South African National Clinical Trials Registry
South African Medical Research Council, Cochrane South Africa
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: sactradmin@mrc.ac.za Website: sanctr.samrc.ac.za
Trial no.: DOH-27-012024-5509 Date of Approval: 19/01/2024
Trial Status: Approved
TRIAL DESCRIPTION
Public title MK8527-007 Safety and Pharmacokinetic Study of Oral MK-8527 QM in Participants at Low-Risk for HIV-1 Infection
Official scientific title MK8527-007 A Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral MK-8527 Once Monthly in Participants at Low- Risk for HIV-1 Infection
Brief summary describing the background and objectives of the trial MK-8527 is a novel deoxyadenosine analog with potent antiviral activity being developed for the prevention of HIV-1 infection. This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multicenter study of oral MK-8527 administered QM in adults who are at low-risk of HIV-1 infection. The main objectives of this study are to characterize the safety, tolerability, and PK of MK-8527 in a larger and more diverse population than studied to date. The study will enroll participants who are not infected with HIV-1 and are at low-risk of HIV-1 infection. According to CDC and WHO guidelines [Centers for Disease Control and Prevention 2018] [World Health Organization 2015], persons who are at substantial risk of HIV-1 infection should be referred for local HIV prevention services that may include PrEP, for which there are approved products (FTC/TDF, FTC/TAF, or cabotegravir IM). Population PK predictions based on clinical data to date indicate that MK-8527 6 mg to 8 mg QM will achieve threshold levels against wild-type virus for HIV-1 prevention that would last at least 4 weeks. Participants will be followed for 8 weeks after the last dose of MK-8527 to allow for full characterization of the MK-8527-TP PK profile. The number of participants (N=~350), the inclusion of a placebo group, and the 6 QM doses allow for characterization of the safety profile of MK-8527 before the initiation of Phase 3 prevention efficacy studies. To ensure a study population that is representative of individuals most at risk for HIV-1 infection and corresponding to the demographics for the target population of the Phase 3 efficacy studies, the study population will comprise 30% women, 30% men, 80% of participants aged 35 years, and 30% enrolled in Africa.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) II
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 12/01/2024
Actual trial start date 25/01/2024
Anticipated date of last follow up 18/03/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 110
Actual target sample size (number of participants) 119
Recruitment status Active, not recruiting
Publication URL www.msd.co.za
Secondary Ids Issuing authority/Trial register
MK8527-007 Sponsor
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 Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification 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 MK8527 3mg QM Day 1 to Week 20 MK-8527 is a novel deoxyadenosine analog with potent antiviral activity being developed for the prevention of HIV-1 infection. 27
Experimental Group MK8527 6mg QM Day 1 to Week 20 MK-8527 is a novel deoxyadenosine analog with potent antiviral activity being developed for the prevention of HIV-1 infection. 27
Experimental Group MK8527 12mg QM Day 1 to Week 20 MK-8527 is a novel deoxyadenosine analog with potent antiviral activity being developed for the prevention of HIV-1 infection. 27
Control Group Placebo 0mg QM Day 1 to Week 20 Placebo to MK8527 29 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Is confirmed HIV-uninfected based on negative HIV-1/HIV-2 test result before randomization 2. Has low-risk of HIV infection, defined as all of the following within 12 months prior to the screening visit or the rescreening visit 3. Is an individual of any sex/gender, from 18 years to 65 years of age inclusive, at the time of providing the informed consent. 4. If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate study intervention after the last dose of study intervention. The length of time required to continue contraception for study intervention is: 8 weeks after the last dose of blinded study intervention. 5. A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding 6. The participant (or legally acceptable representative) has provided documented informed consent for the study. 1. Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator. 2. Has an active diagnosis of hepatitis due to any cause, including active HBV infection (defined as HBsAg-positive) or HCV infection (defined as detectable HCV RNA). 3. Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. 4. Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate. 5. Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies outlined in Section 6.5 from 30 days prior to Day 1 through the duration of the study. 6. Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days prior to Day 1 through the duration of the study. 7. Has previously received MK-8527 or MK-8591 8. Has QTc intervals (using Fridericia correction) >450 msec (for males) or >460 msec (for females) or deemed clinically abnormal by the investigator. 9. Has exclusionary laboratory values within 45 days prior to Day 1 10. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study. Adult: 19 Year(s)-105 Year(s) 18 Year(s) 90 Year(s) Both
