 hours prior to randomization: fever or chills, cough, myalgia, sore throat, shortness of breath, or new onset of anosmia or ageusia.

6. Body weight ≥45 kg.

7. Access to reliable video conference, telephone, direct/text messaging, or other device permitting real-time, reliable information transfer.

Exclusion Criteria

1. Pregnant or lactating women.

2. Known hypersensitivity or specific contraindications to the use of any of the active drugs in the treatment arms, or similar compounds.

3. Signs of respiratory distress prior to randomization, including:

• respiratory rate >24 breaths/min
• SpO2 <95% in room air.

4. Resting pulse rate ≥120 beats/min.

5. High likelihood of hospitalization in the opinion of the attending clinician.

6. QTcF >470 msec for females, or >450 msec for males, at screening.

7. Serum potassium <3.5 mmol/L at screening.

8. History of clinically significant cardiovascular disease (including arrhythmias, QT-interval prolongation, torsades de pointes (TdP), history of coronary artery disease with graft or stent procedures/surgery, cardiac failure [class 2 or higher using the New York Heart Association functional classification]).

9. Known chronic kidney disease (Stage IV or receiving dialysis).

10. Known cirrhosis (Child-Pugh Class B or greater).

11. Known macular degeneration, or other known retinal diseases, or 4-aminoquinolone-induced visual impairment.

12. Currently receiving, or recently received (within 60 days prior to randomization) treatment with any of the drugs in the treatment arms.

13. Currently receiving, or recently received (within 30 days prior to randomization) treatment with any antimalarial drugs.

14. Currently on treatment with drugs with known arrhythmogenic potential, or those known to induce significant QT-interval prolongation or TdP, as detailed in Appendix 6.

15. Currently on treatment for tuberculosis (or on treatment with rifampicin for any other indication), or on treatment with a protease inhibitor-based antiretroviral regimen, or efavirenz, or carbamazepine.

16. Inability/unlikely to be in the study area for the duration of the 28 day follow-up period.

17. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the safety of the volunteer or the objectives of the study. The Investigator should make this determination in consideration of the volunteer's medical history.

18. Personnel (e.g. investigator, sub-investigator, research assistant, pharmacist, study coordinator or anyone mentioned in the delegation log) directly involved in the conduct of the study.

19. Participant is judged by the Investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medicines for Malaria Venture

OTHER

Sponsor Role: collaborator

Shin Poong Pharmaceutical Co. Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francois Venter, PhD

Role: PRINCIPAL_INVESTIGATOR

Ezintsha, Wits Reproductive Health & HIV Institute University of the Witwatersrand

Locations

Ezintsha, Wits Reproductive Health & HIV Institute University of the Witwatersrand

Johannesburg, , South Africa

Countries

South Africa

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SP-PA-COV-202

Identifier Type: -

Identifier Source: org_study_id