COVID-19Phase 2NCT04532931
Four Different Experimental Drug Regimens to Standard of Care for the Treatment of Symptomatic Outpatients With COVID-19
A Phase 2 study testing Paracetamol, Artesunate-amodiaquine and Pyronaridine-artesunate in people with COVID-19, run by Shin Poong Pharmaceutical Co. Ltd. at 1 site in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Paracetamol, Artesunate-amodiaquine and Pyronaridine-artesunate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 192 participants
- Where
- 1 siteSouth Africa
- Study dates
- 3 Sep 2020to 23 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- 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.
- 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.
- Inability/unlikely to be in the study area for the duration of the 28 day follow-up period.
- 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.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Ezintsha, Wits Reproductive Health & HIV Institute University of the Witwatersrand
Johannesburg
About this study
Official title: Phase 2, Exploratory, Single Center, Randomized, Open Label, Adaptive Clinical Trial to Compare Safety and Efficacy of Four Different Experimental Drug Regimens to Standard of Care for the Treatment of Symptomatic Outpatients With COVID-19
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.
Read the 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
- Being tested
- Paracetamol, Artesunate-amodiaquine, Pyronaridine-artesunate, Favipiravir plus Nitazoxanide, Sofosbuvir/daclatasvir
- Keywords
- COVID-19, Pyramax, Pyronaridine, Artesunate, Chloroquine, Zinc, Amodiaquine, Favipiravir, Nitazoxanide, Sofosbuvir, Daclatasvir
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ParacetamolDrug
Also called Control treatment (SoC)
SOC - 2 tablets (1000 mg) to be taken 6-hourly as needed
Artesunate-amodiaquineDrug
Also called ASAQ
SOC plus artesunate-amodiaquine (ASAQ) - 2 tablets (200/540 mg artesunate/amodiaquine) daily for 3 days
Pyronaridine-artesunateDrug
Also called PA
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 NitazoxanideDrug
Also called FPV-NTZ
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
Sofosbuvir/daclatasvirDrug
Also called SOF/DCV
SOC plus sofosbuvir/daclatasvir (SOF/DCV)
1 tablet (400 mg/60 mg sofosbuvir/daclatasvir) daily for 7 days
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Sofosbuvir/daclatasvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of SARS-CoV-2 Clearance
Measured: Day 7
Secondary outcomes (14)
Incidence of SARS-CoV-2 Clearance
Measured: Day 3, 10, 14, 21, 28
Time to Clearance of Nasal SARS-CoV-2
Measured: Day 0, 3, 7, 10, 14, 21, 28
Estimated Viral Load of SARS-CoV-2 Detected by Quantitative RT-PCR
baseline and day14, Day 14 value minus baseline value
Measured: Day 14
Poisson Regression for Proportion of Days With Fever After Randomization
Measured: Day 28
Percentage of Days With Respiratory Symptoms After Randomization
"Percentage of total study days in which participants experienced respiratory symptoms until day 28. Percentage calculated as (No. of days with respiratory symptoms) ÷ (No. of days observation) x 100"
Measured: from randomization to end of study (until day 28)
FLU-PRO Plus Questionnaire Scores and FLU-PRO Plus Global Additional Daily Diary Items Over the First 14 Days
baseline and day 14, Day 14 value minus baseline value The FLU-PRO(inFLUenza Patient-Reported Outcome) Plus questionnaire was completed daily during the first 14 days, at Day 21 and at Day 28.
From these items six domain scores for the body areas Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, and Body/Systemic could be computed ranging from 0 (symptom free) to 4 (very severe symptoms).
Total Score Range for FLU-PRO Plus
- Score range per item: 0 (no symptoms) to 4 (very severe symptoms). A higher score indicates worse symptoms.
- Total score calculation: The mean (average) of all item scores is used. (Minimum score: 0, Maximum score: 4)
Measured: 14 days
Serious Adverse Events
Measured: Day 28
Adverse Events
Measured: Day 28
Related Adverse Events
Measured: Day 28
LRTI
Measured: Day 28
Maximum Score on WHO Ordinal Scale for Clinical Improvement During Study Participation
Measured: Day 28
Cumulative Incidence of Hospitalization
Measured: Day 28
Days of Hospitalization
Total number of hospitalization days for hospitalized participants in each group
Measured: Day 28
Cumulative Incidence of Mortality, Measured at Day 28 or Later if Participant is Hospitalized at the Time of Day 28
Measured: at Day 28 or later if participant is hospitalized at the time of Day 28 for up to 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2020
- Study start3 Sep 2020
- Primary completion5 Aug 2021
- Study completion23 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shin Poong Pharmaceutical Co. Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medicines for Malaria Venture
- Responsible party
- Sponsor
- Investigators
- Francois Venter, PhD, Principal investigator, Ezintsha, Wits Reproductive Health & HIV Institute University of the Witwatersrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04532931
- Sponsor's protocol ID
- SP-PA-COV-202
- Status last verified
- Feb 2025
- First submitted
- 26 Aug 2020
- Last updated
- 28 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2, Exploratory, Single Center, Randomized, Open Label, Adaptive Clinical Trial to Compare Safety and Efficacy of Four Different Experimental Drug Regimens to Standard of Care for the Treatment of Symptomatic Outpatients With COVID-19
- ClinicalTrials.gov ID
- NCT04532931
- Acronym / sponsor ID
- SP-PA-COV-202
- Conditions
- COVID-19
- Keywords
- COVID-19, Pyramax, Pyronaridine, Artesunate, Chloroquine, Zinc, Amodiaquine, Favipiravir
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Shin Poong Pharmaceutical Co. Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Medicines for Malaria Venture
- Study start
- 3 Sep 2020 (actual)
- Primary completion
- 5 Aug 2021 (actual)
- Study completion
- 23 Aug 2021 (actual)
- First posted
- 31 Aug 2020 (actual)
- Results
- Posted 28 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Paracetamol (SOC) | Placebo comparator | Drug: Paracetamol500 mg oral tablets. Two tablets taken at 6-hour intervals as needed, in all treatment arms (in addition to any investigative treatment) |
| Artesunate-amodiaquine (ASAQ) | Experimental | Drug: Artesunate-amodiaquineFixed dose combination tablets containing 100 mg artesunate and 270 mg amodiaquine. Participants received two tablets once daily for 3 days |
| Pyronaridine-artesunate (PA) | Experimental | Drug: Pyronaridine-artesunateFixed 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 |
| Favipiravir plus nitazoxanide (FPV-NTZ) | Experimental | Drug: Favipiravir plus NitazoxanideFree 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 |
| SOC plus Sofosbuvir/daclatasvir | Experimental | Drug: Sofosbuvir/daclatasvirFixed dose combination tablets containing 400 mg sofosbuvir and 60 mg daclatasvir. Participants received 1 tablet once daily for 7 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (21 listed)
- 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:
- Resting pulse rate ≥120 beats/min.
- High likelihood of hospitalization in the opinion of the attending clinician.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ParacetamolAlso: Control treatment (SoC)SOC - 2 tablets (1000 mg) to be taken 6-hourly as needed | Drug | Paracetamol (SOC) |
| Artesunate-amodiaquineAlso: ASAQSOC plus artesunate-amodiaquine (ASAQ) - 2 tablets (200/540 mg artesunate/amodiaquine) daily for 3 days | Drug | Artesunate-amodiaquine (ASAQ) |
| Pyronaridine-artesunateAlso: PASOC 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 | Drug | Pyronaridine-artesunate (PA) |
| Favipiravir plus NitazoxanideAlso: FPV-NTZSOC 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 | Drug | Favipiravir plus nitazoxanide (FPV-NTZ) |
| Sofosbuvir/daclatasvirAlso: SOF/DCVSOC plus sofosbuvir/daclatasvir (SOF/DCV) 1 tablet (400 mg/60 mg sofosbuvir/daclatasvir) daily for 7 days | Drug | SOC plus Sofosbuvir/daclatasvir |
Primary outcome
Incidence of SARS-CoV-2 Clearance
Time frame: Day 7
14 secondary outcomes
Incidence of SARS-CoV-2 Clearance
Time frame: Day 3, 10, 14, 21, 28
Time to Clearance of Nasal SARS-CoV-2
Time frame: Day 0, 3, 7, 10, 14, 21, 28
Estimated Viral Load of SARS-CoV-2 Detected by Quantitative RT-PCR
Time frame: Day 14
Poisson Regression for Proportion of Days With Fever After Randomization
Time frame: Day 28
Percentage of Days With Respiratory Symptoms After Randomization
Time frame: from randomization to end of study (until day 28)
FLU-PRO Plus Questionnaire Scores and FLU-PRO Plus Global Additional Daily Diary Items Over the First 14 Days
Time frame: 14 days
Serious Adverse Events
Time frame: Day 28
Adverse Events
Time frame: Day 28
Related Adverse Events
Time frame: Day 28
LRTI
Time frame: Day 28
Maximum Score on WHO Ordinal Scale for Clinical Improvement During Study Participation
Time frame: Day 28
Cumulative Incidence of Hospitalization
Time frame: Day 28
Days of Hospitalization
Time frame: Day 28
Cumulative Incidence of Mortality, Measured at Day 28 or Later if Participant is Hospitalized at the Time of Day 28
Time frame: at Day 28 or later if participant is hospitalized at the time of Day 28 for up to 2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francois Venter, PhD principal investigator
Ezintsha, Wits Reproductive Health & HIV Institute University of the Witwatersrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paracetamol, Artesunate-amodiaquine and Pyronaridine-artesunate in people with COVID-19, run by Shin Poong Pharmaceutical Co. Ltd. at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of SARS-CoV-2 Clearance (time frame: Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2025.