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.: PACTR202104874490818 Date of Registration: 16/04/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Cabotegravir And Rilpivirine: Efficacy and Safety Study (CARES)
Official scientific title A Phase 3b, Randomized, Multicenter, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-Acting Cabotegravir Plus Long-Acting Rilpivirine From Current Antiretroviral Regimen in HIV-1 Infected, Virologically Suppressed Adults in Sub-Saharan Africa
Brief summary describing the background and objectives of the trial Long-acting (LA) injectable therapy for the treatment of Human Immunodeficiency Virus (HIV)-1 infection offers a reduced dosing frequency and an additional option to the currently available two-drug oral combinations. A parenteral LA formulation of rilpivirine (RPV) for intramuscular (IM) injection in combination with ViiV Healthcare’s parenteral LA formulation of the integrase inhibitor cabotegravir (CAB) may offer a better tolerability and resistance profile, as well as improved adherence and treatment satisfaction in virologically suppressed patients. The combination regimen has been developed for maintenance of viral suppression (HIV-1 RNA <50 copies/mL) in HIV-1 infected individuals previously treated with standard-of-care antiretroviral therapy. Primary objective: To demonstrate the non-inferior antiviral activity of switching to IM RPV LA+CAB LA administered every 2 months compared with continuation of cART administered daily over 12 months in HIV-1 infected participants in a resource limited setting Secondary objectives: 1. To demonstrate the antiviral and immunologic activity of switching to IM RPV LA+CAB LA every 2 months compared to continuation of cART over 12 and 24 months of follow-up. 2. To evaluate the safety and tolerability of switching to RPV LA+CAB LA every 2 months compared to continuation of cART. 3. To assess viral resistance in participants experiencing protocol-defined confirmed virologic failure(plasma HIV-1 RNA ≥200 c/mL). 4. To assess the incidence of on-treatment genotypic resistance to CAB, RPV and other on-study cART up to Month 12and 24. 5. To evaluate adherence to treatment.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CARES
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 01/06/2021
Actual trial start date 15/09/2021
Anticipated date of last follow up 01/04/2024
Actual Last follow-up date 20/08/2024
Anticipated target sample size (number of participants) 512
Actual target sample size (number of participants) 512
Recruitment status Closed to recruitment,follow-up continuing
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
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 Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group cART Group A regimen of 2 NRTIs (tenofovir [TDF] plus either 3TC or FTC) plus an INI (DTG) or a NNRTI (EFV or NVP) single tablet or FDC regimen as per local country guidelines. Up to 24 months Participants will take a regimen of 2 NRTIs (tenofovir [TDF] plus either 3TC or FTC) plus an INI (DTG) or a NNRTI (EFV or NVP) single tablet or FDC regimen as per local country guidelines up to Month 24.Participants will be permitted to switch cART drugs in case of toxicity, or for treatment optimization and convenience; viral load must be tested and shown to be <1000 c/mL prior to elective treatment switch; there must be confirmed virologic rebound to ≥1000 c/mL prior to switch for treatment failure. 256 Active-Treatment of Control Group
Experimental Group RPV LA and CAB LA Group Up to 24 months The participants who opt for the OLI Phase will receive the study intervention in 2 phases: Oral Lead-in Phase: Starting on Day 1,participants will receive CAB 30 mg + RPV 25mg once daily for 4 weeks to be taken at approximately the same time each day with a meal. The purpose of the OLI Phase is to determine individual safety and tolerability of the combination prior to administration of RPV LA+CAB LA. Maintenance Phase: After the 4-week OLI Phase, participants will return for the Month 1 visit to take the last dose of oral RPV + CAB at the study-site, and receive the first IM RPVLA 900 mg+ CAB LA 600 mg initiation injections. The second initiation injections with RPV LA 900 mg + CAB LA 600 mg will be administered at Month 2, and then continuation injections will be administered every 2 months thereafter. Participants who opt for direct RPV LA+CAB LA injections (ie, without the OLI Phase) will remain on cART for 4 weeks after randomization, and will receive the first initiation injections of RPVLA+CAB LA at the Month 1 visit. The second initiation injections of RPVLA+CABLA will be administered at Month 2, followed by continuation injections of RPV LA+CAB LA every 2 months thereafter. 256
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Male or female 2. Aged ≥18 years. 3. On a stable ARV regimen(TDF plus either 3TC or FTC, plus an INI [DTG]or a NNRTI [EFV or NVP]per local country guidelines)for at least 6 months prior to screening. 4. Virologically suppressed with documented evidence of:  Viral load <50 c/mL at screening AND  Viral load <50 c/mL on a test preceding screening (within 4-12 months prior to screening) AND  No two consecutive viral load tests ≥50 c/mL in the 12 months prior to screening 5. No prior history o f virologic failure (defined as a confirmed plasma HIV-1 RNA measurement >200c/mL) at any time. 6. Must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. 7. A female participant is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin [hCG] urine test at screening and a negative urine hCG test at randomization) and not lactating. 8. A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak. 9. Male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study intervention. 10. Participants with asymptomatic chronic hepatitis C virus (HCV) infection will be allowed entry if liver enzymes meet entry criteria, have undergone appropriate work-up, and are not in an advanced, unstable liver disease stage. 11. Is willing and able to adhere to the lifestyle restrictions specified in this protocol. 1. Is currently participating in any other interventional study. 2. Is pregnant, breastfeeding or intends to become pregnant or breastfeed during the study, within the next 1 year. 3. Has evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease, except cutaneous Kaposi’s sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells/mm3 4. Has active TB co-infection and requires anti-TB treatment. 5. Has severe hepatic impairment, history of liver cirrhosis with or without hepatitis viral co-infection. 6. Has preexisting physical or mental condition (including substance abuse disorder and suicide risk) which, in the opinion of the Investigator, may interfere with the participant’s ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant. 7. Has had more than one seizure within one year (defined as within 365 days) prior to entry, or unstable or poorly controlled seizure disorder, as determined by the investigator or designee, based on available medical records. 8. Has a tattoo or other dermatological condition overlying the gluteus region. 9. Is positive for HBsAg or anti-HBc at screening. 10. Has ongoing or clinically significant medical conditions that in the opinion of the investigator may interfere with the absorption, distribution, metabolism or excretion of the study interventions or could affect participant safety. 11. Has a history o f coagulopathies, or current or anticipated need for chronic anticoagulationexcept forlow dose acetylsalicylic acid (daily dose ≤325mg). 12. Has known major INI or NNRTI resistance-associated mutation as defined in the International Antiviral Society-USA 2019 list, except for K103N, based on any historical resistance test result. 13. Has any verified Grade 4 laboratory abnormality. *More exclusion criteria in the study protocol. 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) 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 02/12/2020 Joint Clinical Research Centre REC Office
Ethics Committee Address
Street address City Postal code Country
Plot 101 Lubowa, off Entebbe Road Kampala 10005 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 24/02/2021 Uganda National Council for Science and Technology
Ethics Committee Address
Street address City Postal code Country
Plot 6 Kimera Road 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 15/04/2021 Moi Teaching and Referral Hospital Institutional Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
2nd floor. Door No. 219, Eldoret 254 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 02/06/2020 The Aga Khan University Institutional Scientific and Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
3rd Parklands Avenue, off Limuru Road Nairobi 254 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 14/07/2021 KENYA MEDICAL RESEARCH INSTITUTE SCIENTIFIC AND ETHICS REVIEW UNIT.
Ethics Committee Address
Street address City Postal code Country
Hospital Road, P.O. Box 1357 Kericho, Kenya Kericho 254 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 26/03/2021 University of Witwatersrand Johannesburg Human Research ethics committee
Ethics Committee Address
Street address City Postal code Country
Suite 189, Private bag x2600 Johannesburg 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 28/04/2021 South African Medical Research Council Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Francie Van Zijl Drive ,Parowvallei 7505 Capetown Capetown 7505 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Plasma HIV-1 RNA <50 c/mL At Month 12
Secondary Outcome Confirmed virologic failure (2 consecutive plasma HIV-1 RNA levels ≥200c/mL) At Month 12 and Month 24
Secondary Outcome Virological non-response (plasma HIV-1 RNA ≥50 c/mL) At Month 12 and Month 24
Secondary Outcome Plasma HIV-1 RNA <50 c/mL At Month 24
Secondary Outcome Change from baseline in CD4+ lymphocyte count At Month 12 and Month 24
Secondary Outcome Incident disease progression (HIV-associated conditions, AIDS and death) Through 12 and 24 months
Secondary Outcome Incident Grade 3 and Grade 4 AEs Through Month 12 and Month 24
Secondary Outcome Adverse events leading to treatment discontinuation Through Month 12 and Month 24
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Joint Clinical Research Centre Lubowa Hill, Plot 101 Entebbe Road Kampala 10005 Uganda
Joint Clinical Research Centre Fort Portal Kamwenge road Fort Portal Uganda
The Infectious Disease Institute McKinnell Knowledge Centre University Road Kampala 22418 Uganda
AMPATH Kenya Nandi Road Kapsoya Ainabkoi Eldoret 4606 Kenya
United States Army Medical Research Directorate Kenya K N H, Mbagathi Road Nairobi 1357 Kenya
Aga Khan University Hospital 3rd Parklands Avenue Nairobi Kenya
University of the Witwatersrand 1 Jan Smuts Ave, Braamfontein Johannesburg 2001 South Africa
South African Medical Research Council Francie Van Zijl Dr, Parow Valley Cape Town 4091 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Janssen Pharmaceutica NV Turnhoutseweg 30, B-2340 Beerse Belgium
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Joint Clinical Research Centre Limited Plot 101, Lubowa State, off Entebbe Road Kampala Uganda Medical Research Institution
COLLABORATORS
Name Street address City Postal code Country
Joint Clinical Research Centre Fort Portal Kamwenge Road Fort Portal Uganda
The Infectious Disease Institute McKinnell Knowledge Centre University Road Kampala Uganda
AMPATH Kenya Nandi Road Kapsoya Ainabkoi Eldoret 30100 Kenya
United States Army Medical Research Directorate Kenya Kenya Medical Research Institute, K N H, Mbagathi Road Kericho Kenya
Aga Khan University Hospital 3rd Parklands Avenue Nairobi Kenya
University of the Witwatersrand 1 Jan Smuts Ave, Braamfontein Johannesburg South Africa
South African Medical Research Council Francie Van Zijl Dr, Parow Valley Cape Town South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Cissy Kityo ckityo@jcrc.org.ug +256752769168 Plot 101 Lubowa State, Off Entebbe Road
City Postal code Country Position/Affiliation
Kampala Uganda Executive Director
Role Name Email Phone Street address
Public Enquiries Ivan Mambule imambule@jcrc.org.ug +256772594411 Plot 101 Lubowa State, Off Entebbe Road
City Postal code Country Position/Affiliation
Kampala Uganda Project Lead
Role Name Email Phone Street address
Scientific Enquiries Nicholas Paton nick_paton@nuhs.edu.sg +6567795555 NUHS Tower Block Level 10, 1E Kent Ridge Road
City Postal code Country Position/Affiliation
Singapore 119228 Singapore Scientific Lead
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All of the individual participant data collected during the trial, after deidentification will be shared. Study Protocol Beginning 12 months and ending 36 months following article publication. Investigators who provide a methodologically sound proposal that has been reviewed and approved by the Trial Steering Committee. Proposals for access should be directed to the study Chief Investigator.
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 - 22/04/2025
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information