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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

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ClinicalTrials.gov Identifier: NCT02951052
Recruitment Status : Active, not recruiting
First Posted : November 1, 2016
Results First Posted : June 13, 2019
Last Update Posted : November 19, 2019
Sponsor:
Collaborators:
Janssen Pharmaceuticals
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Tracking Information
First Submitted Date  ICMJE September 15, 2016
First Posted Date  ICMJE November 1, 2016
Results First Submitted Date  ICMJE May 23, 2019
Results First Posted Date  ICMJE June 13, 2019
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE October 28, 2016
Actual Primary Completion Date May 29, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2019)
Number of Participants With Virologic Failure (HIV-1 Ribonucleic Acid [RNA] >=50 Copies Per Millilter [mL]) Using Snapshot Algorithm at Week 48 [ Time Frame: Week 48 ]
Number of participants with virologic failure endpoint (HIV-1 RNA>=50 c/mL) as per Food and Drug Administration (FDA) snapshot algorithm at Week 48 was assessed to demonstrate the non-inferior antiviral activity of switching to intramuscular (IM) CAB LA+RPV LA every 4 weeks compared to continuation of current ART regimen over 48 weeks in HIV-1 infected ART-experienced participants. The HIV-1 RNA >=50 copies/mL per snapshot algorithm was determined by the last available on-treatment HIV-1 RNA measurement within the analysis visit window of interest.
Original Primary Outcome Measures  ICMJE
 (submitted: October 27, 2016)
Proportion of participants with plasma HIV 1 Ribonucleic acid <50 copies/millilitre (c/mL) at Week 48 [ Time Frame: Week (Wk) 48 ]
Proportion of participants with a virologic failure analyzed by Food and Drug Administration (FDA) Snapshot algorithm for the Intent-to-Treat Exposed population (subjects randomized and receiving at least one dose of investigational product during the Maintenance Phase)
Change History Complete list of historical versions of study NCT02951052 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2019)
  • Number of Participants With HIV-1 RNA <50 Copies/mL Using Snapshot Algorithm at Week 48 [ Time Frame: Week 48 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Number of participants with plasma HIV-1 RNA <50 copies/mL at Week 48 using FDA snapshot algorithm was assessed to demonstrate antiviral and immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to continuation of current ART. The HIV-1 RNA <50 copies/mL per snapshot algorithm was determined by the last available on-treatment HIV-1 RNA measurement within the analysis visit window of interest.
  • Number of Participants With HIV-1 RNA <200 Copies/mL Using Snapshot Algorithm at Week 48 [ Time Frame: Week 48 ]
    Number of participants with plasma HIV-1 RNA <200 copies/mL at Week 48 using the snapshot algorithm was assessed based on the antiviral and immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to continuation of current ART.
  • Number of Participants With Confirmed Virologic Failure (CVF) [ Time Frame: Weeks 8, 12, 20, 24, 32 and 40 ]
    The 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. The outcome displays only visits during which at least one new CVF occurs. Plasma samples were collected for quantitative analysis of HIV-1 RNA.
  • Absolute Values for Plasma HIV-1 RNA at Week 48 [ Time Frame: Week 48 ]
    Logarithm to base 10 (log10) values for plasma HIV-1 RNA has been presented.
  • Change From Baseline Values for Plasma HIV-1 RNA [ Time Frame: Baseline and Week 48 ]
    Plasma for quantitative HIV-1 RNA were collected at indicated time points. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as: HIV-1 RNA(log 10) at Week 48 - HIV-1 RNA(log 10) at Baseline.
  • Absolute Values for CD4+ Lymphocyte Count at Week 48 [ Time Frame: Week 48 ]
    Blood samples were collected and CD4+ cell count assessment by flow cyclometry was carried out to evaluate the immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to current ART.
  • Change From Baseline Values for CD4+ Lymphocyte Count at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood samples were collected and CD4+ cell count assessment by flow cyclometry was carried out to evaluate the immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to current ART.Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value at Week 48 minus Baseline value.
  • Number of Participants With Disease Progression [ Time Frame: Up to Week 48 ]
    Disease progression was defined as HIV-associated conditions, acquired immunodeficiency syndrome (AIDS), and death through 48 Weeks. Data of participants who experienced disease progression to Centers for Disease Control and Prevention (CDC) Stage III or death has been presented.
  • Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. Safety Population comprised of all randomized participants who received at least one dose of IP during the maintenance phase of the study (on or after Day 1 visit). Participants will be assessed according to actual treatment received.
  • Number of Participants With Severity of Adverse Events [ Time Frame: Up to Week 48 ]
    Severity of adverse events (AEs) were defined as per The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 2.0, November 2014. Severity grades for AEs were as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Potentially life-threatening) and Grade 5 were all deaths related to an AE.
  • Absolute Values for Hematology Parameters Over Time Including Week 48: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameters including basophil, eosinophils, leukocytes, lymphocytes, neutrophils, monocytes, and platelets at indicated time points.
  • Absolute Values for Hematology Parameters: Erythrocyte Mean Corpuscular Volume [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameter including erythrocyte mean corpuscular volume at indicated time points.
  • Absolute Values for Hematology Parameters: Erythrocytes [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameters including erythrocytes at indicated time points.
  • Absolute Values for Hematology Parameters: Hemoglobin [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated time points.
  • Absolute Values for Hematology Parameters: Hematocrit [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameters including hematocrit at indicated time points.
  • Change From Baseline for Hematology Parameters: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameters including basophil, eosinophils, leukocytes, lymphocytes, neutrophils, monocytes, and platelets at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline for Hematology Parameters: Erythrocyte Mean Corpuscular Volume [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameter including erythrocyte mean corpuscular volume at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline for Hematology Parameters: Erythrocytes [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameters including erythrocytes at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline for Hematology Parameters: Hematocrit [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameters including hematocrit at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline for Hematology Parameters: Hemoglobin [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatinine Kinase (CK) [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CK at indicated time points.
  • Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter-albumin at indicated time points.
  • Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin at indicated time points.
  • Absolute Values for Clinical Chemistry Parameters: Total Carbon-dioxide (CO2), Chloride, Glucose, Phosphate, Potassium, Sodium and Urea Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters which includes total CO2, chloride, glucose, phosphate, potassium, sodium and urea at indicated time points.
  • Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter-lipase at indicated time points.
  • Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter-creatinine clearance at indicated timepoints. Glomerular filtration rate (GFR) will be estimated by the central laboratory using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
  • Number of Participants With Abnormal Urinalysis Parameters Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 24 and 48. ]
    The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters (ketones, glucose, bilirubin, occult blood, nitrite and blood protein) can be read as positive, trace, 1+, 2+, 3+ and 4+ indicating proportional concentrations in the urine sample. The urine parameters were graded according to Division of AIDS (DAIDS) scale where Grade 1 indicates mild (trace to 1+), Grade 2 indicates moderate (2+) and Grade 3 indicates severe (3+ or higher). Only participants with abnormal findings for urinalysis at any visit has been presented.
  • Number of Participants With Urine Potential of Hydrogen (pH) Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 24 and 48 ]
    Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0).
  • Change From Baseline in Clinical Chemistry Parameters Over Time Including Week 48: ALT, ALP, AST and CK [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CK. Baseline values is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter-albumin. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters which includes total CO2, chloride, glucose, phosphate, potassium, sodium and urea. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter-lipase. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance. [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter-creatinine clearance. GFR will be estimated by the central laboratory using the CKD-EPI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Fasting Lipid Panel Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Week 48 ]
    Blood samples were collected for the analysis of fasting lipid parameters- total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 24 and 48 ]
    Urine biomarker samples were collected for the analysis of urine albumin/creatinine ratio and urine protein/creatinine ratio.Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values in Urine Creatinine Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 24 and 48 ]
    Urine biomarker samples were collected for the analysis of urine creatinine. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values in Urine Phosphate Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 24 and 48 ]
    Urine biomarker samples were collected for the analysis of urine phosphate. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values in Urine Retinol Binding Protein Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Week 48 ]
    Urine biomarker samples were collected for the analysis of urine retinol binding protein. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values in Urine Specific Gravity Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 24 and 48 ]
    Urine biomarker samples were collected for the analysis of urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The dipstick test gives results in a semi-quantitative manner. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. The urine specific gravity was measured as the ratio of urine density compared with water density.
  • Change From Baseline Values in Urine pH Over Time Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 24 and 48 ]
    Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). The dipstick test gives results in a semi-quantitative manner. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Number of Participants Who Discontinued or Withdrawn Due to AEs Over Time Including Week 48 [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
  • Percentage Change From Baseline in Fasting Lipids Overtime Including Week 48 [ Time Frame: Baseline (Day 1) and at Week 48 ]
    Blood samples were collected at Baseline and at Week 48 to assess fasting lipids which included total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Percentage change from Baseline is calculated as: value at Week 48 minus Baseline value divided by Baseline value multiplied by 100.
  • Number of Participants With Phenotypic Resistance Through Week 48 [ Time Frame: At the time of CVF ]
    Plasma samples were collected and analyzed from participants who met confirmed virologic withdrawal criteria.The CVF population comprised of all participants in ITT-E population who met CVF criteria.Phenotypic Resistance data for following drugs:CAB,dolutegravir(DTG),elvitegravir(EVG), raltegravir(RAL),delavirdine(DLV),efavirenz(EFV),etravirine(ETR),nevirapine(NVP),RPV,lamivudine(3TC),abacavir(ABC),emtricitabine(FTC),tenofovir(TDF),zidovudine(ZDV),stavudine(d4T),didanosine(ddI), atazanavir(ATV),darunavir(DRV),fosamprenavir(FPV),indinavir(IDV),lopinavir(LPV),nelfinavir(NFV),rito-navir(RTV),saquinavir(SQV) and tipranavir(TPV) in participants meeting CVF criteria is presented.Phenotypic resistance, partially sensitive, and Sensitive were defined based on fold change(FC) value from Monogram as:resistance(FC>clinical higher cutoff/biologic cutoff),partially sensitive(FC <=clinical higher cutoff and > clinical lower cutoff),sensitive(FC <= clinical lower cutoff/biologic cutoff).
  • Number of Participants With Genotypic Resistance Through Week 48 [ Time Frame: At the time of CVF ]
    Plasma samples were collected and analyzed from participants who met confirmed virologic withdrawal criteria. Genotypic Resistance data for the following drugs: DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV, DRV, FPV, IDV, LPV, NFV, RTV, SQV and TPV in participants meeting CVF criteria has been presented.
  • Number of Participants With AEs by Using Baseline Third Agent Treatment Class Overtime Including Week 48 [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
  • Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: ALT, ALP, AST and CK [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).
  • Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Albumin [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter: albumin to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).
  • Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Bilirubin, Direct Bilirubin and Creatinine [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter: bilirubin, direct bilirubin and creatinine to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).
  • Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Creatinine Clearance [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter: creatinine clearance to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). GFR will be estimated by the central laboratory using the CKD-EPI.
  • Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Lipase [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter: lipase to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).
  • Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters: CO2, chloride, glucose, phosphate, potassium, sodium and urea to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).
  • Absolute Values for Fasting Lipid Panel Using Baseline Third Agent Treatment Class Overtime Including Week 48 [ Time Frame: Baseline (Day 1) and at Week 48 ]
    Blood samples were collected for the analysis of fasting lipid panel: triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).
  • Number of Participants Discontinued or Withdrawn Due to AEs When Baseline Third Agent Treatment Class Was Used Over Time Including Week 48 [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
  • Plasma Trough Concentration (Ctrough) for CAB LA Evaluable [ Time Frame: Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples will be collected at indicated time points for pharmacokinetic (PK) analysis of CAB LA. PK population includes all participants who received CAB and / or RPV and underwent PK sampling during the study, and provided CAB and /or RPV plasma concentration data.
  • Ctrough for RPV LA Evaluable [ Time Frame: Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples will be collected at indicated time points for PK analysis of RPV LA.
  • Area Under the Curve (AUC) for CAB LA [ Time Frame: 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 ]
    AUC values are Bayesian PK parameter estimates obtained from a population PK meta-analysis of the data collected from studies 201585 and 201584 # NCT02938520. Blood samples from the current study 201585 were collected at indicated time points to analyze concentration in plasma for CAB LA.
  • AUC for RPV LA [ Time Frame: 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 ]
    AUC values are Bayesian PK parameter estimates obtained from a population PK meta-analysis of the data collected from studies 201585 and 201584 # NCT02938520. Blood samples from the current study 201585 were collected at indicated time points to analyze concentration in plasma for RPV LA.
  • Maximum Concentration (Cmax) in Plasma for CAB LA Evaluable at Week 41 [ Time Frame: Week 41- 1 Week post dose ]
    Blood samples will be collected at indicated time points for PK analysis of CAB LA.
  • Cmax in Plasma for RPV LA Evaluable at Week 41 [ Time Frame: Week 41- 1 Week post dose ]
    Blood samples will be collected at indicated time points for PK analysis of RPV LA.
  • Percentage of Participants With a Virologic Failure Using Snapshot Algorithm by Baseline Third Agent [ Time Frame: Week 48 ]
    Percentage of participants with virologic failure endpoint as per FDA snapshot algorithm at Week 48 was assessed based on the non-inferior antiviral activity of switching IM CAB LA+RPV LA every 4 weeks compared to continuation of current ART regimen over 48 weeks in HIV-1 infected ART-experienced participants. The HIV-RNA >=50 copies/mL per snapshot algorithm was determined using a Cochran-Mantel Haenszel test stratified by baseline third agent class: INI, NNRTI, or PI.
  • Percentage of Participants With Plasma HIV-1 RNA <50copies/mL Using Snapshot Algorithm by Baseline Third Agent [ Time Frame: Week 48 ]
    Percentage of participants with HIV-1 RNA < 50copies/mL endpoint as per FDA snapshot algorithm at Week 48 was assessed based on the non-inferior antiviral activity of switching IM CAB LA+RPV LA every 4 weeks compared to continuation of current ART regimen over 48 weeks in HIV-1 infected ART-experienced participants. The HIV-RNA <50 copies/mL per snapshot algorithm was determined using a Cochran-Mantel Haenszel test stratified by baseline third agent class: INI, NNRTI, or PI.
  • Number of Participants With Severity of Adverse Events by Baseline Third Agents [ Time Frame: Up to Week 48 ]
    Severity of AEs were defined as per The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table). Severity grades for AEs were as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Potentially life-threatening) and Grade 5 were all deaths related to an AE.
  • Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: ALT, ALP, AST and CK [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters: ALT, ALP, AST and CK to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Albumin [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter: albumin to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Bilirubin, Direct Bilirubin and Creatinine [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter: bilirubin, direct bilirubin and creatinine to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Creatinine Clearance [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter: creatinine clearance to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). GFR will be estimated by the central laboratory using the CKD-EPI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Lipase [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameter: lipase to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48 [ Time Frame: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ]
    Blood samples were collected for the analysis of clinical chemistry parameters: CO2, chloride, glucose, phosphate, potassium, sodium and urea to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline Values for Fasting Lipid Panel Using Baseline Third Agent Treatment Class Overtime Including Week 48 [ Time Frame: Baseline (Day 1) and at Week 48 ]
    Blood samples were collected for the analysis of fasting lipid panel: triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Number of Participants With Genotypic Resistance Using Baseline Third Agent Through Week 48 [ Time Frame: At the time of CVF ]
    Plasma samples were collected from participants who met confirmed virologic withdrawal criteria to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Genotypic Resistance data for the following drugs: DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV, DRV, FPV, IDV, LPV, NFV, RTV, SQV and TPV in participants meeting CVF criteria has been presented.
  • Number of Participants With Phenotypic Resistance Using Baseline Third Agent Through Week 48 [ Time Frame: At the time of CVF ]
    Plasma samples were collected from participants who met confirmed virologic withdrawal criteria to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Phenotypic Resistance data for the following drugs: CAB, DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV, DRV, FPV, IDV, LPV, NFV, RTV, SQV and TPV in participants meeting CVF criteria has been presented. Phenotypic resistance, partially sensitive, and Sensitive were defined based on FC value from Monogram as: resistance (FC>clinical higher cutoff/biologic cutoff), partially sensitive (FC <=clinical higher cutoff and > clinical lower cutoff), sensitive (FC <= clinical lower cutoff/biologic cutoff).
  • Change From Week 5 in Dimension Scores Using Percerption of Injection Questionnaire (PIN)-Last Observation Carried Forward (LOCF) in Q4W Arm [ Time Frame: Week 5 and at Weeks 41 and 48 ]
    The PIN questionnaire explores the bother of pain at the injection site and injection site reactions (ISR), 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.Scores range from 1 to 5, and questions are phrased in such a way as to ensure that 1 always equated with the most favourable perception of vaccination, and 5 the most unfavourable.Dimension scores include bother from ISR, leg movement, sleep and acceptability.The score of a domain is calculated as the mean of all items with the domain.Higher scores represent worse perception of injection. LOCFwas used as primary method of analysis
  • Percentage of Participants With Extremely or Very Acceptable Pain and Local Reaction: Acceptability Score on PIN Questionnaire in Q4W Arm [ Time Frame: Weeks 5, 41 and 48 ]
    The PIN questionnaire explores the bother of pain at the injection site and injection site reactions(ISR), 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.Scores range from 1 to 5, and questions are phrased in such a way as to ensure that 1 always equated with the most favourable perception of vaccination, and 5 the most unfavourable.Dimension scores include bother from ISR, leg movement, sleep and acceptability.The score of a domain is calculated as the mean of all items with the domain.Higher scores represent worse perception of injection. LOCF was used as primary method of analysis
  • Change From Baseline in Life Satisfaction (LISAT) Using HIV/AIDs-targeted Quality of Life (HATQoL) Questionnaire [ Time Frame: Baseline (Day 1) and at Weeks 24 and 48 ]
    The HATQoL questionnaire was used to assess the health related QoL (HRQoL). It comprises of three dimensions: LISAT, medication worries (MEDWO) and disclosure worries (DISWO). The total imputed value score for LISAT is calculated on a 0-100 scale using the formula: LISAT 100=[100 divided by (20 minus 4)]*(LISAT minus 4). A response of 5 in LISAT score shows satisfaction all of the time and 1 as none of the time. The higher the score, the greater satisfaction to life and the less worry. The transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Measure type was considered as mean for adjusted mean and dispersion measure as 95% confidence interval (CI).Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline in HIV Medication, MEDWO Using HATQoL [ Time Frame: Baseline and at Weeks 24 and 48 ]
    The HATQoL questionnaire was used to assess the health related QoL (HRQoL). It comprises of three dimensions: LISAT, medication worries (MEDWO) and disclosure worries (DISWO). The total imputed value score for MEDWO is calculated on a 0-100 scale using the formula: MEDWO 100=[100 divided by (20 minus 5)]*(MEDWO minus 5). A response of 1 in MEDWO score shows less medication worries all of the time and 5 as none of the time. The higher the score, the greater satisfaction to life and the less worry. The transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline in DISWO Using HATQoL [ Time Frame: Baseline and at Weeks 24 and 48 ]
    The HATQoL questionnaire was used to assess the health related QoL (HRQoL). It comprises of three dimensions: LISAT, medication worries (MEDWO) and disclosure worries (DISWO). The total imputed value score for DISWO is calculated on a 0-100 scale using the formula: DISWO 100=[100 divided by (20 minus 5)]*(DISWO minus 5). A response of 1 in DISWO score shows less medication worries all of the time and 5 as none of the time. The higher the score, the greater satisfaction to life and the less worry. The transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline in Health Status Using 12-item Short Form Survey (SF-12) [ Time Frame: Baseline and at Weeks 24 and 48 ]
    The SF-12 questionnaire consists of 7 questions which measures the degree of general health status and mental health distress. Each question is scored 0-5, except for question 2 scored 0-3. The HRQoL using SF-12 for the total score, physical component summary (PCS) and the mental component summary (MCS) were assessed for the two treatment groups. Missing Total or the component scores was imputed using LOCF. The PCS/MCS are calculated using computer software purchased from QualityMetric (http://www.qualitymetric.com). The higher the score, the better will be the health status. Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Change From Baseline in Total Treatment Satisfaction Using HIV Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4b, 24 and 44 [ Time Frame: Baseline and at Weeks 4b, 24 and 44 ]
    The HIVTSQ for total treatment satisfaction score is computed with 1-11 items. These 1-11 items are summed to produce a score with a possible range of -33 to 33. The item 12 in the scale will be calculated as an individual score.The higher the score, the greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment.A score of 0 represents no change. A maximum of 5 items can be missing, the missing scores will be imputed with the mean of the completed item scores. If 6 or more items are missing, then the overall treatment satisfaction scale score should not be computed and will remain missing.LOCF was used as primary method of analysis. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. Data has been presented with respect to actual treatment received to the participants
  • Change in Treatment Satisfaction Over Time Using HIVTSQ Change (HIVTSQc) at Week 48 in Q4W Arm [ Time Frame: Week 48 ]
    The HIVTSQ for total treatment satisfaction score is computed with 1-11 items. These 1-11 items are summed to produce a score with a possible range of -33 to 33. The item 12 in the scale will be calculated as an individual score.The higher the score, the greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment.A score of 0 represents no change. A maximum of 5 items can be missing, the missing scores will be imputed with the mean of the completed item scores. If 6 or more items are missing, then the overall treatment satisfaction scale score should not be computed and will remain missing.LOCF was used as primary method of analysis. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. Data has been presented with respect to actual treatment received to the participants
  • Change From Baseline in Treatment Acceptance at Weeks 8, 24 and 48 Using "General Acceptance" Dimension of the Chronic Treatment Acceptance (ACCEPT) Questionnaire [ Time Frame: Baseline and at Weeks 8, 24 and 48 ]
    The ACCEPT questionnaire is a generic medication acceptance measure assessing how participants weigh advantages and disadvantages of long-term medication.The questionnaire consists of 25 items that capture six dimensions.3 questions that focus on general acceptance of study medication will be analyzed.Items on the scale are rated as 1-5 scores:1:totally disagree,2:somewhat disagree,3:somewhat agree, 4:totally agree and 5:I don't know.Total score of the dimension is calculated as the mean of the recoded items of the dimension and then linearly transformed to be on a scale from 0 to 100:score:Total Score=(mean of the recoded items in the dimension minus1)divided by2*100.LOCF was used as primary method of analysis.Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI.Baseline value is defined as the latest pre-treatment assessment with a non-missing value.Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value
  • Change From 4b in Tolerability of Injection at Week 5, 40 and 41 Using Numeric Rating Scale (NRS) Within CAB LA+RPV LA Arm [ Time Frame: Weeks 4b, 5, 40 and 41 ]
    The NRS questionnaire is used to assess the tolerability of injections in CAB LA+RPV LA arm only. The questionnaire consists of one single question and will assess maximum level of pain experienced with the most recent injections ranking from no pain (0) to extreme pain (10). Missing scores was imputed using LOCF.
  • Change From Baseline in Individual Item Scores of HIVTSQc at Weeks 4b, 24 and 44 [ Time Frame: Baseline and Weeks 4b, 24 and 44 ]
    HIVTSQc is a 12 item questionnaire. The individual treatment change item scores on HIVTSQc scale are rated as +3 ('much more satisfied', 'much more convenient', 'much more flexible',etc.) to -3 ('much less satisfied', 'much less convenient', 'much less flexible', etc.). The higher the score, the greater the improvement in satisfaction with each aspect of treatment and the lower the score, the greater the deterioration in satisfaction with each aspect of treatment. LOCF was used as primary method of analysis. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.
  • Number of Participants With Different Demographic Parameters for Inter-subject Variability [ Time Frame: Upto Week 48 ]
    Blood samples were planned to be collected at indicated time points for PK analysis of CAB LA and RPV LA. Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters were planned to be evaluated as potential predictors of inter subject variability for pharmacokinetic parameters.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 27, 2016)
  • Proportion of participants with Plasma HIV-1 RNA <50 copies/mL (c/mL) [ Time Frame: Up to week 96 ]
    Assessed using the FDA Snapshot algorithm at week 48 and week 96. It is a key secondary endpoint
  • Proportion of participants with plasma HIV-1 RNA <200 c/mL [ Time Frame: Up to week 96 ]
    Assessed using the FDA Snapshot algorithm at week 48 and week 96
  • Proportion of participants with confirmed virologic failure [ Time Frame: Up to week 96 ]
    Two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to <200 c/mL. Assessed at week 48 and week 96
  • CHANGE FROM BASELINE IN PLASMA HIV-1 RNA [ Time Frame: Baseline and up to week 96 ]
    Analyzed at week 48 and week 96
  • CHANGES FROM BASELINE IN CD4+ CELL COUNTS [ Time Frame: Baseline and up to week 96 ]
    Analyzed at week 48 and week 96
  • INCIDENCE OF DISEASE PROGRESSION [ Time Frame: Up to week 96 ]
    Assessed by HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death at week 48 and week 96
  • Incidence and severity of adverse events (AEs) [ Time Frame: Up to Wk 96 ]
    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 judgement will be categorized as serious adverse event (SAE). Incidence and severity will be analyzed at Week 48 and week 96
  • Incidence and severity of laboratory abnormalities [ Time Frame: Up to Wk 96 ]
    Incidence and severity will be analyzed at Week 48 and Week 96
  • Proportion of participants who discontinue treatment due to AEs [ Time Frame: Up to Wk 96 ]
    Participants who discontinue treatment due to AEs at Week 48 and Week 96 will be analyzed
  • Number of participants having changes in laboratory parameters [ Time Frame: Baseline and up to Wk 96 ]
    Laboratory parameters includes; 1. Hematology parameters-platelet count, red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular volume, WBC differential (includes; neutrophils, lymphocytes, monocytes, eosinophils and basophils), 2. Clinical chemistry- blood urea nitrogen, creatinine, fasting glucose, sodium, potassium, chloride, total carbon dioxide, lipase, aspartate aminotransferase , alanine aminotransferase, alkaline phosphatase, phosphate, total bilirubin, albumin, creatine phosphokinase, creatinine clearance will be analyzed over Week 48 and Week 96
  • Incidence of treatment emergent resistance [ Time Frame: Baseline and up to Wk 96 ]
    Genotypic and phenotypic resistance to CAB, RPV, and other on-study antiretroviral treatment (ART) at Week 48 and Week 96
  • PLASMA TROUGH CONCENTRATION (CTROUGH) FOR CAB LA [ Time Frame: Wk 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and 96 for intramuscular arm (IM)and Wk 60 for participants transitioning to IM arm ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at , 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 96 in intramuscular (IM) arm and at Wk 60 for participants transitioning to CAB LA + RPV LA from ART group
  • Plasma trough concentration (Ctrough) for RPV LA [ Time Frame: Wk 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and 96 for intramuscular arm (IM)and Wk 60 for participants transitioning to IM arm ]