APPROVALS
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 07/11/2023 SAHPRA
Ethics Committee Address
Street address City Postal code Country
Building A Loftus Park 2nd Floor 402 Kirkness Street Pretoria 0001 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 12/12/2023 University of the Witwatersrand Human Research Ethics Committee Medical
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace Parktown 2041 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 13/12/2023 Pharma Ethics
Ethics Committee Address
Street address City Postal code Country
123 Amkor Road Lyttelton Manor 0157 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 04/03/2024 University of Cape Town HREC
Ethics Committee Address
Street address City Postal code Country
E 53 Room 46, Old Main Building, Groote Schuur Hospital, Observatory Cape Town 7925 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • Adverse events • Adverse events leading to discontinuation of study intervention Day 1 to Week 20
Secondary Outcome • MK-8527 AUC 0-last and C max Day 1 to Week 20
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University of the Witwatersrand Clinical HIV Research Unit Perth Road Johannesburg 2041 South Africa
JOSHA Research 28 East Burger Street Bloemfontein 9300 South Africa
Qhakaza Mbokodo Research Clinic 15 Parklane Mkhamba Gardens Ladysmith 3370 South Africa
Wits RHI Ward 21 Clinical Research Site 22 Esselen Street Hillbrow 2001 South Africa
Desmond Tutu Health Foundation Clinical Trials Unit Main Road Observatory 7925 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
MSD Pty Ltd 117 - 16th Road Halfway House 1685 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor MSD Pty Ltd 117 16th Road Halfway House 1685 South Africa Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries LG Bekker Linda-Gail.Bekker@hiv-research.org.za +27216506966 Main Road
City Postal code Country Position/Affiliation
Observatory 7925 South Africa National Principal Investigator and Professor at UCT
Role Name Email Phone Street address
Public Enquiries U Bridgmohun urmilla.bridgmohun1@msd.com +27116553400 117 16th Road
City Postal code Country Position/Affiliation
Halfway House 1685 South Africa Therapeutic Area Head
Role Name Email Phone Street address
Principal Investigator MS Rassool mrassool@witshealth.co.za +27112768800 Perth Road
City Postal code Country Position/Affiliation
Westdene 2041 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator JJ Lombaard josha.research@power4u.co.za +27514128160 28 East Burger Street
City Postal code Country Position/Affiliation
Bloemfontein 9300 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator PL Kotze plkotze@gmail.com +27366312372 15 Parklane Mkhamba Gardens
City Postal code Country Position/Affiliation
Ladysmith 3370 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator N Poovan npoovan@wrhi.ac.za +27113585300 22 Esselen Street
City Postal code Country Position/Affiliation
Hillbrow 2001 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator Y Singh Yashna.singh@hiv-research.org.za +27214066958 Main Road
City Postal code Country Position/Affiliation
Observatory 7925 South Africa Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes IPD will not be provided to the public. IPD will be shared with representatives from government agencies such as the South Africa health Products Regulatory Authority (SAHPRA), the National Health Research Ethics Council (NHREC) and relevant Ethics Committees. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol From study start until end of retention period as MSD Policy period which is aligned with SA GCP. 6-months after study completion (180 days) IPD will be provided for: 1. GCP Inspections 2. Market approval audits 3. Other inspections 4. Ethics Committee inspections No 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
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 04/03/2024 Added actual start date 25 Jan 2024
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 30/05/2024 updated with the total number of participants randomised in to the trial. 119
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 04/03/2024 Change to indicate that recruiting started Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 30/05/2024 Recruitment for the study is closed and the trial is active and ongoing. Recruiting Active, not recruiting
