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COVID-19 Treatment in South Africa

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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.

Tracking Information
First Submitted Date  ICMJE August 26, 2020
First Posted Date  ICMJE August 31, 2020
Last Update Posted Date September 20, 2021
Actual Study Start Date  ICMJE September 3, 2020
Actual Primary Completion Date August 5, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2020)
Incidence of SARS-CoV-2 clearance [ Time Frame: Day 7 ]
Defined as the proportion of participants with a negative nasal swab
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2020)
  • Incidence of SARS-CoV-2 clearance [ Time Frame: Day 10, 14, 21, 28 ]
    Defined as the proportion of participants with a negative nasal swab
  • Time to clearance of nasal SARS-CoV-2 [ Time Frame: Day 0, 3, 7, 10, 14, 21, 28 ]
    Defined as a negative swab
  • Median quantity of SARS-CoV-2 [ Time Frame: Day 14 ]
    Detected from mid-nasal swabs by PCR
  • Proportion of days with fever after randomization [ Time Frame: Day 28 ]
    Number of days with fever
  • Proportion of days with respiratory symptoms after randomization [ Time Frame: Day 28 ]
    Number of days with respiratory symptoms
  • 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)
  • Serious adverse events [ Time Frame: Day 28 ]
    Serious adverse events
  • Adverse events resulting in treatment discontinuation [ Time Frame: Day 28 ]
    Adverse events
  • Adverse events considered related to the investigational products [ Time Frame: Day 28 ]
    Related adverse events
  • 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
  • Maximum score on WHO Ordinal Scale for Clinical Improvement during study participation [ Time Frame: Day 28 ]
    score 0(Uninfected)~ score 8(Dead)
  • Cumulative incidence of hospitalization [ Time Frame: Day 28 ]
    frequency of patients requiring time in hospital
  • Days of hospitalization [ Time Frame: Day 28 ]
    length of hospital stay
  • Cumulative incidence of mortality [ Time Frame: Day 28 or later if participant is hospitalized at the time of Day 28 ]
    incidence of death
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE COVID-19 Treatment in South Africa
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Other: Standard of care (Paracetamol)
    SOC - 2 tablets (1000 mg) to be taken 6-hourly as needed
  • Drug: Artesunate-amodiaquine
    SOC plus artesunate-amodiaquine (ASAQ) - 2 tablets (200/540 mg artesunate/amodiaquine) daily for 3 days
  • 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
  • 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
  • Drug: Sofosbuvir/daclatasvir

    SOC plus sofosbuvir/daclatasvir (SOF/DCV)

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

Study Arms  ICMJE
  • Placebo Comparator: Arm A
    Paracetamol (SOC)
    Intervention: Other: Standard of care (Paracetamol)
  • Experimental: Arm B
    SOC plus Artesunate-Amodiaquine
    Intervention: Drug: Artesunate-amodiaquine
  • Experimental: Arm C
    SOC plus Pyronaridine-Artesunate
    Intervention: Drug: Pyronaridine-artesunate
  • Experimental: Arm D
    SOC plus Favipiravir plus Nitazoxanide
    Intervention: Drug: Favipiravir plus Nitazoxanide
  • Experimental: Arm E
    SOC plus Sofosbuvir/daclatasvir
    Intervention: Drug: Sofosbuvir/daclatasvir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 16, 2021)
192
Original Estimated Enrollment  ICMJE
 (submitted: August 28, 2020)
250
Actual Study Completion Date  ICMJE August 23, 2021
Actual Primary Completion Date August 5, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04532931
Other Study ID Numbers  ICMJE SP-PA-COV-202
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Shin Poong Pharmaceutical Co. Ltd.
Study Sponsor  ICMJE Shin Poong Pharmaceutical Co. Ltd.
Collaborators  ICMJE Medicines for Malaria Venture
Investigators  ICMJE Not Provided
PRS Account Shin Poong Pharmaceutical Co. Ltd.
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP