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

NCT04532931 | Completed Phase 2 Results DMC

• 1 other identifier: SP-PA-COV-202
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Keywords

COVID-19; Pyramax; Pyronaridine; Artesunate; Chloroquine; Zinc; Amodiaquine; Favipiravir; Nitazoxanide; Sofosbuvir; Daclatasvir

Outcome Measures

Primary Outcomes (1)

• Incidence of SARS-CoV-2 Clearance

  Day 7

Secondary Outcomes (14)

• Incidence of SARS-CoV-2 Clearance

  Day 3, 10, 14, 21, 28

• Time to Clearance of Nasal SARS-CoV-2

  Day 0, 3, 7, 10, 14, 21, 28

• Estimated Viral Load of SARS-CoV-2 Detected by Quantitative RT-PCR

  Day 14

• Poisson Regression for Proportion of Days With Fever After Randomization

  Day 28

• Percentage of Days With Respiratory Symptoms After Randomization

  from randomization to end of study (until day 28)

Study Arms (5)

Paracetamol (SOC)

PLACEBO COMPARATOR

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

Drug: Paracetamol

Artesunate-amodiaquine (ASAQ)

EXPERIMENTAL

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

Drug: Artesunate-amodiaquine

Pyronaridine-artesunate (PA)

EXPERIMENTAL

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

Drug: Pyronaridine-artesunate

Favipiravir plus nitazoxanide (FPV-NTZ)

EXPERIMENTAL

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

Drug: Favipiravir plus Nitazoxanide

SOC plus Sofosbuvir/daclatasvir

EXPERIMENTAL

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

Drug: Sofosbuvir/daclatasvir

Interventions

Paracetamol DRUG

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

Also known as: Control treatment (SoC)

Paracetamol (SOC)

Artesunate-amodiaquine DRUG

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

Also known as: ASAQ

Artesunate-amodiaquine (ASAQ)

Pyronaridine-artesunate 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

Also known as: PA

Pyronaridine-artesunate (PA)

Favipiravir plus Nitazoxanide 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

Also known as: FPV-NTZ

Favipiravir plus nitazoxanide (FPV-NTZ)

Sofosbuvir/daclatasvir DRUG

SOC plus sofosbuvir/daclatasvir (SOF/DCV) 1 tablet (400 mg/60 mg sofosbuvir/daclatasvir) daily for 7 days

Also known as: SOF/DCV

SOC plus Sofosbuvir/daclatasvir

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age from 18 to 65 years of age, inclusive, at the time of signing the informed consent.
• Willing and able to provide informed consent.
• 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.
• 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.
• 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.
• Body weight ≥45 kg.
• Access to reliable video conference, telephone, direct/text messaging, or other device permitting real-time, reliable information transfer.

You may not qualify if:

• Pregnant or lactating women.
• Known hypersensitivity or specific contraindications to the use of any of the active drugs in the treatment arms, or similar compounds.
• Signs of respiratory distress prior to randomization, including:
• respiratory rate \>24 breaths/min
• SpO2 \<95% in room air.
• Resting pulse rate ≥120 beats/min.
• High likelihood of hospitalization in the opinion of the attending clinician.
• QTcF \>470 msec for females, or \>450 msec for males, at screening.
• Serum potassium \<3.5 mmol/L at screening.
• 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 \[class 2 or higher using the New York Heart Association functional classification\]).
• Known chronic kidney disease (Stage IV or receiving dialysis).
• Known cirrhosis (Child-Pugh Class B or greater).
• Known macular degeneration, or other known retinal diseases, or 4-aminoquinolone-induced visual impairment.
• Currently receiving, or recently received (within 60 days prior to randomization) treatment with any of the drugs in the treatment arms.
• Currently receiving, or recently received (within 30 days prior to randomization) treatment with any antimalarial drugs.

Sponsors & Collaborators

• Shin Poong Pharmaceutical Co. Ltd.: lead
• Medicines for Malaria Venture: collaborator

Study Sites (1)

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

Johannesburg, South Africa

Location

MeSH Terms

Conditions

COVID-19

Interventions

Acetaminophen; amodiaquine, artesunate drug combination; pyronaridine tetraphosphate, artesunate drug combination; favipiravir; nitazoxanide; Sofosbuvir; daclatasvir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Shin Poong Pharm. Co., Ltd.
• Organization: Shin Poong Pharm. Co., Ltd.

bwon@shinpoong.co.kr

82-2-2189-3478

Study Officials

• Francois Venter, PhD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: August 31, 2020
• Study Start: September 3, 2020
• Primary Completion: August 5, 2021
• Study Completion: August 23, 2021
• Last Updated: July 28, 2025
• Results First Posted: July 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)