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 02/01/2024 The primary safety assessment will include all accumulated safety data through the last follow-up visit. AEs leading to discontinuation from study intervention are assessed until Week 20 (last dose received). Safety and tolerability will be assessed by clinical review of all relevant parameters including AEs and laboratory test results. The primary objective of the study is to evaluate the safety and tolerability of oral MK-8527 in a population with low-risk of HIV-1-infection. Primary Outcome, • Adverse events • Adverse events leading to discontinuation of study intervention , 28 weeks Primary Outcome, • Adverse events • Adverse events leading to discontinuation of study intervention , 20 weeks
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 02/01/2024 The main objectives of this study are to characterize the safety, tolerability, and PK of MK-8527 in a larger and more diverse population than studied to date. The study will enroll participants who are not infected with HIV-1 and are at low-risk of HIV-1 infection. To ensure adequate safety profile. This is a safety and tolerability study. Primary Outcome, • Adverse events • Adverse events leading to discontinuation of study intervention , 20 weeks Primary Outcome, • Adverse events • Adverse events leading to discontinuation of study intervention , Day 1 to Week 20
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 02/01/2024 An interim safety analysis will be performed once 50% of the planned enrollment has reached Week 12 or discontinued from study intervention. Evaluation of MK-8527 plasma levels is necessary to ensure target threshold levels are achieved, in support of dose selection for future Phase III prevention efficacy trials, and to allow full characterization of the MK-8527 PK profile. PK Plasma will be collected on Day 1, Day 2, Week 20 (EOT) and Follow-up Visit 1 Secondary Outcome, • MK-8527 AUC 0-last and C max, Week 12 Secondary Outcome, • MK-8527 AUC 0-last and C max, Day 1 to Week 20
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 19/03/2024 Added site after receiving initial EC approval Desmond Tutu Health Foundation Clinical Trials Unit, Main Road, Observatory, 7925, South Africa
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 18/12/2023 Added initial Pharma-Ethics approval True, Pharma Ethics, 123 Amkor Road, Lyttelton Manor, 0157, South Africa, , 13 Dec 2023, +27872308460, marzelle@pharma-ethics.co.za, 9389_16320_4737.pdf, 231025961
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 07/03/2024 updating with UCT HREC initial approval True, University of Cape Town HREC, E 53 Room 46, Old Main Building, Groote Schuur Hospital, Observatory , Cape Town, 7925, South Africa, , 04 Mar 2024, +27214066492, hrec-enquiries@uct.ac.za, 9389_16444_4737.pdf, 807/2023
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 02/01/2024 Added budget total for this study MSD Pty Ltd, 117 - 16th Road, Halfway House, 1685, South Africa, Commercial Sector / Industry, , R, Primary Funder MSD Pty Ltd, 117 - 16th Road, Halfway House, 1685, South Africa, Commercial Sector / Industry, , R2198550.00, Primary Funder
Section Name Field Name Date Reason Old Value Updated Value
Sponsors Sponsors List 16/07/2024 Updated Sponsor Name Merck Sharp and Dohme LLC hereafter called the Sponsor or MSD, Private Bag 3, Halfway House, 1685, South Africa, Primary Sponsor, Commercial Sector/Industry, MSD Pty Ltd, 117 16th Road, Halfway House, 1685, South Africa, Primary Sponsor, Commercial Sector/Industry,
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 17/04/2025 Update with Therapeutic Area Head details Public Enquiries, Z, Nell, Ms., zoe.nell@merck.com, , +27116553000, 117 16th Road, Halfway House, 1685, South Africa, Snr Clinical Research Director Public Enquiries, U, Bridgmohun, Ms., urmilla.bridgmohun1@msd.com, , +27116553400, 117 16th Road, Halfway House, 1685, South Africa, Therapeutic Area Head
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 19/03/2024 Added PI after initial EC approval received. Principal Investigator, Y, Singh, Dr., Yashna.singh@hiv-research.org.za, , +27214066958, Main Road, Observatory, 7925, South Africa, Principal Investigator
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 02/01/2024 This statement is in alignment with WHO. IPD will not be provided to the public. IPD will be shared with Representatives from government agencies such as the South African Health Products Regulatory Authority (SAHPRA), the National Health Research Ethics Council (NHREC) and relevant Ethics Committees. IPD will not be provided to the public. IPD will be shared with representatives from government agencies such as the South Africa health Products Regulatory Authority (SAHPRA), the National Health Research Ethics Council (NHREC) and relevant Ethics Committees.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD-Sharing time frame 02/01/2024 Added time frame for release of study results. From study start until end of retention period as per MSD Policy period which is aligned with SA GCP From study start until end of retention period as MSD Policy period which is aligned with SA GCP. 6-months after study completion (180 days)