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 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202403575006415 Date of Approval: 20/03/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title MK8591A-053 A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in HIV-1 Infected Treatment-Naïve Participants (MK8591A-053)
Official scientific title A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity,Safety, and Tolerability of Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in HIV-1 InfectedTreatment-Naïve Participants (MK8591A-053)
Brief summary describing the background and objectives of the trial Current standard-of-care for the treatment of HIV-1 is a combination of 2 NRTIs with a third agent (eg, InSTI, NNRTI, or PI). People living with HIV-1 receiving effective ART regimens can expect to live near-normal lifespans. As this population ages, there is increasing concern about polypharmacy, long-term toxicity, and DDIs related to comorbidity and multimorbidity and risks associated with the emergence of HIV-1 variants resistant to InSTI, NRTI, and NNRTI treatments. There is a need for simpler and safer regimens, that reduce overall drug exposure. There is evidence that 2-drug regimens can achieve efficacy comparable to that of 3-drug regimens, offer better tolerability, and improve quality of life The primary objective of the trial is to evaluate the antiretroviral activity and the safety and tolerability of DOR/ISL compared to BIC/FTC/TAF, asassessed by the percentage of participants with HIV-1 RNA <50 copies/mL at Week 4.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 28/03/2023
Actual trial start date
Anticipated date of last follow up 09/01/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 110
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL www.msd.co.za
Secondary Ids Issuing authority/Trial register
MK8591A 053 PACTR
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 Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group doravirine and islatravir 100mg/0.25mg Day 1 to Week 96 Pink oval shaped bi-convexand debossed with “772”symbols on one side and isplain on the other side. 27
Experimental Group Placebo to bictegraviremtricitabine tenofoviralafenamide 0 mg Day 1 to Week 96 BIKTARVY (BIC) is a fixed dose combination tabletcontaining bictegravir (BIC),emtricitabine (FTC), andtenofovir alafenamide (TAF)for oral administration. 28
Control Group bictegravir emtricitabinetenofovir alafenamide 50 mg 200mg 25 mg Day 1 to Week 96 BIKTARVY (BIC) is a fixed dose combination tabletcontaining bictegravir (BIC),emtricitabine (FTC), andtenofovir alafenamide (TAF)for oral administration. 27 Active-Treatment of Control Group
Control Group Placebo to doravirineislatravir 0 mg Day 1 to Week 96 Pink oval shaped bi-convexand debossed with “772”symbols on one side and isplain on the other side. 28 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Is HIV-1 positive with plasma HIV-1 RNA ≥500 copies/mL at screening. 2.Is naïve to ART defined as havingreceived no prior therapy with anyantiretroviral agent following adiagnosis of HIV-1 infection. 3. Is anindividual of any sex/gender, at least18 years of age, at the time ofproviding documented informedconsent. 4. A participant assignedfemale sex at birth is eligible toparticipate if not pregnant orbreastfeeding. 5. The participant (orlegally acceptable representative)has provided documented informedconsent for the study. Theparticipant may also provideconsent for FBR. However, theparticipant may participate in thestudy without participating in FBR. 1. Has HIV-2 infection. 2. Hashypersensitivity or othercontraindication to any of thecomponents of the studyinterventions as determined by theinvestigator. 3.Has a diagnosis of anactive AIDS-defining opportunisticinfection within 30 days prior toscreening. 4. Has active HBVinfection (defined as HBsAg-positiveor HBV DNA-positive). 5. Haschronic HCV infection (detectableHCV RNA) with laboratory valuesconsistent with cirrhosis (serumalbumin <2.8 g/dL or INR >1.7 orplatelets <100 x 109 cells/L). 6. Hasa history of malignancy ≤5 yearsprior to providing documentedinformed consent except foradequately treated basal cell orsquamous cell skin cancer, in situcervical cancer, or cutaneousKaposi’s sarcoma. 7. Has a historyor current evidence of any condition(including active tuberculosisinfection), therapy, laboratoryabnormality, or other circumstance(including drug or alcohol use ordependence) that might, in theopinion of the investigator, confoundthe results of the study or interferewith the participant’s participation forthe full duration of the study, suchthat it is not in the best interest ofthe participant to participate. 8.Hasbeen treated for a viral infectionother than HIV-1, such as hepatitisB, with an agent that is activeagainst HIV-1, including, but notlimited to, the following: adefovir,TDF, TAF, FTC, or 3TC. 9.Is takingor is anticipated to require systemicimmunosuppressive therapy,immune modulators, or strong andmoderate CYP3A inducers (or anyother prohibited therapies outlined inSection 6.5) from 45 days prior toDay 1 through the study treatmentperiod. 10. Is currently participatingin or has participated in a clinicalstudy and received (or is receiving)an investigational compound ordevice from 45 days prior to Day 1through the study treatment period. 11. Has a documented or knownvirologic resistance to any approvedHIV-1 reverse transcriptase inhibitor,or any study intervention. 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ 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 04/08/2023 University of Cape Town Faculty of Health Sciences Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Anzio Road, Groote Schuur Hospital Cape Town 7925 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 19/02/2024 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840-00200 Nairobi 00100 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 26/06/2023 University of Stellenbosch HREC
Ethics Committee Address
Street address City Postal code Country
University of Stellenbosch, Matieland Stellenbosch 7606 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 11/05/2023 University of the Witwatersrand Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace Parktown 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 03/03/2024 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
P.O. Box 54840-00200 Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1.Percentage of participants with HIV-1 RNA <50copies/mL 2.Percentage of participants whoexperience AEs and percentage of participants whodiscontinue study intervention due to AEs Week 48
Secondary Outcome 1. Percentage of participants with HIV-1 RNA <50copies/mL 2. Percentage of participants with HIV-1RNA <200 copies/mL at 3. Mean change frombaseline in CD4+ T-cell count 4. Viral resistance-associated substitutions 5. Mean change frombaseline in weight 6. General safety and tolerability Week 48, Week 96 and through study duration
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI CMR RCTP Agoi Street Kisumu 40100 Kenya
PHRD KEMRI Partners in Health Research and Development Section 9 OAU Road Nairobi 00200 Kenya
CCR KEMRI Center for Clinical Research Mbagathi Road Off Raila Odinga Way Nairobi 00200 Kenya
Enhancing Care Foundation Wentworth Provincial Hospital Sidmouth Avenue Durban 4052 South Africa
JOSHA Research East Burger Street Bloemfontein 9301 South Africa
Perinatal HIV Research Unit PHRU Chris Hani Road Johanessburg 1864 South Africa
Be Part Yoluntu Centre 4 Madikane Street Paarl 7626 South Africa
Ezintsha 32 Princess of Wales Terrace Johannesburg 2193 South Africa
WITS Clinical HIV Research Unit Perth Road Helen Joseph Hospital Johannesburg 2041 South Africa
Desmond Tutu Health Foundation Clinical Trial Unit Main Road Observatory Cape Town 7925 South Africa
Qhakaza Mbokodo Research Clinic 15 Park Lane LadySmith 3370 South Africa
Madibeng Centre for Research 40 Pienaar Street Brits 0250 South Africa
Human Sciences Research Council Centre for Community Based Research Caluza Road Mvubukazi 3201 South Africa
Family Clinical Research Unit Francie Van Zijl Drive Cape Town 2092 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
MSD 16th Road Midrand 1685 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor MSD Pty Ltd 16th Road Midrand 1685 South Africa Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Zoe Nell zoe.nell@msd.com +276553307 16th Road
City Postal code Country Position/Affiliation
Midrand 1685 South Africa Clinical ResearchDirector
Role Name Email Phone Street address
Scientific Enquiries Sheetal Kassim Sheetal.kassim@hiv-research.org.za 0027214066960 Main Road
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa National PI South Africa
Role Name Email Phone Street address
Principal Investigator Rosie Mngqibisa Rosie@ecarefoundation.com 00272611093 Sidmouth Avenue
City Postal code Country Position/Affiliation
Durban 4052 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Sharne Foulkes sharne.foulkes@josha.co.za 0027514128160 28 East Burger Street
City Postal code Country Position/Affiliation
Bloemfontein 9301 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Lerato Mohapi mohapil@phru.co.za 0027119899700 Chris Hani Road
City Postal code Country Position/Affiliation
Johannesburg 1864 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Elizabeth Hellstrom pi@bepart.co.za 00270218683990 4 Madikane Street
City Postal code Country Position/Affiliation
Paarl 7626 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Simiso Sokhela ssokhela@ezintsha.org 0027110844933 32 Princess of WalesTerrace
City Postal code Country Position/Affiliation
Johannedburg 2193 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Noluthando Mwelase tmwelase@witshealth.co.za 0027112768800 Perth road
City Postal code Country Position/Affiliation
Johannesburg South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Elizabeth Bukusi ebukusi@kemri.org +27733617503 614 Agoi Street
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Principal Investigator
Role Name Email Phone Street address
Principal Investigator Nelly Mugo rwamba@uw.edu +254733629665 Partners in Health Research andDevelopment and Center for ClinicalResearch CCR, Kenya MedicalResearch Institute KEMRI
City Postal code Country Position/Affiliation
Nairobi 00202 Kenya Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Elizabeth Bukusi ebukusi@kemri.org +27733617503 614 Agoi Street
City Postal code Country Position/Affiliation
Kisumu 40100 Kenya Coordinating PI Kenya
Role Name Email Phone Street address
Principal Investigator Philippus Kotze plkotze@gmail.com +27824588969 15 Park Lane
City Postal code Country Position/Affiliation
LadySmith 3370 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Cheryl Louw clouw@madibengresearch.co.za +27824149433 40 Pienaar Street
City Postal code Country Position/Affiliation
Brits 0250 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Shannon Bosman sbosman@hsrc.ac.za +27826347680 Caluza Road
City Postal code Country Position/Affiliation
Mvubukazi 3201 South Africa Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes MSD is fully committed to supporting the EFPIA and PhRMA guiding principles on data sharing, including the principle of providing qualified scientific researchers access to anonymized participant-level data and full clinical study reports (CSRs) from MSD’s clinical trials to conduct legitimate scientific research. We are also fully participating in the Institutes of Medicine (IOM) global effort to develop principles for responsible sharing of clinical trial data. Scope of Data: MSD will provide access to participant-level data and CSRs from clinical trials performed by MSD for which results are posted on the clinicaltrials.gov registry (dating back to September 2007) for products or indications that have been approved by regulators in the US and EU. In general, data will be made available for request approximately 18 months after clinical trial completion. Data from phase I trials in healthy volunteers and consumer health care studies are out of scope for this procedure. Plan and Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol From study start until end of retention period as per MSD Policy period which is aligned with ICH GCP. IPD will be provided for: 1. GCP Inspections 2. Market approval audits 3. Other inspections 4. Ethics Committee Inspections N other data will be shared.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
www.msd.co.za 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