This Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS-2M) study is designed to demonstrate the non-inferior antiviral activity and safety of CAB LA + RPV LA administered every 8 weeks (Q8W) compared to CAB LA + RPV LA administered every 4 weeks (Q4W) over a 48-week treatment period in approximately 1020 adult HIV-1 infected subjects. Subjects will be divided in 2 groups; Group 1 will include subjects receiving current anti-retroviral (ART) standard of care (SOC) therapy whereas group 2 will include subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in both groups will be randomized to receive CAB LA + RPV LA Q4W or Q8W. The study will be carried out in 3 phases including screening phase, maintenance phase and extension phase. Subjects choosing not to enter the Extension phase can complete their study participation at the Week 100 visit and enter into the 52-week Long-Term Follow-Up (LTFU) Phase as required.
Name: Cabotegravir Tablets
Description: CAB tablets are white to almost white oval shaped film coated 30 mg tablets for oral administration. CAB tablets are to be stored up to 30 degree Celsius and protected from moisture.Type: DrugSubjects in group 1 receiving study treatment once in 4 weeks Subjects in group 1 receiving study treatment once in 8 weeks
Name: Rilpivirine Tablets
Description: RPV tablets are 25 mg tablets that are off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". RPV tablets should be stored at 25 degree Celsius (excursions permitted to 15 degree-30 degree Celsius) and protected from light.Type: DrugSubjects in group 1 receiving study treatment once in 4 weeks Subjects in group 1 receiving study treatment once in 8 weeks
Name: Cabotegravir Injectable Suspension
Description: CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be freezed.Type: DrugSubjects in group 1 receiving study treatment once in 4 weeks Subjects in group 1 receiving study treatment once in 8 weeks Subjects in group 2 receiving study treatment once in 4 weeks Subjects in group 2 receiving study treatment once in 8 weeks
Name: Rilpivirine Injectable Suspension
Description: RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be freezed. RPV LA should also be protected from light.Type: DrugSubjects in group 1 receiving study treatment once in 4 weeks Subjects in group 1 receiving study treatment once in 8 weeks Subjects in group 2 receiving study treatment once in 4 weeks Subjects in group 2 receiving study treatment once in 8 weeks
Description: Virologic outcome for each subject will be calculated according to the food and drug administration's (FDA) Snapshot algorithm. As defined by the Snapshot algorithm, HIV-RNA >=50 copies/mL is determined by the last available HIV-1 RNA measurement while the subject is on treatment within the analysis visit window of interest.
Measure: Percentage of subjects with plasma HIV ribonucleic acid (RNA) >=50 copies per milliliter (copies/mL) at Week 48 Time: Week 48Description: The antiviral and immunologic activity of CAB LA + RPV LA Q8W will be compared to CAB LA + RPV LA Q4W at Week 24, Week 48 and Week 96 using the FDA Snapshot algorithm. Subjects with last available HIV-1 RNA measurement <50 copies/mL while the subject is on treatment within the analysis visit window of interest are classified as responders; subjects without evaluable HIV-RNA data for the visit of interest or who change treatment not permitted per protocol before the analysis window are considered non-responders.
Measure: Percentage of subjects with plasma HIV-1 RNA <50 copies/mL Time: Up to Week 96Description: CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 copies/mL after prior suppression to <200 copies/mL. CVF will be analyzed through Week 24, Week 48 and Week 96 as a measure of antiviral and immunologic activity of CAB LA and RPV LA.
Measure: Percentage of subjects with protocol-defined confirmed virologic failure (CVF) Time: Up to Week 96Description: Virologic outcome for each subject will be calculated according to the FDA Snapshot algorithm. As defined by the Snapshot algorithm, HIV-RNA >=50 copies/mL is determined by the last available HIV-1 RNA measurement while the subject is on treatment within the analysis visit window of interest.
Measure: Percentage of subjects with HIV-RNA >=50 copies/mL Time: Up to Week 96Description: Change from Baseline in viral load will be assessed over time including Week 48 and Week 96.
