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COVID-19 Treatment in South Africa

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ClinicalTrials.gov Identifier: NCT04532931
Recruitment Status : Completed
First Posted : August 31, 2020
Last Update Posted : September 20, 2021
Sponsor:
Collaborator:
Medicines for Malaria Venture
Information provided by (Responsible Party):
Shin Poong Pharmaceutical Co. Ltd.

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.

Condition or disease Intervention/treatment Phase
COVID-19 Other: Standard of care (Paracetamol) Drug: Artesunate-amodiaquine Drug: Pyronaridine-artesunate Drug: Favipiravir plus Nitazoxanide Drug: Sofosbuvir/daclatasvir Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 192 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 3, 2020
Actual Primary Completion Date : August 5, 2021
Actual Study Completion Date : August 23, 2021

Arm Intervention/treatment
Placebo Comparator: Arm A
Paracetamol (SOC)
Other: Standard of care (Paracetamol)
SOC - 2 tablets (1000 mg) to be taken 6-hourly as needed

Experimental: Arm B
SOC plus Artesunate-Amodiaquine
Drug: Artesunate-amodiaquine
SOC plus artesunate-amodiaquine (ASAQ) - 2 tablets (200/540 mg artesunate/amodiaquine) daily for 3 days

Experimental: Arm C
SOC plus Pyronaridine-Artesunate
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

Experimental: Arm D
SOC plus Favipiravir plus Nitazoxanide
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

Experimental: Arm E
SOC plus Sofosbuvir/daclatasvir
Drug: Sofosbuvir/daclatasvir

SOC plus sofosbuvir/daclatasvir (SOF/DCV)

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





Primary Outcome Measures :
  1. Incidence of SARS-CoV-2 clearance [ Time Frame: Day 7 ]
    Defined as the proportion of participants with a negative nasal swab


Secondary Outcome Measures :
  1. Incidence of SARS-CoV-2 clearance [ Time Frame: Day 10, 14, 21, 28 ]
    Defined as the proportion of participants with a negative nasal swab

  2. Time to clearance of nasal SARS-CoV-2 [ Time Frame: Day 0, 3, 7, 10, 14, 21, 28 ]
    Defined as a negative swab

  3. Median quantity of SARS-CoV-2 [ Time Frame: Day 14 ]
    Detected from mid-nasal swabs by PCR

  4. Proportion of days with fever after randomization [ Time Frame: Day 28 ]
    Number of days with fever

  5. Proportion of days with respiratory symptoms after randomization [ Time Frame: Day 28 ]
    Number of days with respiratory symptoms

  6. FLU-PRO© Plus [ Time Frame: 14 days ]

    FLU-PRO© Plus questionnaire scores and FLU-PRO© Plus Global Additional Daily Diary Items

    *The Influenza Patient-Reported Outcome instrument (FLU-PRO© Plus)


  7. Serious adverse events [ Time Frame: Day 28 ]
    Serious adverse events

  8. Adverse events resulting in treatment discontinuation [ Time Frame: Day 28 ]
    Adverse events

  9. Adverse events considered related to the investigational products [ Time Frame: Day 28 ]
    Related adverse events

  10. LRTI [ Time Frame: Day 28 ]
    Resting SpO2<93% sustained for 2 readings 2 hours apart AND presence of subjective dyspnea or cough in participants with access to SpO2

  11. Maximum score on WHO Ordinal Scale for Clinical Improvement during study participation [ Time Frame: Day 28 ]
    score 0(Uninfected)~ score 8(Dead)

  12. Cumulative incidence of hospitalization [ Time Frame: Day 28 ]
    frequency of patients requiring time in hospital

  13. Days of hospitalization [ Time Frame: Day 28 ]
    length of hospital stay

  14. Cumulative incidence of mortality [ Time Frame: Day 28 or later if participant is hospitalized at the time of Day 28 ]
    incidence of death



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04532931


Locations
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South Africa
Ezintsha, Wits Reproductive Health & HIV Institute University of the Witwatersrand
Johannesburg, South Africa
Sponsors and Collaborators
Shin Poong Pharmaceutical Co. Ltd.
Medicines for Malaria Venture
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Responsible Party: Shin Poong Pharmaceutical Co. Ltd.
ClinicalTrials.gov Identifier: NCT04532931    
Other Study ID Numbers: SP-PA-COV-202
First Posted: August 31, 2020    Key Record Dates
Last Update Posted: September 20, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shin Poong Pharmaceutical Co. Ltd.:
COVID-19
Pyramax
Pyronaridine
Artesunate
Chloroquine
Zinc
Amodiaquine
Favipiravir
Nitazoxanide
Sofosbuvir
Daclatasvir
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Acetaminophen
Sofosbuvir
Artesunate
Favipiravir
Amodiaquine
Nitazoxanide
Pyronaridine
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Antiviral Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents