A Study to Evaluate Efficacy and Safety of Cabotegravir (CAB) Long Acting (LA) Plus (+) Rilpivirine (RPV) LA Versus BIKTARVY® (BIK) in Participants With Human Immunodeficiency Virus (HIV)-1 Who Are Virologically Suppressed (SOLAR)

• ClinicalTrials.gov Identifier: NCT04542070
• Recruitment Status: Completed
• First Posted: September 9, 2020
• Results First Posted: September 13, 2023
• Last Update Posted: September 13, 2023
• Sponsor: ViiV Healthcare
• Collaborator: Janssen, LP
• Information provided by (Responsible Party): ViiV Healthcare

Tracking Information

• First Submitted Date: September 1, 2020
• First Posted Date: September 9, 2020
• Results First Submitted Date: July 12, 2023
• Results First Posted Date: September 13, 2023
• Last Update Posted Date: September 13, 2023
• Actual Study Start Date: November 9, 2020
• Actual Primary Completion Date: July 13, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 12, 2023)

• Percentage of Participants With Plasma Human Immunodeficiency Viruses (HIV)-1 Ribonucleic Acid (RNA) Greater Than or Equal to (>=) 50 Copies Per Milliliter (c/mL) at Month 12/11 - ITT-E Population [ Time Frame: At month 12/11 ]
  Percentage of participants with plasma HIV 1 RNA >= 50 c/mL at month 12 was assessed using the food and drug administration (FDA) snapshot algorithm. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL), along with study drug discontinuation status. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
• Percentage of Participants With Plasma HIV-1 RNA Greater >=50 Copies Per Milliliter (c/mL) at Month 12/11 - mITT-E Population [ Time Frame: At month 12/11 ]
  Percentage of participants with plasma HIV 1 RNA >= 50 c/mL at month 12 was assessed using the food and drug administration (FDA) snapshot algorithm. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL), along with study drug discontinuation status. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

Original Primary Outcome Measures (submitted: September 1, 2020)

• Percentage of participants with plasma human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) greater than or equal to (>=) 50 copies per mL (c/mL) - OLI [ Time Frame: At Month 12 ]
  Participants with plasma HIV-1 RNA >=50 c/mL per Food and Drug Administration (FDA) snapshot algorithm will be assessed.
• Percentage of participants with plasma HIV-1 RNA >=50 c/mL - D2I [ Time Frame: At Month 11 ]
  Participants with plasma HIV-1 RNA >=50 c/mL per FDA snapshot algorithm will be assessed.
• Percentage of participants with plasma HIV-1 RNA >=50 c/mL - BIK [ Time Frame: At Month 12 ]
  Participants with plasma HIV-1 RNA >=50 c/mL per FDA snapshot algorithm will be assessed.

Current Secondary Outcome Measures (submitted: August 23, 2023)

• Percentage of Participants With Plasma HIV-1 RNA Less Than (<)50 c/mL at Month 12/11 - ITT-E Population [ Time Frame: At month 12/11 ]
  Percentage of participants with plasma HIV 1 RNA < 50 c/mL was assessed using the FDA snapshot algorithm. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL), along with study drug discontinuation status. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
• Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Month 12/11 -mITT-E Population [ Time Frame: At month 12/11 ]
  Percentage of participants with plasma HIV 1 RNA < 50 c/mL was assessed using the FDA snapshot algorithm. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL), along with study drug discontinuation status. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
• Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Month 6/5 - ITT-E Population [ Time Frame: At month 6/5 ]
  Percentage of participants with plasma HIV 1 RNA < 50 c/mL was assessed using the FDA snapshot algorithm. For the Q2M arm, data from the Q2M OLI participants at Month 6 visit and Q2M D2I participants at Month 5 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL), along with study drug discontinuation status. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
• Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Month 6/5 - mITT-E Population [ Time Frame: At month 6/5 ]
  Percentage of participants with plasma HIV 1 RNA < 50 c/mL was assessed using the FDA snapshot algorithm. For the Q2M arm, data from the Q2M OLI participants at Month 6 visit and Q2M D2I participants at Month 5 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL), along with study drug discontinuation status. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
• Number of Participants With Protocol-defined Confirmed Virologic Failure (CVF) Through Month 6/5 and 12/11 [ Time Frame: Up to month 12 ]
  Protocol-defined confirmed virologic failure was defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >= 200 c/mL (Day 1 values are not applicable) after prior suppression to <200 c/mL. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at Month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. Cumulative number of participants with protocol defined CVF through Month 6/5 and 12/11 has been presented.
• Percentage of Participants With Plasma HIV-1 RNA Greater Than or Equal to (>=) 50 c/mL at Month 6/5 [ Time Frame: At month 6/5 ]
  Percentage of participants with plasma HIV 1 RNA >= 50 c/mL at month 6 was assessed using the food and drug administration (FDA) snapshot algorithm. For the Q2M arm, data from the Q2M OLI participants at Month 6 visit and Q2M D2I participants at Month 5 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL), along with study drug discontinuation status. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
• Absolute Values of HIV Viral Load [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log10) values for plasma HIV-1 RNA has been presented. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in HIV Viral Load [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Logarithm to base 10 values for plasma HIV-1 RNA has been presented. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Absolute Values of Cluster of Differentiation 4 Plus (CD4+) Cell Count [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Blood samples were collected and CD4+ cell count was assessed using flow cytometry. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in CD4+ Cell Count [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Blood samples were collected and CD4+ cell count was assessed using flow cytometry. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Number of Participants With Treatment-emergent Phenotypic Resistance Through Month 12/11 [ Time Frame: Up to Month 12/11 ]
  Blood samples were collected to evaluate the phenotypic resistance to CAB, RPV, BIC, FTC, and TAF. For each participant, prevalence of phenotype, fold changes to CAB, RPV, and BIC, replication capacity of Integrase, protease, and reverse transcriptase enzymes at the time of CVF was assessed. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. No participants in the BIK arm met CVF.
• Number of Participants With Treatment-emergent Phenotypic Resistance Through Month 6/5 [ Time Frame: Up to Month 6/5 ]
  Blood samples were collected to evaluate the phenotypic resistance to CAB, RPV, BIC, FTC, and TAF. For each participant, prevalence of phenotype, fold changes to CAB, RPV, and BIC, replication capacity of Integrase, protease, and reverse transcriptase enzymes at the time of CVF was assessed. For the Q2M arm, data from the Q2M OLI participants at Month 6 visit and Q2M D2I participants at Month 5 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. No participants in the BIK arm met CVF.
• Number of Participants With Treatment-emergent Genotypic Resistance Through Month 12/11 [ Time Frame: Up to Month 12/11 ]
  Blood samples were collected to evaluate the genotypic resistance to CAB, RPV, BIC, FTC, and TAF. For each participant, prevalence of resistance mutations and genotypic susceptibility at the time of CVF was assessed. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. No participants in the BIK arm met CVF.
• Number of Participants With Treatment-emergent Genotypic Resistance Through Month 6/5 [ Time Frame: Up to Month 6/5 ]
  Blood samples were collected to evaluate the genotypic resistance to CAB, RPV, BIC, FTC, and TAF. For each participant, prevalence of resistance mutations and genotypic susceptibility at the time of CVF was assessed. For the Q2M arm, data from the Q2M OLI participants at Month 6 visit and Q2M D2I participants at Month 5 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. No participants in the BIK arm met CVF.
• Change From Baseline in Bone Biomarkers: Specific Alkaline Phosphatase, Procollagen Type 1 N-Terminal Propeptide, Type 1 Collagen Cross-linked C-telopeptide, Osteocalcin (Micrograms Per Liter (ug/L)) [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Serum samples were collected to evaluate bone specific biomarkers: specific alkaline phosphatase, procollagen type 1 N-propeptide, type 1 collagen cross-linked C-telopeptide, osteocalcin. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in Bone Biomarkers: Serum 25-hydroxyvitamin D (Nanomoles Per Liter (Nmol/L)) [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Serum samples were collected to evaluate bone specific biomarkers: serum 25-hydroxyvitamin D. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in Renal Biomarkers: Specific Serum Beta-2 Microglobulin, Cystatin c, Retinol Binding Protein, Urine Beta-2 Microglobulin (Milligrams Per Liter [mg/L]) [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Serum samples were collected to evaluate renal specific biomarkers: specific serum beta-2 microglobulin, cystatin c, retinol binding protein, urine beta-2 microglobulin. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in Renal Biomarkers: Urine Phosphate (Millimoles Per Liter (mmol/L)) [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Serum samples were collected to evaluate renal specific biomarkers: urine phosphate. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in Renal Biomarker: Urine Retinol Binding Protein 4 (Microgram Per Liter (ug/L)) [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Serum samples were collected to evaluate renal specific biomarkers: urine retinol binding protein 4. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in Renal Biomarker: Urine Retinol Binding Protein/Creatinine (Milligram Per Mole (mg/Mol)) [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Serum samples were collected to evaluate renal specific biomarkers: urine retinol binding protein/creatinine. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in Renal Biomarker: Urine Beta-2 Microglobulin/ Creatinine (Grams Per Mole (g/Mol)) [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  Serum samples were collected to evaluate renal specific biomarkers: urine beta-2 microglobulin/ creatinine. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in Percentage of Participants With Metabolic Syndrome at Month 12/11 [ Time Frame: Baseline (Day 1) and at Month 12/11 ]
  Metabolic syndrome defined as cluster of conditions that occurred together increasing one's risk of heart disease, stroke and type 2 diabetes mellitus (DM). These conditions included increased blood pressure (BP), elevated blood glucose levels, excess body fat around the waist and abnormal fasting cholesterol and triglyceride (TG) levels. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in Percentage of Participants With Metabolic Syndrome at Month 6/5 [ Time Frame: Baseline (Day 1) and at month 6/5 ]
  Metabolic syndrome defined as cluster of conditions that occurred together increasing one's risk of heart disease, stroke and type 2 diabetes mellitus (DM). These conditions included increased blood pressure (BP), elevated blood glucose levels, excess body fat around the waist and abnormal fasting cholesterol and triglyceride (TG) levels. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 visit and Q2M D2I participants at Month 5 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit.
• Change From Baseline in Homeostasis Model of Assessment-insulin Resistance (HOMA-IR) [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance. HOMA-IR is calculated as fasting insulin microunits per liter (microU/L) multiplied by fasting glucose (nmol/L) divided by 22.5. Higher HOMA-IR values indicate increased insulin resistance; values <2 is generally regarded as normal. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Percentage of Participants With Treatment Preference as Assessed Using Preference Questionnaire at Month 12/11 - Q2M [ Time Frame: Up to month 12/11 ]
  Participants who had switched from the daily oral BIK regimen to CAB + RPV, were assessed as per the preference questionnaire every two months. There were 3 preference questions included to assess the preferred treatment 1) Long-acting injectable HIV medication, 2) Daily oral HIV medication, 3) No Preference. This endpoint was only planned to be analyzed for Q2M arm only. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. Data represented included maintenance withdrawal or Month 12/11.
• Change From Baseline in Total Treatment Satisfaction Score Using HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  The HIVTSQs total treatment satisfaction score comprised of 11 items based on HIVTSQ questionnaire each graded on a scale of 0 (very dissatisfied) to 6 (very satisfied) which were summed to produce a total score range of 0-66. Higher scores represent greater treatment satisfaction. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Baseline in Individual Item Scores Using HIVTSQs [ Time Frame: Baseline (Day 1) and up to Month 12 ]
  The individual item scores on HIVTSQs scale were rated on a scale of 6 (very satisfied, convenient, flexible, etc.) to -6 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater satisfaction with each aspect of treatment. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from baseline is defined as post-dose visit value minus baseline value. For the Q2M arm, data from the Q2M OLI participants at Month 6 and 12 visit and Q2M D2I participants at Month 5 and 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 6 and 12 visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• HIV Treatment Satisfaction Change Questionnaire (HIVTSQc) Total Score at Month 12/11 [ Time Frame: At Month 12/11 ]
  HIV treatment satisfaction change questionnaire (HIVTSQc) total Score is computed with items 1-11 which were summed to produce a total score range of -33 to 33. Higher score indicated greater improvement in the satisfaction with the treatment and lower score indicated greater deterioration in treatment satisfaction. A score of 0 represents no change. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Individual Item Scores of HIVTSQc at Month 12/11 [ Time Frame: At Month 12/11 ]
  Individual item scores were rated on a scale of +3 (much more satisfied', 'much more convenient', 'much more flexible') to -3 (much less satisfied', 'much less convenient', 'much less flexible'). Higher score indicates greater improvement, and lower score indicates greater deterioration in satisfaction with each aspect of treatment. A score of 0 represents no change. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Month 2/1 in Dimension Scores Using Perception of Injection (PIN) Questionnaire - Q2M [ Time Frame: From Month 2/1 up to Month 12 ]
  The PIN questionnaire was used to explore the dimension scores based on 4 dimensions including acceptance of injection site reactions (ISRs), Bother from ISRs, Leg movement and Sleep categories. Domain scores were calculated as a mean of all items with the domain. The PIN response options range from 1 (totally acceptable) to 5 (not at all acceptable). This endpoint was only planned to be analyzed for Q2M arm. Month 2/1 refers to the Month 2 (OLI and BIK) visit/Month 1 (DTI) visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.
• Change From Month 2/1 in Individual Item Scores Using PIN Questionnaire- Q2M [ Time Frame: From Month 2/1 up to Month 12 ]
  The PIN questionnaire was used to explore the individual item scores based on anxiety before, pain, satisfaction, anxiety after and willingness categories. The items in the scale are rated on a 5-point scale and questions are phrased in such a way as to ensure that 1 is very dissatisfied and 5 was very satisfied. This endpoint was only planned to be analyzed for Q2M arm. Month 2/1 refers to the Month 2 (OLI and BIK) visit/Month 1 (DTI) visit. Month 6/5 refers to the Month 6 (OLI and BIK) visit/Month 5 (DTI) visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit.

Original Secondary Outcome Measures (submitted: September 1, 2020)

• Percentage of participants with plasma HIV-1 RNA less than (<)50 c/mL - OLI [ Time Frame: At Months 6 and 12 ]
  Participants with plasma HIV-1 RNA <50 c/mL per FDA snapshot algorithm will be assessed.
• Percentage of participants with plasma HIV-1 RNA <50 c/mL - D2I [ Time Frame: At Months 5 and 11 ]
  Participants with plasma HIV-1 RNA <50 c/mL per FDA snapshot algorithm will be assessed.
• Percentage of participants with plasma HIV-1 RNA <50 c/mL - BIK [ Time Frame: At Months 6 and 12 ]
  Participants with plasma HIV-1 RNA <50 c/mL per FDA snapshot algorithm will be assessed.
• Percentage of participants with protocol-defined confirmed virologic failure (CVF) - OLI [ Time Frame: Up to Month 12 ]
  CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL.
• Percentage of participants with protocol-defined CVF - D2I [ Time Frame: Up to Month 11 ]
  CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL.
• Percentage of participants with protocol-defined CVF - BIK [ Time Frame: Up to Month 12 ]
  CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL.
• Percentage of participants with HIV-RNA >= 50 c/mL - OLI [ Time Frame: At Month 6 ]
  Participants with plasma HIV-1 RNA >=50 c/mL will be assessed per FDA snapshot algorithm.
• Percentage of participants with HIV-RNA >= 50 c/mL - D2I [ Time Frame: At Month 5 ]
  Participants with plasma HIV-1 RNA >=50 c/mL will be assessed per FDA snapshot algorithm.
• Percentage of participants with HIV-RNA >= 50 c/mL - BIK [ Time Frame: At Month 6 ]
  Participants with plasma HIV-1 RNA >=50 c/mL will be assessed per FDA snapshot algorithm.
• Absolute values of HIV viral load - OLI [ Time Frame: At Months 6 and 12 ]
  Absolute values of HIV viral load will be assessed.
• Absolute values of HIV viral load - D2I [ Time Frame: At Months 5 and 11 ]
  Absolute values of HIV viral load will be assessed.
• Absolute values of HIV viral load - BIK [ Time Frame: At Months 6 and 12 ]
  Absolute values of HIV viral load will be assessed.
• Change from Baseline in HIV viral load (c/mL) - OLI [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
  Change from Baseline in HIV viral load will be assessed.
• Change from Baseline in HIV viral load (c/mL) - D2I [ Time Frame: Baseline (Day 1) and at Months 5 and 11 ]
  Change from Baseline in HIV viral load will be assessed.
• Change from Baseline in HIV viral load (c/mL) - BIK [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
  Change from Baseline in HIV viral load will be assessed.
• Absolute values of cluster of differentiation 4 plus (CD4+) cell counts - OLI [ Time Frame: At Months 6 and 12 ]
  Absolute values of CD4+ cell counts will be assessed.
• Absolute values of CD4+ cell counts - D2I [ Time Frame: At Months 5 and 11 ]
  Absolute values of CD4+ cell counts will be assessed.
• Absolute values of CD4+ cell counts - BIK [ Time Frame: At Months 6 and 12 ]
  Absolute values of CD4+ cell counts will be assessed.
• Change from Baseline in CD4+ cell counts (Cells per cubic millimeters [cells/mm^3]) - OLI [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
  Change from Baseline in CD4+ cell will be assessed.
• Change from Baseline in CD4+ cell counts (cells/mm^3) - D2I [ Time Frame: Baseline (Day 1) and at Months 5 and 11 ]
  Change from Baseline in CD4+ cell will be assessed.
• Change from Baseline in CD4+ cell counts (cells/mm^3) - BIK [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
  Change from Baseline in CD4+ cell will be assessed.
• Number of participants with treatment-emergent phenotypic resistance - OLI [ Time Frame: Up to Month 12 ]
  Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent phenotypic resistance to CAB, RPV, BIC, FTC, and TAF.
• Number of participants with treatment-emergent phenotypic resistance - D2I [ Time Frame: Up to Month 11 ]
  Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent phenotypic resistance to CAB, RPV, BIC, FTC, and TAF.
• Number of participants with treatment-emergent phenotypic resistance - BIK [ Time Frame: Up to Month 12 ]
  Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent phenotypic resistance to CAB, RPV, BIC, FTC, and TAF.
• Number of participants with treatment-emergent genotypic resistance - OLI [ Time Frame: Up to Month 12 ]
  Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent genotypic resistance to CAB, RPV, BIC, FTC, and TAF.
• Number of participants with treatment-emergent genotypic resistance - D2I [ Time Frame: Up to Month 11 ]
  Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent genotypic resistance to CAB, RPV, BIC, FTC, and TAF.
• Number of participants with treatment-emergent genotypic resistance - BIK [ Time Frame: Up to Month 12 ]
  Plasma samples will be collected from participants experiencing protocol-defined CVF for assessing treatment-emergent genotypic resistance to CAB, RPV, BIC, FTC, and TAF.
• Number of participants with abnormal renal and bone biomarkers - OLI [ Time Frame: At Months 6 and 12 ]
  Blood and urine samples will be collected over time to assess renal and bone biomarkers.
• Number of participants with abnormal renal and bone biomarkers - D2I [ Time Frame: At Months 5 and 11 ]
  Blood and urine samples will be collected over time to assess renal and bone biomarkers.
• Number of participants with abnormal renal and bone biomarkers - BIK [ Time Frame: At Months 6 and 12 ]
  Blood and urine samples will be collected over time to assess renal and bone biomarkers.
• Percentage of participants with Metabolic syndrome - OLI [ Time Frame: At Months 6 and 12 ]
  Metabolic syndrome is a cluster of conditions that occurs together increasing one's risk of heart disease, stroke and type 2 diabetes mellitus (DM). These conditions include increased blood pressure (BP), elevated blood glucose levels, excess body fat around the waist and abnormal fasting cholesterol and triglyceride (TG) levels.
• Percentage of participants with Metabolic syndrome - D2I [ Time Frame: At Months 5 and 11 ]
  Metabolic syndrome is a cluster of conditions that occurs together increasing one's risk of heart disease, stroke and type 2 DM. These conditions include increased BP, elevated blood glucose levels, excess body fat around the waist and abnormal fasting cholesterol and TG levels.
• Percentage of participants with Metabolic syndrome - BIK [ Time Frame: At Months 6 and 12 ]
  Metabolic syndrome is a cluster of conditions that occurs together increasing one's risk of heart disease, stroke and type 2 DM. These conditions include increased BP, elevated blood glucose levels, excess body fat around the waist and abnormal fasting cholesterol and TG levels.
• Number of participants with insulin resistance - OLI [ Time Frame: At Months 6 and 12 ]
  Insulin resistance will be assessed using homeostasis model of assessment-insulin resistance (HOMA-IR) Score.
• Number of participants with insulin resistance - D2I [ Time Frame: At Months 5 and 11 ]
  Insulin resistance will be assessed using HOMA-IR Score.
• Number of participants with insulin resistance -BIK [ Time Frame: At Months 6 and 12 ]
  Insulin resistance will be assessed using HOMA-IR Score.
• Percentage of participants with their treatment Preference as Assessed Using Preference Questionnaire - OLI [ Time Frame: At Month 12 ]
  The "Preference" questionnaire will include 3 questions and assess whether participants prefer the CAB LA + RPV LA injectable treatment or the daily oral ARV regimen, also evaluating the attributes supporting this preference.
• Percentage of participants with their Treatment Preference as Assessed Using Preference Questionnaire - D2I [ Time Frame: At Month 11 ]
  The "Preference" questionnaire will include 3 questions and assess whether participants prefer the CAB LA + RPV LA injectable treatment or the daily oral ARV regimen, also evaluating the attributes supporting this preference.
• Percentage of Participants with their treatment Preference as Assessed Using Preference Questionnaire - BIK [ Time Frame: At Month 12 ]
  The "Preference" questionnaire will include 3 questions and assess whether participants prefer the CAB LA + RPV LA injectable treatment or the daily oral ARV regimen, also evaluating the attributes supporting this preference.
• Change From Baseline in Total Treatment Satisfaction Score using HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) (scores on a scale) - OLI [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
  The HIVTSQs treatment satisfaction questionnaire comprises of 1-12 questions and the total treatment satisfaction score is computed with items 1-11 and summed to produce a score with a possible range of 0 to 66. Higher scores represent greater treatment satisfaction as compared to the past few weeks.
• Change From Baseline in Total Treatment Satisfaction Score using HIVTSQs (scores on a scale) - D2I [ Time Frame: Baseline (Day 1) and at Months 5 and 11 ]
  The HIVTSQs treatment satisfaction questionnaire comprises of 1-12 questions and the total treatment satisfaction score is computed with items 1-11 and summed to produce a score with a possible range of 0 to 66. Higher scores represent greater treatment satisfaction as compared to the past few weeks.
• Change From Baseline in Total Treatment Satisfaction Score using HIVTSQs (scores on a scale)- BIK [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
  The HIVTSQs treatment satisfaction questionnaire comprises of 1-12 questions and the total treatment satisfaction score is computed with items 1-11 and summed to produce a score with a possible range of 0 to 66. Higher scores represent greater treatment satisfaction as compared to the past few weeks.
• Change From Baseline in individual item scores using HIVTSQs (scores on a scale) - OLI [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
  HIVTSQs is a 12 item questionnaire. The individual item scores on HIVTSQs scale are rated as 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater satisfaction with each aspect of treatment.
• Change From Baseline in individual item scores using HIVTSQs (scores on a scale) - D2I [ Time Frame: Baseline (Day 1) and at Months 5 and 11 ]
  HIVTSQs is a 12 item questionnaire. The individual item scores on HIVTSQs scale are rated as 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater satisfaction with each aspect of treatment.
• Change From Baseline in individual item scores using HIVTSQs (scores on a scale) - BIK [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
  HIVTSQs is a 12 item questionnaire. The individual item scores on HIVTSQs scale are rated as 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater satisfaction with each aspect of treatment.
• Number of participants with change in treatment satisfaction over time using the HIV Treatment Satisfaction Change Questionnaire (HIVTSQc)- OLI [ Time Frame: At Month 12 ]
  The HIVTSQc is a 1-12 items questionnaire. Each item is scored -3 to 3. Total treatment satisfaction change score is computed using items 1 to 11 and are summed to produce a score with a possible range of -33 to 33. Higher the score, greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment. A score of 0 will represent no change.
• Number of participants with change in treatment satisfaction over time using HIVTSQc - D2I [ Time Frame: At Month 11 ]
  The HIVTSQc is a 1-12 items questionnaire. Each item is scored -3 to 3. Total treatment satisfaction change score is computed using items 1 to 11 and are summed to produce a score with a possible range of -33 to 33. Higher the score, greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment. A score of 0 will represent no change.
• Number of participants with change in treatment satisfaction over time using HIVTSQc - BIK [ Time Frame: At Month 12 ]
  The HIVTSQc is a 1-12 items questionnaire. Each item is scored -3 to 3. Total treatment satisfaction change score is computed using items 1 to 11 and are summed to produce a score with a possible range of -33 to 33. Higher the score, greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment. A score of 0 will represent no change.
• Number of participants with change in Dimension Scores Using Perception of Injection (PIN) Questionnaire - OLI [ Time Frame: At Months 2, 6, and 12 ]
  The PIN questionnaire explores the bother of pain at the injection site and injection site reaction (ISRs), anxiety before and after injection, willingness to receive an HIV injectable treatment the following visit and satisfaction with the mode of treatment administration of individuals receiving injection and perceptions of individuals associated with receiving injections. This measure contains 21 items that measure pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside of a clinical trial. The items in the scale are rated on a 5-point scale and questions are phrased in such a way as to ensure that 1 is always equated with the most favorable perception of vaccination, and 5 is the most unfavorable.
• Number of participants with change in Dimension Scores Using PIN Questionnaire - D2I [ Time Frame: At Months 1, 5, and 11 ]
  The PIN questionnaire explores the bother of pain at the injection site and injection site reaction (ISRs), anxiety before and after injection, willingness to receive an HIV injectable treatment the following visit and satisfaction with the mode of treatment administration of individuals receiving injection and perceptions of individuals associated with receiving injections. This measure contains 21 items that measure pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside of a clinical trial. The items in the scale are rated on a 5-point scale and questions are phrased in such a way as to ensure that 1 is always equated with the most favorable perception of vaccination, and 5 is the most unfavorable.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate Efficacy and Safety of Cabotegravir (CAB) Long Acting (LA) Plus (+) Rilpivirine (RPV) LA Versus BIKTARVY® (BIK) in Participants With Human Immunodeficiency Virus (HIV)-1 Who Are Virologically Suppressed
• Official Title: A Phase IIIb, Randomized, Multicenter, Active-controlled, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine Administered Every Two Months From a Bictegravir/Emtricitabine/Tenofovir Alafenamide Single Tablet Regimen in HIV-1 Infected Adults Who Are Virologically Suppressed
• Brief Summary: This study is designed to assess the antiviral activity and safety of a two-drug regimen of CAB LA + RPV LA compared with maintenance of BIK. BIKTARVY is a registered trademark of Gilead Sciences.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infections

Intervention

• Drug: Cabotegravir Tablets
  CAB tablets will be available as film coated tablets for oral administration.
• Drug: Cabotegravir Injectable Suspension (CAB LA)
  CAB LA will be available as sterile suspension for injection in GSK1265744 for administration as IM injection.
• Drug: Rilpivirine Tablets
  RPV will be administered as tablets for oral administration.
• Drug: Rilpivirine Injectable Suspension (RPV LA)
  RPV LA will be available as a sterile suspension of RPV to be administered as an IM injection.
• Drug: BIKTARVY Tablets (BIK)
  BIK will be a three-drug fixed dose combination product BIC, FTC, and TAF for oral administration.

Study Arms

• Experimental: Participants receiving CAB LA + RPV LA regimen
  Participants will be offered the option to start with a month long oral lead in or to start long acting intramuscular (IM) injections (oral lead in [OLI] or direct to injection [D2I]). On Day 1, participants who choose to participate in OLI will be administered CAB + RPV orally for one month. At the Month 1 visit, last dose of oral CAB + RPV will be given followed by the first CAB LA + RPV LA IM injection. The second IM injection with CAB LA and RPV LA will be administered at Month 2 followed by the same administered every 2 months (Q2M) until Month 12. In D2I, at Day 1, eligible participants will receive the first injection of CAB LA + RPV LA as initial loading dose. The second and third injections (CAB LA + RPV LA) will be administered at Month 1 and Month 3 followed by the same Q2M until Month 11.
  Interventions:

  • Drug: Cabotegravir Tablets
  • Drug: Cabotegravir Injectable Suspension (CAB LA)
  • Drug: Rilpivirine Tablets
  • Drug: Rilpivirine Injectable Suspension (RPV LA)
• Active Comparator: Participants receiving BIK

  Participants will receive BIK, that is a combination of Bictegravir (BIC) + Emtricitabine (FTC)

  + Tenofovir alafenamide (TAF) orally, administered until Month 12.

  Intervention: Drug: BIKTARVY Tablets (BIK)

• Publications *: Karver TS, Pascual-Bernaldez M, Berni A, Hnoosh A, Castagna A, Messiaen P, Puerto MJG, Bloch M, Adachi E, Sinclair G, Felizarta F, Angel JB, Sutton K, Sutherland-Phillips D, D'Amico R, Kerrigan D. Factors Associated with Health Care Providers' Preference for Forgoing an Oral Lead-In Phase When Initiating Long-Acting Injectable Cabotegravir and Rilpivirine in the SOLAR Clinical Trial. AIDS Patient Care STDS. 2023 Jan;37(1):53-59. doi: 10.1089/apc.2022.0168.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 12, 2023): 687
• Original Estimated Enrollment (submitted: September 1, 2020): 654
• Actual Study Completion Date: April 17, 2023
• Actual Primary Completion Date: July 13, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants aged 18 years or older (or >=19 where required by local regulatory agencies), at the time of signing the informed consent.

• A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test at screen and a negative urine hCG test at Randomization), not lactating, and at least one of the following conditions applies.

  1. Non-reproductive potential defined as:

     • Pre-menopausal females with one of the following:

       1. Documented tubal ligation.
       2. Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion.
       3. Hysterectomy.
       4. Documented Bilateral Oophorectomy
     • Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
  2. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication, throughout the study, for at least 30 days after discontinuation of all oral study medications, and for at least 52 weeks after discontinuation of CAB LA and RPV LA.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible participants or their legal guardians (and next of kin when locally required), must sign a written Informed Consent Form before any protocol-specified assessments are conducted. Enrollment of participants who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct protocol procedures.
• Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.
• Must be on the uninterrupted current regimen of BIK for at least 6 months prior to Screening with an undetectable HIV-1 viral load for at least 6 months prior to Screening. BIK must be the participant's first or second regimen. If BIK is the second regimen, the first regimen must be an integrase inhibitor (INI) regimen. Only a single prior Integrase inhibitor (INI) regimen is allowed if BIK is a second line regimen >=6 months prior to screening. Any history of non-integrase strand transfer inhibitor regimens (that is. non-nucleoside reverse transcriptase inhibitor, protease inhibitor, C-C chemokine receptor 5 and other entry inhibitors) are not permitted. Any prior change in regimen, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must not have been done for treatment failure (HIV-1 RNA >=400 c/mL).

The following are limited exceptions:

• A change from Tenofovir disoproxil fumarate (TDF) to TAF will not be considered a regimen change.
• Historical perinatal use of Nucleoside reverse transcriptase inhibitor (NRTI) when given in addition to an ongoing Highly active antiretroviral therapy (HAART) will not be considered a change in ART therapy regimen.
• The past use of ARVs in the context of Post Exposure Prophylaxis (PEP) or Pre-Exposure Prophylaxis (PrEP) while the participant was HIV negative will be allowed. Such cases will be evaluated on a case by case basis with the Medical Monitor, and may require documentation of HIV negative serology during time of PEP or PrEP.
• A change in dosing scheme of the same drug from twice daily to once daily will not be considered a change in ART regimen if data support similar exposures and efficacy.

• A change in formulation from multiple class regimens to single treatment regimens (of the same medications) would not be considered a change in ART regimen.

  • Documented evidence of plasma HIV-1 RNA measurements <50 c/mL in the 6 months prior to Screening.
  • Plasma HIV-1 RNA <50 c/mL at Screening.

Exclusion Criteria:

• Within 6 months prior to Screening, any plasma HIV-1 RNA measurement >=50 c/mL.
• Within the 6 to 12-month window prior to Screening, documented evidence of any plasma HIV-1 RNA measurement greater than (>)200 c/mL, or 2 or more plasma HIV-1 RNA measurements >=50 c/mL.
• History of prior treatment failure to any Department of Health and Human Services (DHHS) recommended ART regimen.
• History of drug holiday >1 month for any reason prior to Screening visit, except where all ART was stopped due to tolerability and/or safety concerns.
• Any change to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV 1 RNA measurement >=200 c/mL after initial suppression to <50 c/mL while on first line HIV therapy regimen).
• Participants who are currently participating in or anticipate being selected for any other interventional study.
• Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
• Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3 disease except cutaneous Kaposi's sarcoma not requiring systemic therapy, and CD4+ counts <200 cells/microliter are not exclusionary.
• Participants with moderate to severe hepatic impairment.
• Any pre-existing physical or mental condition (including substance use disorder) 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.
• Participants determined by the Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrollment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrollment.

• All participants will be screened for syphilis.

  • Participants with untreated secondary (late latent) or tertiary syphilis infection, defined as a positive rapid plasma reagin (RPR) and a positive treponemal test without clear documentation of treatment, are excluded.
  • Participants with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor.
  • Participants with primary syphilis or early latent secondary syphilis (acquired within the preceding year) who have a positive RPR test and have not been treated may be treated during the screening period and if completion of antibiotic treatment occurs during the screening period, may be allowed entry after consultation with the Medical Monitor. If antibiotic treatment cannot be completed before the screening window ends, participants may be rescreened once following completion of antibiotic therapy for primary or early latent secondary syphilis.
• Participants who, in the investigator's judgment, pose a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
• The participant has a tattoo, gluteal implant/enhancements or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions.

• 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 deoxyribonucleic acid (DNA) as follows:

  1. Participants positive for HBsAg are excluded.
  2. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status), whether negative or positive for HBV DNA, are excluded.
• Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; participants who require or qualify for immediate HCV treatment are excluded for those co-infected participants who post entry into Switch Onto Long Acting Regimen (SOLAR) decide treatment for HCV infection is warranted or desired either by the participant or by the treating physician.

Participants with HCV co-infection will be allowed entry into this study if:

1. Liver enzymes meet entry criteria
2. HCV Disease has undergone appropriate work-up, and is not advanced, and will not require treatment prior to the Month 14 visit. Additional information (where available) on participants with HCV co-infection at screening should include results from any liver biopsy, Fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment.
3. In the event that recent biopsy or imaging data is not available or inconclusive, the fibrosis (Fib)-4 score will be used to verify eligibility

i. Fib-4 score >3.25 is exclusionary ii. Fib-4 scores 1.45-3.25 requires Medical Monitor consultation Fibrosis 4 Score Formula: d. Age x aspartate aminotransferase (AST)/ Platelets x (square [Alanine aminotransferase {ALT}]).

• Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis, or decompensated cirrhosis [for example {e.g.} ascites, encephalopathy, or variceal bleeding]), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
• History of liver cirrhosis with or without hepatitis viral co-infection.
• Ongoing or clinically relevant pancreatitis
• Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease.
• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the participant prior to randomization.
• Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication.
• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class. In addition, if heparin is used during pharmacokinetic (PK) sampling, participants with a history of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled.
• Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (less than or equal to [<=]325 milligram) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
• Corrected QT interval (QTc [Bazett]) >450 milliseconds (msec) or QTc (Bazett) >480 msec for participants with bundle branch block.
• Known or suspected active Coronavirus Disease-2019 (COVID-19) infection or has had contact with an individual with known COVID-19, within 14 days of study enrollment.
• Known or suspected presence of resistance mutations as defined by the International Antiviral Society-United States of America (IAS-USA) resistance guidelines to the individual components of BIK (BIC, FTC, TAF), RPV, and CAB by any historical resistance test result.
• Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening phase to verify a result.
• Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.
• Participant has estimated creatine clearance <30mL/minute per 1.73 meter square (m^2) via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method.
• ALT >=3 times upper limit of normal (ULN).
• Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to Day 1 of this study.

• Treatment with any of the following agents within 28 days of Screening:

  • radiation therapy;
  • cytotoxic chemotherapeutic agents;
  • tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid/INH);
  • anti-coagulation agents;
  • Immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons.
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
• Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 within 28 days of study Day 1. Treatment with acyclovir/valacyclovir is permitted.
• Use of medications which are associated with Torsade de Pointes.
• Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, France, Germany, Ireland, Italy, Japan, Netherlands, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT04542070
• Other Study ID Numbers: 213500
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on ViiV's data sharing criteria can be found at: https://viivhealthcare.com/about-viiv/corporate-ethics-compliance/commitment-to-data-transparency/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• URL: https://viivhealthcare.com/about-viiv/corporate-ethics-compliance/commitment-to-data-transparency/

• Current Responsible Party: ViiV Healthcare
• Original Responsible Party: Same as current
• Current Study Sponsor: ViiV Healthcare
• Original Study Sponsor: Same as current
• Collaborators: Janssen, LP

Investigators

• Study Director: GSK Clinical Trials; ViiV Healthcare

• PRS Account: ViiV Healthcare
• Verification Date: August 2023