Measure: Change from Baseline in viral load Time: Baseline and Up to Week 96Description: Lymphocyte subsets will be collected for assessment by flow cytometry at specific time points including Week 48 and Week 96.
Measure: Change from Baseline in cluster of differentiation (CD)4+ cell counts Time: Baseline and Up to Week 96Description: An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Measure: Number of subjects with Adverse events (AEs) and serious AEs Time: Up to Week 96Description: Clinical chemistry parameters including blood urea nitrogen (BUN), creatinine, glucose, sodium, potassium, chloride, total carbon-di-oxide (CO2), lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, phosphate, total bilirubin, albumin, creatine phosphokinase and lipid panel will be analyzed as a measure of safety.
Measure: Number of subjects with abnormal clinical chemistry values Time: Up to Week 96Description: Clinical hematology parameters including platelet count, red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscle volume (MCV), neutrophils, lymphocytes, monocytes, eosinophils and basophils will be analyzed as a measure of safety.
Measure: Number of subjects with abnormal clinical hematology values Time: Up to Week 96Description: Subjects who discontinue treatment due to AEs will be analyzed as a measure of safety.
Measure: Percentage of subjects who discontinue treatment due to AEs Time: Up to Week 96Description: Change from Baseline in albumin will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in albumin Time: Baseline and up to Week 96Description: Change from Baseline in Alkaline phosphatase, ALT, AST, creatine phosphokinase, lipase will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in Alkaline phosphatase, ALT, AST, creatine phosphokinase, lipase Time: Baseline and up to Week 96Description: Change from Baseline in total bilirubin and creatinine will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in total bilirubin and creatinine Time: Baseline and up to Week 96Description: Change from Baseline in glucose, sodium, potassium, total CO2, BUN, chloride, phosphate will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in glucose, sodium, potassium, total CO2, BUN, chloride, phosphate Time: Baseline and up to Week 96Description: Change from Baseline in total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in total cholesterol, High density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides Time: Baseline and Up to Week 96Description: Change from Baseline in creatinine clearance will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in creatinine clearance Time: Baseline and Up to Week 96Description: Change from Baseline in basophils, eosinophils, monocytes, lymphocytes, neutrophils and platelet count will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in basophils, eosinophils, monocytes, lymphocytes, neutrophils and platelet count Time: Baseline and Up to Week 96Description: Change from Baseline in hematocrit levels will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in hematocrit levels Time: Baseline and Up to Week 96Description: Change from Baseline in hemoglobin levels will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in hemoglobin levels Time: Baseline and Up to Week 96Description: Change from Baseline in RBC count will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in RBC count Time: Baseline and Up to Week 96Description: Change from Baseline in WBC count will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in WBC count Time: Baseline and Up to Week 96Description: Change from Baseline in MCV levels will be assessed up to long-term follow-up visits as a measure of safety.
Measure: Change from Baseline in MCV levels Time: Baseline and Up to Week 96Description: Whole venous blood samples will be obtained from each subject for analysis of potential genotypic resistance to CAB, RPV.
Measure: Number of incidences of treatment emergent genotypic resistance Time: Up to Week 96Description: Whole venous blood samples will be obtained from each subject for analysis of potential phenotypic resistance to CAB, RPV.
Measure: Number of incidences of treatment emergent phenotypic resistance Time: Up to Week 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
Measure: Trough plasma concentration (Ctrough) of CAB LA: Q4W dosing Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
Measure: Ctrough of RPV LA: Q4W dosing Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
Measure: Ctrough of CAB LA: Q8W dosing Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
Measure: Ctrough of RPV LA: Q8W dosing Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
Measure: Maximum plasma concentration (Cmax) of CAB LA: Q4W dosing Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
Measure: Cmax of RPV LA: Q4W dosing Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
Measure: Cmax of CAB LA: Q8W dosing Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
Measure: Cmax of RPV LA: Q8W dosing Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
Measure: Area under the curve (AUC) of CAB LA: Q4W dosing Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
Measure: AUC of RPV LA: Q4W dosing Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
Measure: AUC of CAB LA: Q8W dosing Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
Measure: AUC of RPV LA: Q8W dosing Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96Description: Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters will be evaluated as potential predictors of inter participant variability for pharmacokinetic parameters.
Measure: Number of subjects with different demographic parameters: For inter-participant variability Time: Up to Week 96Description: Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters will be evaluated as potential predictors of inter participant variability for pharmacokinetic parameters.
Measure: Number of subjects with different demographic parameters: For intra participant variability Time: Up to Week 96Description: The HAT-QoL is a 42-item questionnaire grouped into nine dimensions, assessing overall function and well-being. A shorter version of this original HAT-QoL will be used in the present study which will contain 14-items grouped into the three following dimensions: "life satisfaction", "disclosure worries" and "HIV medication". All items use a ''past 4 weeks'' timeframe and a Likert response scale from 1=''all of the time'' to 5=''none of the time''.
Measure: Change from Baseline in health related quality of life (HRQoL) of subjects using the HIV/Acquired immunodeficiency syndrome (AIDS) Targeted Quality of Life (HAT-QoL) questionnaire Time: Baseline and up to Week 48Description: HIVTSQ is a 10-item questionnaire which is used specifically to measure satisfaction with medication for people infected with HIV.
Measure: Change from Baseline in total "treatment satisfaction" score of the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) Time: Baseline and up to Week 48Description: HIVTSQ is a 10-item questionnaire which is used specifically to measure satisfaction with medication for people infected with HIV.
Measure: Change from Baseline in individual item score of HIVTSQs Time: Baseline and Up to Week 48Description: HIVTSQc is the change version of original HIVTSQs. HIVTSQc enhances the sensitivity by allowing those who were satisfied at Baseline to express even greater satisfaction at follow-up.
Measure: Change in treatment satisfaction using the HIV Treatment Satisfaction Change Questionnaire (HIVTSQc) Time: Week 48Description: Change from Week 8 in dimension score which assess Bother of Injection Site Reactions (ISRs), Leg movement, Sleep, and Injection Acceptance will be evaluated using PIN questionnaire. This measure contains 21 items and scores range from 1 to 5 where 1= the most favorable perception of vaccination while 5= the most unfavorable.
Measure: Change from Week 8 in Dimension scores using the Perception of injection questionnaire (PIN) Time: Week 8 and up to Week 48Description: Change from Week 8 in individual item scores which assess pain during injection, anxiety before and after injection, willingness to be injected in the future and overall satisfaction with mode of administration over time will be evaluated using the PIN questionnaire. This measure contains 21 items and scores range from 1 to 5 where 1= the most favorable perception of vaccination while 5= the most unfavorable.
Measure: Change from Week 8 in individual item score using PIN Time: Week 8 and Up to Week 48Description: The ACCEPT questionnaire, a 25 item questionnaire, is a generic medication acceptance measure assessing how patients weigh advantages and disadvantages of long-term medications. The study will use three questions that focus on general acceptance of study medication.
Measure: Change from Baseline in treatment acceptance using the "General acceptance" dimension of the Chronic Treatment Acceptance (ACCEPT) questionnaire Time: Baseline and up to Week 48Description: Lymphocyte subsets will be collected for assessment by flow cytometry at specific time points including Week 48 and Week 96.
Measure: CD4+ cell counts Time: Baseline and up to Week 96Description: The preference questionnaire will include 3 questions evaluating preference of HIV treatment and the attributes supporting this preference. It will assess will assess whether subjects prefer the CAB LA + RPV LA injectable treatment.
Measure: Number of subjects preferring CAB LA+ RPV LA injectable treatment, using preference questionnaire Time: Week 48Description: The preference questionnaire will include 3 questions evaluating preference of HIV treatment and the attributes supporting this preference. It will assess will assess whether subjects prefer the CAB LA + RPV LA Q8W injectable treatment.
Measure: Number of subjects preferring CAB LA + RPV LA Q8W, using preference questionnaire Time: Week 48Allocation: Randomized
Parallel Assignment
There is one SNP
- Any evidence of primary resistance based on the presence of any major known Integrase inhibitor (INI) or Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutation, except for K103N by any historical resistance test result. --- K103N ---