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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02951052




Registration number
NCT02951052
Ethics application status
Date submitted
15/09/2016
Date registered
1/11/2016

Titles & IDs
Public title
Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults
Scientific title
A Phase III, Randomized, Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current INI- NNRTI-, or PI-based Antiretroviral Regimen in HIV-1-infected Adults Who Are Virologically Suppressed
Secondary ID [1] 0 0
2016-001647-39
Secondary ID [2] 0 0
201585
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infection, Human Immunodeficiency Virus 0 0
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cabotegravir (CAB) tablet
Treatment: Drugs - Rilpivirine (RPV) tablet
Treatment: Drugs - Cabotegravir - Injectable Suspension (CAB LA)
Treatment: Drugs - Rilpivirine - Injectable Suspension (RPV LA)
Treatment: Drugs - 2 NRTIs plus an INI, NNRTI, or PI

Experimental: CAB LA + RPV LA every 4 weeks - Eligible subjects receive Oral CAB 30 mg + RPV 25 mg once daily for four weeks, IM CAB LA 600 mg and RPV LA 900 mg for the first injection, and Week 4 onwards subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks until withdrawal.

Active comparator: Current antiretroviral regimen - Eligible subjects will continue their current anti-retroviral regimen (2 NRTIs plus an INI, NNRTI, or a PI) for 52 weeks. After 52 weeks subjects have the option to continue study participation by switching to CAB LA + RPV LA in the Extension Phase where they will follow the procedure of CAB LA + RPV LA arm.


Treatment: Drugs: Cabotegravir (CAB) tablet
It is a white oval shaped film coated 30 mg tablets for oral administration. CAB Tablet is composed of cabotegravir sodium, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, magnesium stearate, and white film-coat

Treatment: Drugs: Rilpivirine (RPV) tablet
It is a 25 mg tablet with off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". Each tablet contains RPV hydrochloride, and the inactive ingredients croscarmellose sodium, lactose monohydrate, magnesium stearate, polysorbate 20, povidone K30 and silicified microcrystalline cellulose

Treatment: Drugs: Cabotegravir - Injectable Suspension (CAB LA)
It is a sterile white to slightly pink suspension containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) injection. Each vial is for single-dose use containing a withdrawable volume of 2.0 mL, and does not require dilution prior to administration. CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection

Treatment: Drugs: Rilpivirine - Injectable Suspension (RPV LA)
It is a sterile white suspension containing 300 mg/mL of RPV as the free base. The route of administration is by intramuscular (IM) injection. Each vial contains a nominal fill of 2.0 mL, and does not require dilution prior to administration. RPV LA requires refrigeration and must be protected from light. RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection.

Treatment: Drugs: 2 NRTIs plus an INI, NNRTI, or PI
Acceptable stable (initial or second) ARV regimens include 2 NRTIs plus:

* INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen)
* NNRTI (either the initial or second cART regimen)
* Boosted PI (or atazanavir \[ATV\] unboosted) (either the initial or second PI-based cART regimen)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Virologic Failure (HIV-1 Ribonucleic Acid [RNA] >=50 Copies Per Millilter [mL]) Using Snapshot Algorithm at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Number of Participants With HIV-1 RNA <50 Copies/mL Using Snapshot Algorithm at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
Number of Participants With HIV-1 RNA <200 Copies/mL Using Snapshot Algorithm at Week 48
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
Number of Participants With Confirmed Virologic Failure (CVF)
Timepoint [3] 0 0
Weeks 8, 12, 20, 24, 32 and 40
Secondary outcome [4] 0 0
Absolute Values for Plasma HIV-1 RNA at Week 48
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
Change From Baseline Values for Plasma HIV-1 RNA
Timepoint [5] 0 0
Baseline and Week 48
Secondary outcome [6] 0 0
Absolute Values for CD4+ Lymphocyte Count at Week 48
Timepoint [6] 0 0
Week 48
Secondary outcome [7] 0 0
Change From Baseline Values for CD4+ Lymphocyte Count at Week 48
Timepoint [7] 0 0
Baseline (Day 1) and Week 48
Secondary outcome [8] 0 0
Number of Participants With Disease Progression
Timepoint [8] 0 0
Up to Week 48
Secondary outcome [9] 0 0
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Timepoint [9] 0 0
Up to Week 48
Secondary outcome [10] 0 0
Number of Participants With Severity of Adverse Events
Timepoint [10] 0 0
Up to Week 48
Secondary outcome [11] 0 0
Absolute Values for Hematology Parameters Over Time Including Week 48: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets
Timepoint [11] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [12] 0 0
Absolute Values for Hematology Parameters: Erythrocyte Mean Corpuscular Volume
Timepoint [12] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [13] 0 0
Absolute Values for Hematology Parameters: Erythrocytes
Timepoint [13] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [14] 0 0
Absolute Values for Hematology Parameters: Hemoglobin
Timepoint [14] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [15] 0 0
Absolute Values for Hematology Parameters: Hematocrit
Timepoint [15] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [16] 0 0
Change From Baseline for Hematology Parameters: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets
Timepoint [16] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [17] 0 0
Change From Baseline for Hematology Parameters: Erythrocyte Mean Corpuscular Volume
Timepoint [17] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [18] 0 0
Change From Baseline for Hematology Parameters: Erythrocytes
Timepoint [18] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [19] 0 0
Change From Baseline for Hematology Parameters: Hematocrit
Timepoint [19] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [20] 0 0
Change From Baseline for Hematology Parameters: Hemoglobin
Timepoint [20] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [21] 0 0
Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatinine Kinase (CK)
Timepoint [21] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [22] 0 0
Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin
Timepoint [22] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [23] 0 0
Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
Timepoint [23] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [24] 0 0
Absolute Values for Clinical Chemistry Parameters: Total Carbon-dioxide (CO2), Chloride, Glucose, Phosphate, Potassium, Sodium and Urea Over Time Including Week 48
Timepoint [24] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [25] 0 0
Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase
Timepoint [25] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [26] 0 0
Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance
Timepoint [26] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [27] 0 0
Number of Participants With Abnormal Urinalysis Parameters Over Time Including Week 48
Timepoint [27] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48.
Secondary outcome [28] 0 0
Number of Participants With Urine Potential of Hydrogen (pH) Over Time Including Week 48
Timepoint [28] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [29] 0 0
Change From Baseline in Clinical Chemistry Parameters Over Time Including Week 48: ALT, ALP, AST and CK
Timepoint [29] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [30] 0 0
Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin
Timepoint [30] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [31] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
Timepoint [31] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [32] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48
Timepoint [32] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [33] 0 0
Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase
Timepoint [33] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [34] 0 0
Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance.
Timepoint [34] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [35] 0 0
Change From Baseline Values for Fasting Lipid Panel Over Time Including Week 48
Timepoint [35] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [36] 0 0
Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Over Time Including Week 48
Timepoint [36] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [37] 0 0
Change From Baseline Values in Urine Creatinine Over Time Including Week 48
Timepoint [37] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [38] 0 0
Change From Baseline Values in Urine Phosphate Over Time Including Week 48
Timepoint [38] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [39] 0 0
Change From Baseline Values in Urine Retinol Binding Protein Over Time Including Week 48
Timepoint [39] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [40] 0 0
Change From Baseline Values in Urine Specific Gravity Over Time Including Week 48
Timepoint [40] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [41] 0 0
Change From Baseline Values in Urine pH Over Time Including Week 48
Timepoint [41] 0 0
Baseline (Day 1) and at Weeks 4, 24 and 48
Secondary outcome [42] 0 0
Number of Participants Who Discontinued or Withdrawn Due to AEs Over Time Including Week 48
Timepoint [42] 0 0
Up to Week 48
Secondary outcome [43] 0 0
Percentage Change From Baseline in Fasting Lipids Overtime Including Week 48
Timepoint [43] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [44] 0 0
Number of Participants With Phenotypic Resistance Through Week 48
Timepoint [44] 0 0
At the time of CVF
Secondary outcome [45] 0 0
Number of Participants With Genotypic Resistance Through Week 48
Timepoint [45] 0 0
At the time of CVF
Secondary outcome [46] 0 0
Number of Participants With AEs by Using Baseline Third Agent Treatment Class Overtime Including Week 48
Timepoint [46] 0 0
Up to Week 48
Secondary outcome [47] 0 0
Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: ALT, ALP, AST and CK
Timepoint [47] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [48] 0 0
Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Albumin
Timepoint [48] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [49] 0 0
Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
Timepoint [49] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [50] 0 0
Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Creatinine Clearance
Timepoint [50] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [51] 0 0
Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Lipase
Timepoint [51] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [52] 0 0
Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48
Timepoint [52] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [53] 0 0
Absolute Values for Fasting Lipid Panel Using Baseline Third Agent Treatment Class Overtime Including Week 48
Timepoint [53] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [54] 0 0
Number of Participants Discontinued or Withdrawn Due to AEs When Baseline Third Agent Treatment Class Was Used Over Time Including Week 48
Timepoint [54] 0 0
Up to Week 48
Secondary outcome [55] 0 0
Plasma Trough Concentration (Ctrough) for CAB LA Evaluable
Timepoint [55] 0 0
Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [56] 0 0
Ctrough for RPV LA Evaluable
Timepoint [56] 0 0
Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [57] 0 0
Area Under the Curve (AUC) for CAB LA
Timepoint [57] 0 0
Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5 and 41
Secondary outcome [58] 0 0
AUC for RPV LA
Timepoint [58] 0 0
Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5 and 41
Secondary outcome [59] 0 0
Maximum Concentration (Cmax) in Plasma for CAB LA Evaluable at Week 41
Timepoint [59] 0 0
Week 41- 1 Week post dose
Secondary outcome [60] 0 0
Cmax in Plasma for RPV LA Evaluable at Week 41
Timepoint [60] 0 0
Week 41- 1 Week post dose
Secondary outcome [61] 0 0
Percentage of Participants With a Virologic Failure Using Snapshot Algorithm by Baseline Third Agent
Timepoint [61] 0 0
Week 48
Secondary outcome [62] 0 0
Percentage of Participants With Plasma HIV-1 RNA <50copies/mL Using Snapshot Algorithm by Baseline Third Agent
Timepoint [62] 0 0
Week 48
Secondary outcome [63] 0 0
Number of Participants With Severity of Adverse Events by Baseline Third Agents
Timepoint [63] 0 0
Up to Week 48
Secondary outcome [64] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: ALT, ALP, AST and CK
Timepoint [64] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [65] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Albumin
Timepoint [65] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [66] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Bilirubin, Direct Bilirubin and Creatinine
Timepoint [66] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [67] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Creatinine Clearance
Timepoint [67] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [68] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Lipase
Timepoint [68] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [69] 0 0
Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48
Timepoint [69] 0 0
Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcome [70] 0 0
Change From Baseline Values for Fasting Lipid Panel Using Baseline Third Agent Treatment Class Overtime Including Week 48
Timepoint [70] 0 0
Baseline (Day 1) and at Week 48
Secondary outcome [71] 0 0
Number of Participants With Genotypic Resistance Using Baseline Third Agent Through Week 48
Timepoint [71] 0 0
At the time of CVF
Secondary outcome [72] 0 0
Number of Participants With Phenotypic Resistance Using Baseline Third Agent Through Week 48
Timepoint [72] 0 0
At the time of CVF
Secondary outcome [73] 0 0
Change From Week 5 in Dimension Scores Using Percerption of Injection Questionnaire (PIN)-Last Observation Carried Forward (LOCF) in Q4W Arm
Timepoint [73] 0 0
Week 5 and at Weeks 41 and 48
Secondary outcome [74] 0 0
Percentage of Participants With Extremely or Very Acceptable Pain and Local Reaction: Acceptability Score on PIN Questionnaire in Q4W Arm
Timepoint [74] 0 0
Weeks 5, 41 and 48
Secondary outcome [75] 0 0
Change From Baseline in Life Satisfaction (LISAT) Using HIV/AIDs-targeted Quality of Life (HATQoL) Questionnaire
Timepoint [75] 0 0
Baseline (Day 1) and at Weeks 24 and 48
Secondary outcome [76] 0 0
Change From Baseline in HIV Medication, MEDWO Using HATQoL
Timepoint [76] 0 0
Baseline and at Weeks 24 and 48
Secondary outcome [77] 0 0
Change From Baseline in DISWO Using HATQoL
Timepoint [77] 0 0
Baseline and at Weeks 24 and 48
Secondary outcome [78] 0 0
Change From Baseline in Health Status Using 12-item Short Form Survey (SF-12)
Timepoint [78] 0 0
Baseline and at Weeks 24 and 48
Secondary outcome [79] 0 0
Change From Baseline in Total Treatment Satisfaction Using HIV Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4b, 24 and 44
Timepoint [79] 0 0
Baseline and at Weeks 4b, 24 and 44
Secondary outcome [80] 0 0
Change in Treatment Satisfaction Over Time Using HIVTSQ Change (HIVTSQc) at Week 48 in Q4W Arm
Timepoint [80] 0 0
Week 48
Secondary outcome [81] 0 0
Change From Baseline in Treatment Acceptance at Weeks 8, 24 and 48 Using "General Acceptance" Dimension of the Chronic Treatment Acceptance (ACCEPT) Questionnaire
Timepoint [81] 0 0
Baseline and at Weeks 8, 24 and 48
Secondary outcome [82] 0 0
Change From 4b in Tolerability of Injection at Week 5, 40 and 41 Using Numeric Rating Scale (NRS) Within CAB LA+RPV LA Arm
Timepoint [82] 0 0
Weeks 4b, 5, 40 and 41
Secondary outcome [83] 0 0
Change From Baseline in Individual Item Scores of HIVTSQc at Weeks 4b, 24 and 44
Timepoint [83] 0 0
Baseline and Weeks 4b, 24 and 44