    Blood sample will be obtained from Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at , 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 96 in intramuscular (IM) arm and at Wk 60 for participants transitioning to CAB LA + RPV LA from ART group
  • Maximum concentration (Cmax) in plasma for CAB LA arm [ Time Frame: Wk 5 and Wk 41 ]
    Blood sample will be obtained from participants at Post-dose
  • Maximum concentration (Cmax) in plasma for RPV LA arm [ Time Frame: Wk 5 and Wk 41 ]
    Blood sample will be obtained from participants at Post-dose
  • PLASMA AREA UNDER THE CONCENTRATION-TIME CURVE (AUC) FOR CAB LA [ Time Frame: Wk 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, and 96 ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 96 in IM arm. Post-dose sample will be collected at Wk 5, Wk 41
  • PLASMA AREA UNDER THE CONCENTRATION-TIME CURVE (AUC) FOR RPV LA [ Time Frame: Wk 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, and 96 ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 96 in IM arm. Post-dose sample will be collected at Wk 5, Wk 41
  • Proportion of participants with a virologic failure analyzed by FDA Snapshot algorithm [ Time Frame: Wk 96 ]
    As per FDA Snapshot algorithm virological failure will be determined on the basis of participants who missed, switched or discontinued the treatment
  • Acceptance of injection-related pain and injection site reactions (ISRs) (for CAB LA + RPV LA) [ Time Frame: Week 4 to Week 96 ]
    The Perception of iNjection questionnaire (PIN) will be used to assess the following dimension scores: Bother of ISRs, Leg movement, Sleep, and Injection Acceptance. Additionally, individual PIN item scores will 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. PIN will be assessed at weeks 5, 41, 48, 96 and/or With drawal .Key secondary endpoints include the proportion of participants considering pain and local reactions following injection to be extremely or very acceptable based on the acceptability score after first injection and over time, and changes in the PIN acceptance score within the CAB LA + RPV LA arm over time
  • Change from baseline in health related quality of life (HAT-Qol) [ Time Frame: Baseline to Wk 96 ]
    HR QoL will be assessed in Day 1 and Week 24, Week 48, Week 96
  • Change from baseline in treatment satisfaction [ Time Frame: Baseline and up to Wk 96 ]
    The HIV Treatment Satisfaction Questionnaire-status-12 (HIVTSQs-12) will be used to assess the "Total Treatment Satisfaction" score as well as the following sub-scale scores: "pain/discomfort" and "ease of administration. HIVTSQs-12 will be assessed at Baseline (Day 1) and weeks 4b, 24, 44, 96 and/or WD. The change from baseline in HIVTSQs total score at Week 44 is a key secondary endpoint
  • Change from previous therapy in treatment satisfaction [ Time Frame: Baseline up to Week 48 ]
    The HIV Treatment Satisfaction Questionnaire-change-12 (HIVTSQc-12) will be used to assess the "Total Treatment Satisfaction" score as well as the following sub-scale scores: "pain/discomfort" and "ease of administration. It will assessed at week 96 and/or WD
  • Change in health status [ Time Frame: Baseline to Wk 96 ]
    Overall health status will be assessed with the 12-item Short Form Health Survey (SF-12) as well as the Physical and Mental Health component scores. SF-12 will be assessed at Baseline (Day 1) and weeks 24, 48, 96 and/or WD
  • Change in treatment acceptance [ Time Frame: Baseline to Wk 96 ]
    Overall treatment acceptance to chronic therapy will be assessed with 3 items from the ACCEPT questionnaire. It will be assessed at Baseline (Day 1) and weeks 8, 24, 48, 96 and/or WD
  • Change in tolerability of injection from Week 4b, Week 5, Week 40, Week 41, and Week 96. [ Time Frame: Baseline to Wk 96 ]
    Patient reported injection tolerability will be assessed in subjects receiving CAB LA + RPV LA using a single item 11-point Likert-based numeric rating scale (NRS) administered 30-60 minutes following the injections. NRS will be assessed at weeks 4b, 5, 40, 41, and 96
  • Pre-dose concentrations of CAB and RPV in all participants randomized to CAB LA and RPV LA. [ Time Frame: Pre-dose blood samples will be collected Week 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100, 108, Withdrawal for analysis of CAB and RPV PK ]
    CAB and RPV trough concentrations and AUC will be determined in participants switching to CAB + RPV.
  • 2 Hours Post Dose concentrations of CAB and RPV in all participants randomized to CAB LA and RPV LA [ Time Frame: Week 4b, Week 48, Week 96 for analysis of CAB and RPV PK ]
    CAB and RPV concentrations immediately following injection with CAB LA and RPV LA will be determined in participants switching to CAB + RPV.
  • 1 Week Post Dose concentration of CAB and RPV in all participants randomized to CAB LA and RPV LA [ Time Frame: Week 5 and Week 41 for analysis of CAB and RPV PK ]
    CAB and RPV Cmax concentrations will be determined in participants switching to CAB + RPV.
  • Pre-Dose concentration for all participants switching to CAB + RPV from ABC/DTG/3TC [ Time Frame: Week 104b, 108, Withdrawal for analysis of CAB and RPV PK ]
    CAB and RPV trough concentrations will be determined in participants switching to CAB + RPV.
  • 2 Hour Post-Dose concentration for all participants switching to CAB + RPV from ABC/DTG/3TC [ Time Frame: Week 104b for analysis of CAB and RPV PK ]
    CAB and RPV concentrations immediately following injection with CAB LA and RPV LA will be determined in participants switching to CAB + RPV.
  • PK-pharmacodynamic (PD) assessment for CAB LA and RPV LA [ Time Frame: Up to Week 96 ]
    The PK-PD relationship will be explored between plasma PK parameters and plasma HIV-1 RNA, CD4+ cell counts and/or occurrence of AEs through Week 96 of the Maintenance Period.
  • Exposure-response relationship for CAB LA and RPV LA [ Time Frame: Up to Week 96 ]
    The exposure-response relationship will be explored between plasma PK parameters and age, sex, race, body weight, body mass index, and relevant laboratory parameters through Week 96 of the Maintenance Period.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary The Antiretroviral Therapy as Long Acting Suppression (ATLAS) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult subjects with current viral suppression on a regimen with 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent, remain suppressed upon switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). This is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, antiretroviral therapy (ART)-adult subjects who are stably suppressed on a current antiretroviral (ARV) regimen. This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks (Q4W: monthly) compared with maintenance of current ARV regimen containing 2 NRTIs plus an INI, NNRTI, or a PI. Eligible subjects will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue current ART or switch to initiate oral therapy with CAB 30 mg + RPV 25 mg once daily for 4 Weeks followed by Q4 weekly (monthly) CAB LA + RPV LA injections. Following the Maintenance phase at Week 52, subjects who were randomized to continue their current ART regimen will be given an option to switch to CAB LA + RPV LA injections. Those subjects would transition to LA dosing, beginning with 4 weeks oral CAB + RPV therapy at Week 52, and receive the first IM CAB LA + RPV LA injections at Week 56.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Infection, Human Immunodeficiency Virus
  • HIV Infections
Intervention  ICMJE
  • Drug: 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
  • Drug: 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
  • Drug: 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
  • Drug: 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.
  • Drug: 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)
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Cabotegravir (CAB) tablet
    • Drug: Rilpivirine (RPV) tablet
    • Drug: Cabotegravir - Injectable Suspension (CAB LA)
    • Drug: Rilpivirine - Injectable Suspension (RPV LA)
  • 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.
    Intervention: Drug: 2 NRTIs plus an INI, NNRTI, or PI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 10, 2018)
618
Original Estimated Enrollment  ICMJE
 (submitted: October 27, 2016)
570
Estimated Study Completion Date  ICMJE February 8, 2022
Actual Primary Completion Date May 29, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Canada,   France,   Germany,   Italy,   Korea, Republic of,   Mexico,   Russian Federation,   South Africa,   Spain,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02951052
Other Study ID Numbers  ICMJE 201585
2016-001647-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: 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.
URL: http://clinicalstudydatarequest.com
Responsible Party ViiV Healthcare
Study Sponsor  ICMJE ViiV Healthcare
Collaborators  ICMJE
  • Janssen Pharmaceuticals
  • GlaxoSmithKline
Investigators  ICMJE
Study Director: GSK Clinical Trials ViiV Healthcare
PRS Account ViiV Healthcare
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP