Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202303499747084 Date of Registration: 29/03/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A Phase 3, multicenter, randomized, double-blind, 24-week study of the clinical and antiviral effect of S-217622 compared with placebo in non-hospitalized participants with COVID-19
Official scientific title A Phase 3, multicenter, randomized, double-blind, 24-week study of the clinical and antiviral effect of S-217622 compared with placebo in non-hospitalized participants with COVID-19
Brief summary describing the background and objectives of the trial DESIGN ACTIV-2d/A5407 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of S-217622 for the treatment of symptomatic non-hospitalized adults with high and low risk of progression to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. REGIMEN S-217622 or placebo orally once daily for 5 days (375 mg on Day 1 followed by 125 mg on Days 2 to 5). DURATION Days 1 through 29 intensive study, followed by limited study through 24 weeks. STRATIFICATION Randomization will be stratified by geographic region and high risk versus (vs.) low risk of severe coronavirus disease 2019 (COVID-19) POPULATION Outpatient adults (≥18 years) with: a) documented positive SARS-CoV-2 nucleic acid or antigen test from a sample collected ≤120 hours (5 days) prior to randomization, b) onset of symptoms of COVID-19 ≤5 days prior to randomization, c) presence of 1 or more select COVID-19 symptoms within 24 hours prior to randomization. Participants will be eligible regardless of vaccination status and will be classified as either high risk or low risk. High-risk participants: defined as aged ≥65 years or those with presence of high-risk conditions. Low-risk participants: defined as those not meeting the high-risk definition. SAMPLE SIZE Approximately 1490 participants (745 on S-217622 and 745 on placebo) will be randomized into the study. Approximately 50% of enrollment will be high-risk participants and 50% will be low-risk participants. All locally provided standard-of-care, including COVID-19 monoclonal antibody (mAb) treatment, outpatient intravenous (IV) remdesivir, and oral antivirals compatible with S-217622 will be permitted after enrollment, in addition to the randomized treatment. OUTCOME MEASURES The primary outcome measure is: Time in days from the start of S-217622 to sustained symptom resolution.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SCORPIO HR
Disease(s) or condition(s) being studied Covid 19,Respiratory
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 31/10/2022
Actual trial start date 10/01/2023
Anticipated date of last follow up 31/12/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 1490
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
ACTIV2dA5407 Shionogi
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group S 217622 S-217622 orally once daily for 5 days (375 mg on Day 1 followed by 125 mg on Days 2 to 5) 5 days Active group 745
Control Group Placebo Placebo orally once daily for 5 days (375 mg on Day 1 followed by 125 mg on Days 2 to 5) 5 days Placebo group 745 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Age ≥18 year - Documentation of laboratory-confirmed active SARS-CoV-2 infection, as determined by a nucleic acid (e.g., reverse-transcriptase PCR) or antigen test from any respiratory tract specimen (e.g., oropharyngeal, NP or nasal swab, or saliva) collected ≤120 hours (5 days) prior to randomization. - Participants are expected to begin study intervention ≤5 days from self-reported date of onset of any of the COVID-19-related symptoms from the following list:  Cough  Shortness of breath or difficulty breathing  Feeling feverish  Chills  Fatigue  Body pain or muscle pain or aches  Diarrhea  Nausea  Vomiting  Headache  Sore throat  Nasal obstruction or congestion  Nasal discharge  Loss of taste or smell One or more of the following signs/symptoms present within 24 hours prior to randomization (all criteria above except loss of taste or smell):  Cough  Shortness of breath or difficulty breathing  Feeling feverish  Chills  Fatigue  Body pain or muscle pain or aches  Diarrhea  Nausea  Vomiting  Headache  Sore throat  Nasal obstruction or congestion  Nasal discharge - Oxygenation saturation of ≥92% on room air - Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period unless meeting hospitalization criteria or reaching Day 29, whichever is earliest - For participants who are of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to randomization. - History of hospitalization for the current SARS-CoV-2 infection (i.e., prior hospitalization for a prior episode of SARS-CoV-2 infection is allowable). - For the current SARS-CoV-2 infection, any positive SARS-CoV-2 molecular (nucleic acid) or antigen test from any respiratory tract specimen (e.g., oropharyngeal, NP or nasal swab, or saliva) collected ˃120 hours (5 days) prior to randomization. Participants with reinfection, defined as prior SARS-CoV-2 infection that began >90 days prior to the current onset of symptoms with interval resolution of symptoms are eligible as long as the current infection has not been present for more than 5 days prior to randomization. - Current need for hospitalization or immediate medical attention in the opinion of the investigator. - Current use of any medications prohibited with the study intervention. Use of Paxlovid at any time and the use of any oral, inhaled, or injectable medication intended to treat symptomatic SARS-CoV-2 infection before enrollment are excluded. After enrollment, locally available SARS-CoV-2 treatment (including but not limited to molnupiravir, mAbs, outpatient IV remdesivir, convalescent plasma, inhaled budesonide, favipiravir, and fluvoxamine) will be permitted, as long as there are no concerns for DDIs. - Receipt of any investigational treatments for the current episode of SARS-CoV-2 at any time prior to randomization is exclusionary. - Any comorbidity requiring surgery within 7 days prior to randomization or that is considered life threatening in the opinion of the investigator within 28 days prior to randomization. Currently pregnant or breastfeeding. - Known allergy/sensitivity or any hypersensitivity to components of S-217622 or placebo for S-217622. - Known current renal impairment defined as CrCl <30 mL/min by Cockcroft-Gault or requiring dialysis. - Known history of cirrhosis or liver decompensation (including ascites, variceal bleeding, or hepatic encephalopathy) 80 and over: 80+ Year,Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 80 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/06/2022 Pharma Ethics
Ethics Committee Address
Street address City Postal code Country
PO Box 786 Irene Centurion 0062 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 12/10/2022 Wits Ethics
Ethics Committee Address
Street address City Postal code Country
corner Wits Health Consortium Ltd, 8 Blackwood Avenue, Parktown Johannesburg 2193 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 21/10/2022 Infectious Disease Institute Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Mulago Hill Road, Near Mulago Hospital Complex Kampala 0000 Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 15/12/2022 Kintampo Health Research Centre
Ethics Committee Address
Street address City Postal code Country
Hospital Road Kintampo B/A Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 25/10/2022 Navrongo Health Research Centre
Ethics Committee Address
Street address City Postal code Country
Behind Navrongo War Memorial Hospital Navrongo 114 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 13/12/2022 AMREF
Ethics Committee Address
Street address City Postal code Country
PO BOX 31025-00100 Nairobi n/a Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 18/01/2023 NHSRC Approval Dr Mponda
Ethics Committee Address
Street address City Postal code Country
PO Box 30377 Lilongwe n/a Malawi
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/02/2023 MRTH MU Research Ethics Commitee
Ethics Committee Address
Street address City Postal code Country
PO Box 3 Eldoret 3010 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 08/02/2023 Moi Teaching and Referral Hospital
Ethics Committee Address
Street address City Postal code Country
Moi Teaching and Referral Hospital Eldoret 30100 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 27/01/2023 NHSRC Approval for Dr C Kanyama
Ethics Committee Address
Street address City Postal code Country
PO Box 30377 Lilongwe 0000 Malawi
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 23/01/2023 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
20 Cambridge Road Harare 0000 Zimbabwe
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 10/03/2023 Ifakara Health Ethics review Board
Ethics Committee Address
Street address City Postal code Country
PO Box 78373 Dar Es Salaam 0000 Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 27/02/2023 Mbeya Medical Research and Ethics Commitee
Ethics Committee Address
Street address City Postal code Country
PO Box 2410 Mbeya 0000 Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 08/03/2023 Kilimanjaro Christian Medical Centre ethics Commitee
Ethics Committee Address
Street address City Postal code Country
Box 2240 Kilimanjaro 0000 Tanzania
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome TComposite Outcome: Hospitalization From Any Cause or Death From Any Cause Day 29
Secondary Outcome Percentage of Participants With Adjudicated Hospitalization Due to COVID-19 or Death Due to Any Cause Up to Day 29
Secondary Outcome Percentage of Participants With Nasopharyngeal (NP) SARS-CoV-2 RNA Below the Lower Limit of Quantification (LLoQ) on Days 4 and 8 Days 4 and 8
Secondary Outcome Median Change From Baseline of SARS-CoV-2 RNA in NP Swabs on Days 4 and 8 Days 4 and 8
Secondary Outcome Percentage of Participants With Undetectable Viral Culture From Nasopharyngeal Samples on Days 4 and 8 Days 4 and 8
Secondary Outcome Median Time to Sustained Symptom Improvement Up to Day 29
Secondary Outcome Median Time to Self-reported Return to Usual (Pre-COVID-19) Health Up to Day 29
Secondary Outcome Percentage of Participants at Each Clinical Status as Assessed by a 7-Point Ordinal Scale Day 29
Secondary Outcome Percentage of Participants With Resting Peripheral Oxygen Saturation ≥96% Up to Day 29
Secondary Outcome Number of Participants With Adverse Events Up to Week 48
Secondary Outcome Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Quality of Life Score Baseline, Week 48
Secondary Outcome Change From Baseline in EuroQol 5 Dimension 5 Level Index Score Baseline, Week 48
Secondary Outcome hange From Baseline in Pose-acute COVID-19 Questionnaire hange From Baseline in Pose-acute COVID-19 Questionnaire
Secondary Outcome Percentage of Participants Who Experienced Death Due to Any Cause Up to Week 48
Secondary Outcome Plasma Concentration of S-217622 60 and 90 minutes postdose on Day 1 and predose on Day 4
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Clinical HIV Research Unit University of Witwatersrand, Clinical HIV Research Unit, Themba Lethu Clinic, Helen Joseph Hospital, Perth Road, Westdene Johannesburg 2006 South Africa
Perinatal HIV Research Unit New Nurses Home, Chris Hani Baragwanath Academic Hospital, Chris Hani Road. Soweto 1862 South Africa
TASK Eden Research Centre 4 Victoria Road George 6529 South Africa
Be Part Research 4 Madikane Street, Mbekweni. Paarl 7626 South Africa
Josha Research 28 East Burger Street Bloemfontein 9300 South Africa
Worthwhile Clinical Trials Lakeview Hospital, 1 Mowbray Avenue, Benoni 1500 South Africa
Limpopo Clinical Research Initiative 11 Van Der Bijl Street, Tamboti Medical Centre, Floor 1 Thabazimbi 0380 South Africa
Global Clinical Trials Pretoria Shop 29 Nedbank Plaza, 175 Steve Biko Street, Pretoria 0001 South Africa
Medicross Roodepoort Clinical Research 54 Ontdekkers Road, Princess crossing Roodepoort 1724 South Africa
Dr A Jacovides and Partners Health Emporium, Midrand Medical Centre, Shop no1, Corner Market and Church Street, Halfway House Midrand 1685 South Africa
Right to Care Research Esizayo Right Clinic Esizayo, Corner Malibongwe Drive and Tennessee Avenue, Kya Sands Johannesburg South Africa
Ubuntu Clinical Research Krugersdorp 71 Pretoria Street Krugersdorp South Africa
Ubuntu Clinical Research Lenasia 212 Rose Avenue Johannesburg South Africa
The Aurum Institute Rustenburg 178 Beyers Naude Drive Rustenburg South Africa
NAVRONGO HEALTH RESEARCH CENTRE BEHIND WAR MEMORIAL HOSPITAL P.O. BOX114, NAVRONGO Ghana
Kintampo Health REesearch Centre Ministry of Health, No.2 Health Loop, P. O. Box 200 Kintampo Ghana
Kumasi Centre for Collaborative Research into Tropical Medicine South End Asuogya Road, Kwame Nkrumah University of Science and Technology Kumasi Ghana
Infectious Diseases Institute Makerere University College of Health Sciences, Mulago Hill Road, near Mulago Hospital Complex Kampala Uganda
Infectious diseases research collaboration Tororo General Hospital, IDRC clinic PO Box 2 Tororo Uganda
Strengthening Institutional Capacity for Research Administration Lira Regional Referral Plot 21-41 Ngetta Road Lira Uganda
JOINT CLINICAL RESEARCH CENTRE Lubowa site Plot 101 Lubowa Estates, off Entebbe Road Kampala Uganda
Kenyatta National Hospital Hospital Road, Nairobi Kenya
Kenya Medical Research Institute US Army Medical Research Directorate Kenya American Embassy P.O. Box 606 Village market United Nations Avenue Nairobi Kenya
KEMRI CCR Butere County Hospital Butere County Hospital opposite Butere Girls High School Butere Kenya
Moi University Clinical Research Centre 2nd Floor, Chandaria Chronic Disease and Cancer Centre Moi Teaching and Referral Hospital Eldoret Kenya
Victoria Biomedical Research Institute Kisumu County Referral Hospital, P.O. Box 7180 Kisumu Kenya
AHERO CLINICAL TRIALS UNIT AHERO COUNTY HOSPITAL, ALONG KISUMU NAIROBI HIGHWAY Kisumu Kenya
UNC Project Private Bag A-104 Lilongwe Malawi
Mangochi PHNG Study Site C/O Professor Ken Maleta, Kamuzu University of Health Sciences Chichiri Malawi
Johns Hopkins Research Project Queen Elizabeth Central Hospital, Chipatala Avenue Blantyre Malawi
Kilimanjaro Christian Medical Centre PO Box 152 Moshi United Republic of Tanzania
Ifakara Health Institute PO Box 78373 Dar Es Salaam 00000 United Republic of Tanzania
NIMR Mbeya Medical Research Centre Hospital Hill Road, PO Box 2410 Mbeya 00000 United Republic of Tanzania
National Institute for Medical Research Mwanza Centre D12126/6386 Isamila Road P.O Box 1462 Mwanza 0000 United Republic of Tanzania
UZCHS CTRC Milton Park CRS University of Zimbabwe College of Health Sciences Clinical Trials Research Centre 31 Lawson Ave, Milton Park Harare 00000 Zimbabwe
Seke North Clinical Research Site 15 Phillips Avenue,Belgravia Harare 0000 Zimbabwe
UZCHS CTRC St Marys CRS Chitungwiza Primary Care Clinic ,University of Zimbabwe College of Health Sciences,Clinical Trials Research Centre Chitungwiza 0000 Zimbabwe
Spilhaus Clinical Research Site Sally Mugabe Hospital Grounds,Highfield Road, Southerton Harare 00000 Zimbabwe
UZCHS CTRC Seke South CRS Seke South Clinic,University of Zimbabwe College of Health Sciences,Clinical Trials Research Centre Chitungwiza 00000 Zimbabwe
Harare Family Care Clinical Research Site Parirenyatwa Hospital, Mazowe Street Harare 0000 Zimbabwe
Zengeza Clinical Research Site 7723 Cheuka Street,Zengeza 3 Clinic,Mashonaland East Chitungwiza 00000 Zimbabwe
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institute of Allergy and Infectious Diseases 5601 Fishers Lane Room 2D40 Rockville MD 20892 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Shionogi Inc 300 Campus Drive, Florham Park NJ 07932 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Elizabeth Hellstrom Louw pi@bepart.co.za +27218683990 4 Madikane Street, Mbekweni
City Postal code Country Position/Affiliation
Paarl 7626 South Africa National PI South Africa
Role Name Email Phone Street address
Public Enquiries Michelle Botha michelle.botha@iqvia.com +27828888132 IAVIA, 1021 Lenchen avenue north corner of John Vorster drive.
City Postal code Country Position/Affiliation
Centurion 0062 South Africa Associate Director Sub Saharan Africa Country Site Activation
Role Name Email Phone Street address
Scientific Enquiries Simon Portsmouth simon.portsmouth@shionogi.com +18627774269 300 Campus Drive, Florham Park
City Postal code Country Position/Affiliation
NJ 07932 United States of America Shionogi Representative
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Sponsor/ACTG is committed to responsible data sharing regarding the clinical trials they sponsor. It is the policy of the ACTG to publish and share research results in a timely manner in accordance with the NIH Public Access Policy http://publicaccess.nih.gov/policy.htm. It is also the policy of the ACTG to publish the results of the main study/project primary manuscript prior to those of substudies and secondary manuscripts, unless otherwise approved by the Scientific Agenda Steering Committee (SASC). This policy is expected to be followed for ACTG studies, collaborative studies with cosponsoring agencies or other clinical trials networks, and studies in which data are collected and analyzed by a network or group other than the ACTG Statistical and Data Management Center (SDMC), unless alternative policies are mutually agreed upon and codified in the Clinical Trials Agreement (CTA), Letter of Understanding (LOU), or Memorandum of Understanding (MOU), or otherwise approved by the ACTG Executive Committee (AEC). Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), or the AEC, with DAIDS/NIAID approval, have authority to embargo any/all information in Executive Summaries and accompanying documents, CTU/CRS Scientific Summaries, Participant Summaries, and press releases, until information is made public (i.e., abstract presentation or manuscript publication). Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol This will be done within 12 months of the study completion date. Access is provided after a research proposal is submitted and has received approval from the review panel and after Data Sharing Agreement is in place.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information