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.: PACTR202404870570433 Date of Approval: 02/04/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title B/F/TAF to DTG/3TC Switch Study
Official scientific title Efficacy, Safety and Tolerability of Switching to DTG/3TC Single Tablet Regimen from B/F/TAF in Older Persons Living with HIV in Kenya
Brief summary describing the background and objectives of the trial Background Three drug regimens for the treatment of HIV are widely used and successful in achieving viral suppression. However, they are associated with various adverse events including renal and bone disease, anemia, mitochondrial toxicity, and possible association with increased cardiovascular events. Data from the ongoing BFTAF Elderly Switch Study has demonstrated high rates of renal insufficiency and osteoporosis in people living with HIV aged 60 years or more, hence the need for safe treatment options. Two drug regimens (2DR) have demonstrated non-inferiority to three drug regimens in patients who are treatment naïve as well as in those who are virally suppressed on a first-line regimen and potentially have lower toxicity, fewer adverse drug events and a lower drug burden. Objectives To assess the efficacy and safety of switch to dolutegravir and lamivudine (DTG/3TC) single tablet regimen from bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in persons living with HIV aged 60 years old or older.
Type of trial Non-Randomised
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 06/05/2024
Actual trial start date
Anticipated date of last follow up 31/07/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 240
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
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
Single Group Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Switch to 2DR Single combined pill containing 50mg of DTG and 300mg of 3TC administered orally once a day 96 weeks On the day of enrollment, eligible participants will be switched to a fixed-dose combination of DTG/3TC (50mg/300mg) daily for a follow-up period of 96 weeks 240
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Able and willing to understand and comply with the protocol requirements, instructions and restrictions 2. Able and willing to give informed consent 3. Have been randomised to the B/F/TAF arm and completed the B/F/TAF-elderly study. Participant should be on B/F/TAF until day 1 of entry into the current study 4. HIV-1 RNA viral load < 50 copies/ml at screening (within 28 days prior to enrollment) 1. Confirmed treatment failure as defined by two consecutive HIV-1 RNA viral loads ≥ 50 copies/ml separated by at least 2 weeks, after at least 6 months on ART or after a documented HIV-1 RNA viral load < 50 copies/ml 2. Using any protocol-defined prohibited medicine where the participant is unwilling or unable to switch to an alternative 3. Evidence of hepatitis B virus (HBV) infection based on the results of testing at screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs) and HBV DNA 4. Has AST and/or ALT at least 5-times greater than the upper limit of normal 5. Severe hepatic impairment (Class C) as determined by Child-Pugh classification 6. Has a CrCl below 30 ml/min (as estimated using the Cockcroft-Gault estimate for glomerular filtration rate) 7. Documented opportunistic infection within 4 weeks prior to the study enrolment 8. Any condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator’s opinion, interfere with assessments or completion of the study 9. Untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Participants who are at least 7 days post completed treatment are eligible. 10. History or presence of allergy or intolerance to the study treatment or their components or drugs of their class or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. 11. Ongoing malignancy other than cutaneous Kaposi’s sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia. 12. Participants who in the investigator’s judgment, poses a significant suicidality risk 13. Any evidence of any major 3TC resistance associated mutations (M184V/I and/or K65R and/or MDR) or presence of any major INSTI resistance associated mutation 80 and over: 80+ Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 60 Year(s) 100 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 15/03/2024 Jaramogi Oginga Odinga Teaching and Referral Hospital Institutional Scientific and Ethical Review Committee
Ethics Committee Address
Street address City Postal code Country
Kisumu-Kakamega Highway, Kibuye Kisumu 40100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Participants with plasma HIV-1 RNA ≥ 50 copies/mL (Snapshot algorithm) at Week 48 Week 48
Secondary Outcome Participants with plasma HIV-1 RNA ≥ 50 copies/mL (Snapshot algorithm) at 24 and 96 weeks Weeks 24 and 96
Secondary Outcome Participants with plasma HIV-1 RNA <50 copies/mL (Snapshot algorithm) at 24, 48 and 96 weeks Weeks 24, 48 and 96
Secondary Outcome Absolute values and changes from baseline in CD4+ cells count and CD4:CD8 ratio at 24, 48 and 96 weeks Weeks 24, 48 and 96
Secondary Outcome Occurrence of disease progression (HIV associated conditions, AIDS, and death) through Weeks 24, 48 and 96. Weeks 24, 48 and 96
Secondary Outcome Change in lipid parameters (total cholesterol, HDL and LDL cholesterol, triglyceride and TC/HDL ratio) from baseline to weeks 24, 48 and 96 Weeks 24, 48 and 96
Secondary Outcome Change in fasting blood sugar from baseline to weeks 48 and 96 Weeks 48 and 96
Secondary Outcome Change in blood pressure over 24, 48 and 96 weeks Weeks 24, 48 and 96
Secondary Outcome Mean change in weight at week 24, 48 and 96 Weeks 24, 48 and 96
Secondary Outcome Change from baseline in total and regional (trunk and limbs) fat and lean (fat-free) mass by DXA at 96 weeks in a subset of participants performing DXA scans Week 96
Secondary Outcome Proportion of participants with ≥ 10% weight gain at weeks 48 and 96 Weeks 48 and 96
Secondary Outcome Change from baseline in ASCVD score at weeks 48 and 96 Weeks 48 and 96
Secondary Outcome Patient satisfaction (HIVTSQs) at baseline, weeks 24 and 96 Weeks 24 and 96
Secondary Outcome Patient satisfaction (HIVTSQc) at week 48 Week 48
Secondary Outcome To evaluate health related quality of life (WHOQOL HIV) at baseline, week 48 and week 96 Weeks 48 and 96
Secondary Outcome To assess the occurrence of viral resistance in participants meeting confirmed virologic withdrawal criterion (Plasma HIV-1 RNA ≥ 200 copies/mL preceded by a Plasma HIV-1 RNA ≥ 50 copies/mL) over time Weeks 24, 48 and 96
Secondary Outcome To investigate the incidence and severity of AEs and laboratory abnormalities over time through Week 96 Weeks 24, 48 and 96
Secondary Outcome To investigate the occurrence of DTG/3TC-non-Serious Adverse drug-related reactions, all SAEs and proportion of participants who discontinue treatment due to adverse event Weeks 24, 48 and 96
Secondary Outcome To assess the change from Baseline (Day 1) in renal biomarkers at Weeks 48 and 96 Weeks 48 and 96
Secondary Outcome To assess changes from baseline in estimated glomerular filtration rate (Creatinine and Cystatin-C, CKD-EPI, and urinary protein/creatinine at 48 and 96 weeks Weeks 48 and 96
Secondary Outcome To assess the change from baseline in AST, ALT and GGT levels at week 48 and 96 Weeks 48 and 96
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenyatta National Hospital Hospital Road, Upperhill Nairobi 00202 Kenya
Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu-Kakamega Highway, Kibuye Kisumu 40100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Mylan Laboratories 564/A/22, Road No. 92, Jubilee Hills Hyderabad 500 096 India
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Nairobi University Way Nairobi 00100 Kenya University
COLLABORATORS
Name Street address City Postal code Country
Loice Achieng Ombajo Faculty of Health Sciences, University of Nairobi Nairobi 00202 Kenya
Jeremy Penner Faculty of Health Sciences, University of Nairobi Nairobi 00202 Kenya
Anton Pozniak Chelsea and Westminster Hospital NHS Foundation London United Kingdom
Sanjay Bhagani Royal Free London NHS Foundation Trust London United Kingdom
Simon Wahome Kenyatta National Hospital Nairobi Kenya
Rose Wafula National AIDS and STIs Control Program, Kenya Nairobi Kenya
Florentius Ndinya Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu Kenya
Eve Koile Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu Kenya
Rukia Aksam Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu Kenya
Phoebe Juma Faculty of Health Sciences, University of Nairobi Nairobi Kenya
Joseph Nkuranga Faculty of Health Sciences, University of Nairobi Nairobi Kenya
Michelle Ogolla Kisare ViiV Healthcare Nairobi Kenya
Samuel Nguku Gitau Aga Khan University Hospital Nairobi Kenya
Caroline Nasambu Wafula Jaramogi Oginga Odinga Teaching and Referral Hospital Kisumu Kenya
Diana Kemunto Nyakoe Mbagathi Hospital Nairobi Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Loice Achieng Ombajo loisea@uonbi.ac.ke +254722576984 Faculty of Health Sciences, University of Nairobi
City Postal code Country Position/Affiliation
Nairobi 00202 Kenya Principal Investigator
Role Name Email Phone Street address
Public Enquiries Joseph Nkuranga dnkuranga@uonbi.ac.ke +254737223988 Faculty of Health Sciences, University of Nairobi
City Postal code Country Position/Affiliation
Nairobi 00202 Kenya Study Coordinator
Role Name Email Phone Street address
Scientific Enquiries Jeremy Penner pennerjak@gmail.com +254732391001 Faculty of Health Sciences, University of Nairobi
City Postal code Country Position/Affiliation
Nairobi 00202 Kenya Co Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Participant data that was used to generate the final manuscript from the study. The data will be de-identified and a data dictionary provided alongside the raw data. Analytic Code,Statistical Analysis Plan,Study Protocol Immediately after the publication of the final manuscript and for 24 months thereafter Access to IPD will be subject to the University of Nairobi data sharing requirements. Written requests should be submitted to the Principal Investigator providing a brief description of the individual or group making the request and detailing the reason for the same. Prior to sharing of the data, the requestor will be required to sign a data access and sharing agreement.
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