Eligibility
Key inclusion criteria
* Aged 18 years or older (or =19 where required by local regulatory agencies), at the time of signing the informed consent.
* Must be on uninterrupted current regimen (either the initial or second ARV regimen) for at least 6 months prior to Screening. Any prior switch, 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).
* Acceptable stable (initial or second) ARV regimens prior to Screening include 2 NRTIs plus: INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen);NNRTI (either the initial or second cART regimen);Boosted PI (or atazanavir [ATV] unboosted) (must be either the initial cART regimen or one historical within class switch is permitted due to safety/tolerability) The addition, removal, or switch of a drug(s) that has been used to treat HIV based on antiretroviral properties of the drug constitutes a change in ART with the following limited exceptions: Historical changes in formulations of ART drugs or booster drugs will not constitute a change in ART regimen if the data support similar exposures and efficacy, and the change must have been at least 3 months prior to Screening; Historical perinatal use of an NRTI when given in addition to an ongoing HAART will not be considered a change in ART regimen; 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.
* Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening;
* Plasma HIV-1 RNA <50 c/mL at Screening;
* A female subjects is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (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: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up; confirmation of bilateral tubal occlusion; Hysterectomy; 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 enrolment.
2. Reproductive potential and agrees to 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, and until from 30 days prior to the first dose of study medication throughout the study, and 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. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form. Eligible subjects 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. Enrolment of subjects 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.
* Subjects enrolled in France must be affiliated to, or a beneficiary of, a social security category.
* All subjects participating in the study should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement =50 c/mL
* Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL, or 2 or more plasma HIV-1 RNA measurements =50 c/mL
* Any drug holiday during the window between initiating first HIV ART and 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns
* Any switch 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 =400 c/mL after initial suppression to <50 c/mL while on first line HIV therapy regimen)
* Abacavir/dolutegravir/lamivudine, (ABC/DTG/3TC) as current ART regimen
* A history of use of any regimen consisting of only single NNRTI therapy (even if only for peri-partum treatment), or only single or dual NRTI therapy prior to starting cART
* Subjects who are currently participating in or anticipate to be selected for any other interventional study
* Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study
* Any evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells/mm^3
* Subjects 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 subjects ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject.
* Subjects determined by the Investigator to have a high risk of seizures, including subjects with an unstable or poorly controlled seizure disorder. A subject with a prior history of seizure may be considered for enrolment 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 enrolment
* All subjects will be screened for syphilis (rapid plasma reagin [RPR]). Subjects with untreated syphilis infection, defined as a positive RPR without clear documentation of treatment, are excluded. Subjects with a serofast RPR result (persistence of a reactive nontreponemal syphilis test) despite history of adequate therapy and no evidence of re-exposure may enrol after consultation with the Medical Monitor. Subjects with a positive RPR test who have not been treated may be rescreened at least 30 days after completion of antibiotic treatment for syphilis
* Subjects who, in the investigator's judgment, pose a significant suicide risk. Subject's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk
* The subject has a tattoo 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 DNA as follows:•Subjects positive for HBsAg are excluded;
* Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and 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; subjects who are anticipated to require HCV treatment within 12 months must be excluded. (HCV treatment on study may be permitted post Week 48, following consultation with the medical monitor) Subjects with HCV co-infection will be allowed entry into phase 3 studies if: Liver enzymes meet entry criteria; HCV Disease has undergone appropriate work-up, and is not advanced, and will not require treatment prior to the Week 48 visit. Additional information (where available) on subjects 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. In the event that recent biopsy or imaging data is not available or inconclusive, the Fib-4 score will be used to verify eligibility: Fib-4 score > 3.25 is exclusionary; Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation Fibrosis 4 Score Formula:( Age x AST ) / ( Platelets x ( sqr [ 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), 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 subject 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 subject 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 PK sampling, subjects 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 (=325mg).
* Any evidence of primary resistance based on the presence of any major known INI or NNRTI resistance-associated mutation, except for K103N, (International AIDS Society [IAS]-USA, 2015) 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 subject's participation in the study of an investigational compound
* Subject has estimated creatine clearance <50mL/min per 1.73m^2 via CKDEPI Method
* Alanine aminotransferase (ALT) =3 × 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. Note: Subjects using short term (e.g. =21 days) systemic corticosteroid treatment; topical, inhaled and intranasal corticosteroids are eligible for enrolment.
* 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
* Use of medications which are associated with Torsade de Pointes.
* Current or prior history of etravirine (ETR)
* Current use of tipranavir/ritonavir or fosamprenavir/ritonavir
* Subjects receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst, Sydney
Recruitment hospital [2] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [3] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [4] 0 0
GSK Investigational Site - Prahran
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2010 - Sydney
Recruitment postcode(s) [4] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Nebraska
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
Santa Fe
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Canada
State/province [23] 0 0
Saskatchewan
Country [24] 0 0
Canada
State/province [24] 0 0
Québec
Country [25] 0 0
France
State/province [25] 0 0
Montpellier Cedex 5
Country [26] 0 0
France
State/province [26] 0 0
Paris Cedex 10
Country [27] 0 0
France
State/province [27] 0 0
Paris Cedex 12
Country [28] 0 0
France
State/province [28] 0 0
Paris Cedex 13
Country [29] 0 0
France
State/province [29] 0 0
Paris
Country [30] 0 0
France
State/province [30] 0 0
Saint Denis Cedex 01
Country [31] 0 0
France
State/province [31] 0 0
Toulouse cedex 9
Country [32] 0 0
France
State/province [32] 0 0
Tourcoing cedex
Country [33] 0 0
Germany
State/province [33] 0 0
Bayern
Country [34] 0 0
Germany
State/province [34] 0 0
Hessen
Country [35] 0 0
Germany
State/province [35] 0 0
Niedersachsen
Country [36] 0 0
Germany
State/province [36] 0 0
Nordrhein-Westfalen
Country [37] 0 0
Germany
State/province [37] 0 0
Berlin
Country [38] 0 0
Germany
State/province [38] 0 0
Hamburg
Country [39] 0 0
Italy
State/province [39] 0 0
Lombardia
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Busan
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Daegu
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Daejeon
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Seoul
Country [44] 0 0
Mexico
State/province [44] 0 0
Jalisco
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Ekaterinburg
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Kazan
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Kemerovo
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Krasnodar
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Lipetsk
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Moscow
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Orel
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Saratov
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Smolensk
Country [54] 0 0
Russian Federation
State/province [54] 0 0
St. Petersburg
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Toliyatti
Country [56] 0 0
South Africa
State/province [56] 0 0
Free State
Country [57] 0 0
South Africa
State/province [57] 0 0
Gauteng
Country [58] 0 0
South Africa
State/province [58] 0 0
KwaZulu- Natal
Country [59] 0 0
South Africa
State/province [59] 0 0
Mpumalanga
Country [60] 0 0
South Africa
State/province [60] 0 0
Durban
Country [61] 0 0
South Africa
State/province [61] 0 0
Observatory, Cape Town
Country [62] 0 0
South Africa
State/province [62] 0 0
Pretoria
Country [63] 0 0
Spain
State/province [63] 0 0
Badalona
Country [64] 0 0
Spain
State/province [64] 0 0
Barcelona
Country [65] 0 0
Spain
State/province [65] 0 0
Córdoba
Country [66] 0 0
Spain
State/province [66] 0 0
Elche (Alicante)
Country [67] 0 0
Spain
State/province [67] 0 0
Madrid
Country [68] 0 0
Spain
State/province [68] 0 0
Malaga
Country [69] 0 0
Spain
State/province [69] 0 0
Santiago de Compostela
Country [70] 0 0
Spain
State/province [70] 0 0
Sevilla
Country [71] 0 0
Spain
State/province [71] 0 0
Valencia
Country [72] 0 0
Spain
State/province [72] 0 0
Vigo
Country [73] 0 0
Sweden
State/province [73] 0 0
Göteborg
Country [74] 0 0
Sweden
State/province [74] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ViiV Healthcare
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Janssen Pharmaceuticals
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
GlaxoSmithKline
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study is available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD is available via the Clinical Study Data Request site (click on the link provided below).
Available to whom?
Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://clinicalstudydatarequest.com/Posting.aspx?ID=20382


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.