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Phase 2b, Open-label, Multicenter, Rollover Study to Assess Antiviral Activity and Safety of Long-acting (LA) Cabotegravir (CAB) Plus LA Rilpivirine (RPV), Administered Every 2 Months (Q2M), in Human Immunodeficiency Virus (HIV)-Positive Participants From the LATTE Study

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ClinicalTrials.gov Identifier: NCT03639311
Recruitment Status : Active, not recruiting
First Posted : August 21, 2018
Results First Posted : January 15, 2021
Last Update Posted : March 22, 2021
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
ViiV Healthcare

Tracking Information
First Submitted Date  ICMJE August 10, 2018
First Posted Date  ICMJE August 21, 2018
Results First Submitted Date  ICMJE November 20, 2020
Results First Posted Date  ICMJE January 15, 2021
Last Update Posted Date March 22, 2021
Actual Study Start Date  ICMJE August 20, 2018
Actual Primary Completion Date December 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2020)
Percentage of Participants With HIV-ribonucleic Acid (RNA) >=50 Copies Per Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Algorithm at Month 12 [ Time Frame: Month 12 ]
Percentage of participants with HIV-1 RNA >=50 c/mL as per FDA snapshot algorithm at Month 12 was assessed to demonstrate the antiviral activity of CAB LA+RPV LA Q2M and DTG + RPV regimen in HIV-1 infected antiretroviral therapy (ART) experienced participants. The HIV-1 RNA >=50 c/mL per Snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the 12 months analysis visit window. Intent-to-treat-Exposed (ITT-E) Population comprised of all participants who received at least one dose of investigational product (IP) during on or after Day 1 visit. Participants were analyzed according to the selected treatment regardless of what treatment was actually received.
Original Primary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
Number of subjects with HIV-RNA >=50 c per mL as per food and drug administration (FDA) Snapshot algorithm at Month 12 [ Time Frame: Month 12 ]
Plasma samples will be collected from the subject at specific time points. The Abbott RealTime HIV-1 Assay lower limit of detection (LLOD) 40 c/mL, will be used.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2021)
  • Percentage of Participants With HIV-RNA <50 c/mL as Per FDA Snapshot Algorithm at Month 12 [ Time Frame: Month 12 ]
    Percentage of participants with HIV-1 RNA <50 c/mL as per FDA snapshot algorithm at Month 12 was assessed to demonstrate the antiviral activity of CAB LA+RPV LA Q2M and oral DTG + RPV regimen. The HIV-1 RNA <50 c/mL per Snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the 12 months analysis visit window.
  • Percentage of Participants With Protocol-defined Confirmed Virologic Failure Overtime [ Time Frame: Up to Month 12 ]
    Confirmed virologic failure was defined as rebound as indicated by two consecutive plasma HIV-1-RNA levels >=200 c/mL after prior suppression to <200 c/mL.
  • Percentage of Participants With HIV-RNA >=50 c/mL as Per FDA Snapshot Algorithm Over Time for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 6, 8, 10 and 12 ]
    Percentage of participants with HIV-1 RNA >=50 c/mL as per FDA snapshot algorithm over time was assessed to demonstrate the antiviral activity of CAB LA+RPV LA Q2M regimen in HIV-1 infected ART experienced participants. The HIV-1 RNA >=50 c/mL per Snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the 12 months analysis visit window. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
  • Percentage of Participants With HIV-RNA >=50 c/mL as Per FDA Snapshot Algorithm Over Time for DTG + RPV [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Percentage of participants with HIV-1 RNA >=50 c/mL as per FDA snapshot algorithm over time was assessed to demonstrate the antiviral activity of DTG + RPV regimen in HIV-1 infected ART experienced participants. The HIV-1 RNA >=50 c/mL per Snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the 12 months analysis visit window. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
  • Absolute Values for HIV-1 RNA of CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 6, 8, 10 and 12 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log10) values for plasma HIV-1 RNA have been presented. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
  • Absolute Values for HIV-1 RNA of DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log10) values for plasma HIV-1 RNA has been presented. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
  • Change From Baseline in HIV-1 RNA for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 6, 8, 10 and 12 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Log 10 values for plasma HIV-1 RNA has been presented. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
  • Change From Baseline in HIV-1 RNA for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Log 10 values for plasma HIV-1 RNA has been presented. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
  • Absolute Values for Cluster of Differentiation 4 Plus (CD4+) for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 6, 8, and 12 ]
    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunologic activity of CAB LA+RPV LA Q2M. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
  • Absolute Values for CD4+ for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunologic activity of DTG + RPV arm. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
  • Change From Baseline Values for CD4+ for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 6, 8, and 12 ]
    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunologic activity of CAB LA+RPV LA Q2M. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
  • Change From Baseline Values for CD4+ for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunologic activity of DTG + RPV arm. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
  • Number of Participants With Non-serious Adverse Events (Non-SAEs >=5 Percent [%] Incidence) and Serious Adverse Events (SAEs) [ Time Frame: Up to Month 17 ]
    An adverse event 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 participants who received at least one dose of study treatment on or after Day 1 visit. Participants were assessed according to actual treatment received.
  • Number of Participants With Severity of Adverse Events [ Time Frame: Up to Month 17 ]
    Severity of adverse events were defined as per The Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS adverse events Grading Table). Severity grades for adverse events were Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Potentially life-threatening) and Grade 5 (all deaths related to an AE).
  • Number of Participants With Maximum Post-Baseline Chemistry Toxicities [ Time Frame: Up to Month 12 ]
    Clinical chemistry toxicities were graded as per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table). Blood samples were collected for the analysis of following clinical chemistry parameters: alanine aminotransferase (ALT), albumin, aspartate aminotranferase (AST), bilirubin, carbon dioxide (CO2), cholesterol, creatinine kinase, creatinine, direct bilirubin, glomerular filtration rate (GFR) from creatinine adjusted using chronic kidney disease epidemiology collaboration (CKD-EPI), GFR from creatinine adjusted for bovine serum albumin (BSA), glucose, low density lipoprotein (LDL) cholesterol calculation, lipase, phosphate, sodium and triglycerides. Severity grades were: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening).
  • Number of Participants With Maximum Post-Baseline Hematology Toxicities [ Time Frame: Up to Month 12 ]
    The hematology toxicities were graded as per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table). Blood samples were collected for the analysis of following hematology parameter: platelets. Severity grades were: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening).
  • Percentage of Participants Who Permanently Discontinued Treatment Due to Adverse Events [ Time Frame: Up to Month 12 ]
    An adverse event 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 of participants with adverse events leading to permanent withdrawal has been presented.
  • Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatinine Kinase Over Time for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameters including ALT, ALP, AST and creatinine kinase. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and Creatinine Kinase Over Time for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameters including ALT, ALP, AST and creatinine kinase. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameter: Albumin Over Time for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameter: albumin. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameter: Albumin Over Time for DTG+ RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameter: albumin. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine Over Time for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameters: bilirubin and creatinine. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine Over Time for DTG+ RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameters: bilirubin and creatinine. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameters: Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea Over Time for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameters: carbon dioxide, chloride, glucose, phosphate, potassium, sodium and urea. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameters: Carbon Dioxide, Chloride, Glucose, Phosphate, Potassium, Sodium and Urea Over Time for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameters: carbon dioxide, chloride, glucose, phosphate, potassium, sodium and urea. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameters: Cholesterol, High Density Lipoprotein (HDL) Cholesterol Direct, Low Density Lipoprotein (LDL) Cholesterol Calculation, LDL Cholesterol Direct and Triglycerides for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Month 12 ]
    Blood samples were collected for the analysis of clinical chemical parameters: cholesterol, direct HDL cholesterol, LDL cholesterol calculation, direct LDL cholesterol and triglycerides. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Absolute Values of Clinical Chemistry Parameters: Cholesterol, Direct HDL Cholesterol, LDL Calculation, Direct LDL Cholesterol and Triglycerides for DTG + RPV Arm [ Time Frame: At Day 1 ]
    Blood samples were collected for the analysis of clinical chemical parameters: cholesterol, HDL cholesterol direct, LDL cholesterol calculation, LDL cholesterol direct and triglycerides.
  • Change From Baseline in Clinical Chemistry Parameter: GFR From Creatinine Adjusted Using CKD-EPI for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameter: GFR from creatinine adjusted using CKD-EPI. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameter: GFR From Creatinine Adjusted Using CKD-EPI for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameter: GFR from creatinine adjusted using CKD-EPI. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameter: GFR From Creatinine Adjusted BSA for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameter: GFR from creatinine adjusted for BSA. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameter: GFR From Creatinine Adjusted BSA for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameter: GFR from creatinine adjusted for BSA. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameter: Lipase for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameter: lipase. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameter: Lipase for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of clinical chemical parameter: lipase. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameter: Total Cholesterol/ HDL Cholesterol Ratio for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Month 12 ]
    Blood samples were collected for the analysis of clinical chemical parameter: total cholesterol/ HDL cholesterol ratio. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Clinical Chemistry Parameter: Total Cholesterol/ HDL Cholesterol Ratio for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Month 6 ]
    Blood samples were collected for the analysis of clinical chemical parameter: total cholesterol/ HDL cholesterol ratio. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of hematology parameter: erythrocytes mean corpuscular volume. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of hematology parameter: erythrocytes mean corpuscular volume. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameter: Erythrocytes for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of hematology parameter: erythrocytes. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameter: Erythrocytes for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of hematology parameter: erythrocytes. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameter: Hematocrit for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameter: Hematocrit for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameter: Hemoglobin for CAB LA + RPV LA Q2M Arm [ Time Frame: Baseline (Day 1) and at Months 2, 4, 8 and 12 ]
    Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Hematology Parameter: Hemoglobin for DTG + RPV Arm [ Time Frame: Baseline (Day 1) and at Months 3, 6, 9 and 12 ]
    Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio [ Time Frame: At Day 1 ]
    Urine samples were collected for the analysis of urine albumin/creatinine ratio and urine protein/creatinine ratio.
  • Absolute Values of Urine Creatinine [ Time Frame: At Day 1 ]
    Urine samples were collected for the analysis of urine creatinine.
  • Absolute Values of Urine Phosphate [ Time Frame: At Day 1 ]
    Urine samples were collected for the analysis of urine phosphate.
  • Absolute Values of Urine Specific Gravity [ Time Frame: At Day 1 ]
    Urine 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.
  • Absolute Values of Urine Potential of Hydrogen (pH) [ Time Frame: At Day 1 ]
    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).
  • Number of Participants With Treatment Emergent Genotypic Resistance [ Time Frame: Up to Month 12 ]
    Plasma samples were collected and analyzed for genotypic resistance from participants who met confirmed virologic withdrawal criteria.
  • Number of Participants With Treatment Emergent Phenotypic Resistance [ Time Frame: Up to Month 12 ]
    Plasma samples were collected and analyzed from participants who met confirmed virologic withdrawal criteria.
  • Change From Baseline in HIV Dependent Quality of Life (HIVDQoL - Self-completion Questionnaire Designed to Measure QoL in People Living With HIV) [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
    HIVDQoL includes 2 overview items and 26 domain items. The 2 overview items: Item 1: 3(excellent) to -3(extremely bad); Higher score indicates better quality of life. Item 2: -3(very much better) to 1(worse); Lower score indicates better quality of life. The Weighted impact score was calculated for 26 individual domain items by multiplying impact score (-3[maximum negative impact] to +1[maximum positive impact] by the corresponding importance score (3 [very important] to 0[not all important]). Average Weighted impact (AWI) score was calculated by summing individual weighted impact scores and dividing by the number of domain items. The ranges of weighted impact score and average impact score were from -9(maximum negative impact) to +3(maximum positive impact); higher score indicates positive impact. Change from Baseline was defined as post-dose visit value minus Baseline value (latest pre-treatment assessment with a non-missing value).
  • Change From Baseline in Treatment Satisfaction Score of HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
    HIVTSQs total treatment satisfaction score is computed with 1-11 items. Items 1-11 are summed to produce score with possible range of 0 to 66. Higher the score, greater improvement in satisfaction with treatment; lower score, greater the deterioration in satisfaction with treatment. A score of 0 represents no change. The higher the score, the greater the improvement in treatment satisfaction as compared to the past few weeks. A smaller score represents a decline in treatment satisfaction compared to the past few weeks. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
  • Change From Baseline in Individual Item Score of HIVTSQs [ Time Frame: Baseline (Day 1) and at Months 6 and 12 ]
    HIVTSQs is a 12 item questionnaire. The individual item scores are rated as 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater treatment satisfaction as compared to the past few weeks. Change from Baseline is defined as post-dose value minus Baseline value. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits.
  • Change in Treatment Satisfaction Over Time Using the HIV Treatment Satisfaction Change Questionnaire (HIVTSQc) [ Time Frame: At Month 12 ]
    HIVTSQc (change version) total treatment satisfaction score is computed with 1-11 items. Items 1-11 are summed to produce score with possible range:-33 to 33. Higher scores represent greater improvement in treatment satisfaction compared to satisfaction with treatment received during the induction phase; lower scores represented deterioration in satisfaction with treatment. A score of 0 represents no change. A maximum of 5 items can be missing, the missing scores were 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 remain missing.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
  • Number of subjects with plasma HIV-1 RNA <50 c/mL (c/mL) at Month 12 using the FDA Snapshot algorithm [ Time Frame: At Month 12 ]
    Plasma samples will be collected from the subject at specific timepoints. The Abbott RealTime HIV-1 Assay with LLOD 40 c/mL, will be used.
  • Number of subjects with protocol defined confirmed virologic failure (CVF) over time [ Time Frame: Up to 40 months ]
    CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL.
  • Number of subjects with HIV-RNA greater than or equal to 50 c/mL as per FDA Snapshot algorithm over time [ Time Frame: Up to 40 months ]
    Plasma samples will be collected from the subject at specific time points. The Abbott RealTime HIV-1 Assay with LLOD 40 c/mL, will be used.
  • Absolute values of HIV- viral load over time [ Time Frame: Up to 40 months ]
    Plasma samples will be collected at specific time points. This will measure the number of viral particles present in the plasma.
  • Absolute values of cluster of differentiation 4 (CD4+) cell counts over time [ Time Frame: Up to 40 months ]
    Plasma samples will be collected at specific time points. The CD4+ cells is a glycoprotein found on the surface of immune cells such as the T-helper cells, monocytes, macrophages.
  • Change from Baseline in HIV viral load over time [ Time Frame: Baseline and Up to 40 months ]
    Plasma samples will be collected at specific time points. This will measure the number of viral particles present in the plasma. Change from Baseline was defined as the post-Baseline value minus the value at Baseline.
  • Change from Baseline in CD4+ cell count over time [ Time Frame: Baseline and Up to 40 months ]
    Plasma samples will be collected at specific time points. The CD4+ cells is a glycoprotein found on the surface of immune cells such as the T-helper cells, monocytes, macrophages. Change from Baseline was defined as the post-Baseline value minus the value at Baseline.
  • Number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 40 months ]
    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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment, and is associated with liver injury and impaired liver function
  • Number of subjects who discontinue treatment due to AEs over time. [ Time Frame: Up to 40 months ]
    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. Number of subjects who will discontinue the treatment due to AEs will be reported.
  • Number of subjects with abnormal hematology findings [ Time Frame: Up to 40 months ]
    Blood samples will be collected to measure platelets, white blood cell (WBC count), red blood cell (RBC) count, reticulocyte count, hemoglobin, hematocrit, RBC indices, mean corpuscular volume (MCV), basophils, eosinophils, lymphocytes, monocytes and neutrophils.
  • Number of subjects with abnormal clinical chemistry findings [ Time Frame: Up to 40 months ]
    Blood samples will be collected to measure blood urea nitrogen (BUN), creatinine, fasting glucose, sodium, potassium, chloride, Total carbon dioxide (CO2), lipase, phosphorous, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine phosphokinase (CK), creatinine clearance, albumin.
  • Number of subjects with abnormal lipid findings [ Time Frame: Up to 40 months ]
    Subjects will be advised to do overnight fasting and then samples will be assessed for abnormal Total cholesterol, High density lipoprotein (HDL) cholesterol , Low density lipoprotein (LDL) cholesterol, and triglycerides.
  • Change from Baseline in hematology parameters of platelets, WBC count, basophils, eosinophils, lymphocytes, monocytes and neutrophils [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure platelets, WBC count, basophils, eosinophils, lymphocytes, monocytes and neutrophils.
  • Change from Baseline in hematology parameters of RBC count [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure RBC count .
  • Change from Baseline in hematology parameters- Hemoglobin [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure Hemoglobin.
  • Change from Baseline in hematology parameter of hematocrit [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure hematocrit.
  • Change from Baseline in clinical laboratory parameters of sodium, potassium, carbon-dioxide (total), chloride, and glucose [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure sodium, potassium, carbon-dioxide (total), chloride, and glucose.
  • Change from Baseline in clinical laboratory parameters of creatinine and total bilirubin [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure creatinine and total bilirubin .
  • Change from Baseline in clinical laboratory parameters of ALT, ALP and AST [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure ALT, ALP and AST
  • Change from Baseline in clinical laboratory parameters of Creatine phosphokinase [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure Creatine phosphokinase.
  • Change from Baseline in clinical laboratory parameters of Creatinine clearance [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure Creatinine clearance
  • Change from Baseline in clinical laboratory parameters of lipase [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure lipase.
  • Change from Baseline in urinalysis parameters, urine albumin to creatinine ratio [ Time Frame: Baseline and Up to 40 months ]
    Urine samples will be collected at the specified timepoints, for assessment of urine albumin to creatinine ratio.
  • Change from Baseline in urinalysis parameters, urine protein to creatinine ratio [ Time Frame: Baseline and Up to 40 months ]
    Urine samples will be collected at the specified timepoints, for assessment of urine protein to creatinine ratio
  • Change from Baseline in urinalysis parameters, urine phosphate [ Time Frame: Baseline and Up to 40 months ]
    Urine samples will be collected at the specified timepoints, for assessment of urine phosphate
  • Change from Baseline in fasting lipid parameters: Total cholesterol, HDL cholesterol, LDL cholesterol, and Triglycerides [ Time Frame: Baseline and Up to 40 months ]
    Blood samples will be collected to measure, the change from Baseline values for Total cholesterol, HDL cholesterol, LDL cholesterol, and Triglycerides
  • Number of subjects with treatment emergent genotypic resistance for CAB, RPV, and DTG plus RPV [ Time Frame: Up to 40 months ]
    Whole venous blood samples will be obtained from each subject to provide peripheral blood mononuclear cells (PBMCs) and plasma for storage samples. Analysis will be done to conduct for protease (PRO), reverse transcriptase (RT), and integrase assays.
  • Trough concentrations (Ctrough) for CAB LA [ Time Frame: Pre-dose: Day 1 and Month 12 ]
    Serial blood samples will be collected at specific timepoints for PK analysis.
  • Number of subjects with treatment emergent phenotypic resistance for CAB, RPV, and DTG plus RPV [ Time Frame: Up to 40 months ]
    Whole venous blood samples will be obtained from each subject to provide PBMCs and plasma for storage samples. Analysis will be done to conduct for PRO, RT, and integrase assays.
  • Ctrough for RPV LA [ Time Frame: Pre-dose: Day 1 and Month 12 ]
    Serial blood samples will be collected at specific timepoints for PK analysis.
  • Change from Baseline (Day 1) in HIV Dependent Quality of Life (HIVDQoL) [ Time Frame: Baseline and Up to Month12 ]
    The HIVDQoL is an individualized, self-completion questionnaire, specifically designed to measure quality of life in people living with HIV. The HIVDQoL was based on Audit of Diabetes-Dependent Quality of Life (ADDQoL) -a widely used questionnaire designed for diabetics and linguistically validated in more than 60 languages. The HIVDQoL includes two overview items, 26 condition-specific domain items and a free text box. The overview items ask subjects to rate their generic 'present QoL' (7-point Likert scale, ranging from 3 [excellent] to -3 [extremely bad]) and HIV-specific 'impact of HIV on QoL' (5-point Likert scale, ranging from 3 [very much better] to 1 [worse]). The "Preference" question will contain a single item exploring whether subjects prefer the CAB LA + RPV LA injectable to the oral CAB + RPV regimen administered in LATTE. The "Reason for Switch" question will contain a single item exploring the reasons why subjects are interested in switching to the CAB LA + RPV LA.
  • Change from baseline (Day 1) in HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) [ Time Frame: Baseline and Up to Month12 ]
    The HIVTSQ is a 10-item self-reported scale which will measure the overall satisfaction with treatment and by specific domains e.g. convenience, flexibility. The items will be summed up to produce a treatment satisfaction score (0 to 60) and an individual satisfaction rating for each item (0 to 6) and two subscales: general satisfaction/clinical and lifestyle/ease subscales. The higher the score, the greater the improvement in treatment satisfaction as compared to the past few weeks. A smaller score represents a decline in treatment satisfaction compared to the past few weeks. Change from Baseline was defined as the post-Baseline value minus the value at Baseline.
  • Change in treatment satisfaction over time using the HIV Treatment Satisfaction Change Questionnaire (HIVTSQc) [ Time Frame: Baseline and Up to Month12 ]
    HIVTSQc is 12-item questionnaire, which retains option of calculating the total score as if it only had the original 10 items (as the original 10 items are included in the HIVTSQ 12). In addition, it allows for calculation of an 11-item scale score including the "easy/difficult" item (item-11). The "pain/discomfort" item (item-12) will be included in questionnaire as a stand-alone item to evaluate potentially painful injectables. Overall satisfaction with treatment and by specific domains e.g. convenience, flexibility is assessed. The items are summed up to produce treatment satisfaction score (0 to 60) and an individual satisfaction rating for each item (0 to 6) and two subscales: general satisfaction/clinical and lifestyle/ease subscales. Higher the score, greater the improvement in treatment satisfaction as compared to the past few weeks. Change from Baseline was defined as the post-Baseline value minus the value at Baseline.
Current Other Pre-specified Outcome Measures
 (submitted: November 20, 2020)
  • Plasma Trough Concentration (Ctrough) for CAB LA [ Time Frame: Pre-dose (Day 1) and Month 12 ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of CAB LA. This was a conditional secondary endpoint for which results are not available because the trough concentrations for this product are well characterized and therefore, secondary population pharmacokinetic (Pop PK) analyses were not conducted.
  • Ctrough for RPV LA [ Time Frame: Pre-dose (Day 1) and Month 12 ]
    Blood samples were collected at indicated time points for pharmacokinetic analysis of RPV LA. This was a conditional secondary endpoint for which results are not available because the trough concentrations for this product are well characterized and therefore, secondary Pop PK analyses were not conducted.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2b, Open-label, Multicenter, Rollover Study to Assess Antiviral Activity and Safety of Long-acting (LA) Cabotegravir (CAB) Plus LA Rilpivirine (RPV), Administered Every 2 Months (Q2M), in Human Immunodeficiency Virus (HIV)-Positive Participants From the LATTE Study
Official Title  ICMJE A Phase IIb, Multicenter, Open-label, Rollover Study Evaluating the Efficacy, Safety and Tolerability of Long-acting Cabotegravir Plus Long-acting Rilpivirine Administered Every Two Months in HIV-1 Infected Adults Who Are Virologically Suppressed and Participated in Study LAI116482
Brief Summary This study (POLAR), is designed to assess the antiviral activity and safety of CAB LA plus RPV LA, administered Q2M, in approximately 100 adult HIV-1 infected, antiretroviral therapy (ART) experienced participants. Participants will rollover from the NCT01641809 (LATTE) study, who have completed minimum duration of Week 312 and with demonstrated HIV-1 ribonucleic acid (RNA) suppression (less than [<]50 copies (c) per milliliter [mL]), while receiving a two-drug regimen consisting of once-daily oral CAB at 30 milligram (mg) plus RPV at 25 mg. The participants will be offered the option to switch to the LA, intramuscular injections of CAB LA plus RPV LA, Q2M or the oral fixed dose combination (FDC) of dolutegravir (DTG) plus RPV, for the continued maintenance of HIV-1 RNA suppression, known as the Maintenance Phase (From Day 1 to Commercial Approval). Duration of study will vary from country to country, until regimen receives regulatory approval and becomes commercially available. The study plans to enroll approximately 100 participants. Any participant who receives at least one dose of CAB LA and/or RPV LA and discontinues the CAB LA plus RPV LA regimen for any reason will enter a 52-week Long-Term Follow-Up (LTFU) phase. Those participants must remain on suppressive highly active antiretroviral therapy (HAART) for at least 52 weeks after the last dose of CAB LA and or RPV LA.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is an Intervention Model, with parallel assignment, where the primary purpose of the study is, treatment, with 2 arms and no masking.
Masking: None (Open Label)
Masking Description:
This is an open-label study, thus no masking.
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: CAB LA
    Administered CAB LA (600 mg) Q2M, as intramuscular injection.
  • Drug: RPV LA
    Administered RPV LA (900 mg), Q2M, as intramuscular injection.
  • Drug: RPV
    Oral dose of RPV 25 mg, administered once daily from Day 1 up to Month 12
  • Drug: DTG
    Oral dose of DTG 50 mg administered once daily from Day 1 up to Month 12.
Study Arms  ICMJE
  • Experimental: Participants receiving Injection CAB LA plus RPV LA
    The eligible participants in the arm (participants from LATTE, who were administered oral CAB 30 mg plus RPV 25 mg, who successfully complete Week 300) will receive their first dose CAB LA (600 mg) plus RPV LA (900 mg) injections within 2 hours of the final oral dose of LATTE given on the same day. The second loading injections will be administered 1 month after initial loading dose (CAB LA 600 mg plus RPV LA 900 mg), with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring Q2M thereafter. Participants will continue to receive the treatment until the study intervention is locally approved and commercially available. HAART therapy will be initiated within 8 weeks after the last Q2M injection.
    Interventions:
    • Drug: CAB LA
    • Drug: RPV LA
  • Experimental: Participants receiving Oral DTG plus RPV
    The eligible participants in the arm (participants from LATTE, who were administered oral CAB 30 mg plus RPV 25 mg, who successfully complete Week 300) will receive their first dose of the DTG 50 mg plus RPV 25 mg, once daily as oral regimen on Day 1 until Month 12. Participants will continue to receive the treatment until the study intervention is locally approved and commercially available.
    Interventions:
    • Drug: RPV
    • Drug: DTG
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: November 20, 2020)
97
Original Estimated Enrollment  ICMJE
 (submitted: August 20, 2018)
100
Estimated Study Completion Date  ICMJE April 29, 2022
Actual Primary Completion Date December 11, 2019   (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.
  • A female participant is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG] test at Day 1), not lactating, and at least with one of following conditions:

    (a) Non-reproductive potential defined as: (i) Pre-menopausal females with one of the conditions as documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy.

(ii) 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 (refer to laboratory reference ranges for confirmatory levels)]. 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.

(b) Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication, throughout the study, for at least 30 days after discontinuation of all oral study medications, and for at least 52 weeks after discontinuation of CAB LA and RPV LA.

  • The investigator is responsible for ensuring that participants understand how to properly use the methods of contraception.
  • Capable of giving signed informed consent.
  • Must have been on oral CAB 30 mg plus RPV 25 mg regimen through at minimum Week 300 of the LATTE study as per LATTE protocol dosing requirements and until Day 1 of the POLAR study. Any disruptions in dosing during LATTE must be discussed with the Medical Monitor for a final determination of eligibility.
  • Plasma HIV-1 RNA <50 c/mL at Week 300. If participant has plasma HIV-1 RNA >= 50 c/mL at Week 300 in LATTE, a single repeat to determine eligibility may be allowed ONLY after consultation with the medical monitor.

Exclusion Criteria:

  • During the last 6 months of participation in LATTE, consecutive (2 or more sequential) plasma HIV-1 RNA measurements >=50 c/mL.
  • During the last 6 months of participation in LATTE, any HIV-1 RNA measurement >=200 c/mL.
  • Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy.
  • Participants with moderate to severe hepatic impairment determined by Child-Pugh classification.
  • Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
  • Participants determined by the Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrolment if the Investigator believes the risk of seizure recurrence is low.
  • Participants who, in the investigator's judgment, pose a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
  • Participants 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 for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV DNA as follows; Participants positive for HBsAg are excluded; participants 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; participants who are anticipated to require HCV treatment within 12 months must be excluded. (HCV treatment on study may be permitted, following consultation with the medical monitor).
  • Participants with HCV co-infection will be allowed entry into this study if: Liver enzymes meet entry criteria; HCV Disease has undergone appropriate work-up, and is not advanced.
  • Additional information (where available) on participants, with HCV co-infection at screening should include results from any liver biopsy, Fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment.
  • In the event that recent biopsy or imaging data is not available or inconclusive, the fibrosis- 4 (Fib-4) score will be used to verify eligibility where Fib-4 score >3.25 is exclusionary; Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation where the Fibrosis 4 Score Formula: age multiplied by aspartate amino transferase (AST) divided by platelets multiplied by square of alanine aminotransferase (ALT).
  • Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
  • History of liver cirrhosis with or without hepatitis viral co-infection.
  • Ongoing or clinically relevant pancreatitis.
  • Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease.
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the participant prior to randomization.
  • Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication.
  • History or presence of allergy or intolerance to the study drugs or their components or drugs of their class. In addition, if heparin is used during pharmacokinetic (PK) sampling, participants with a history of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled.
  • Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (less than or equal to [<=]325 mg) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
  • Corrected QT interval (QTc (Bazett)) >450 millisecond (msec) or QTc (Bazett) >480 msec for participants with bundle branch block.
  • Any verified Grade 4 laboratory abnormality over the last 6 months in LATTE. A single repeat test is allowed to verify a result.
  • Any acute laboratory abnormality over the last 6 months in LATTE, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.
  • ALT>=5 times upper limit of normal (ULN) or ALT >= 3 times ULN and bilirubin >= 1.5 times ULN (with >35 percent [%] direct bilirubin) over the last 6 months in LATTE.
  • Exposure to an experimental drug (with the exception of those in the LATTE study including CAB and RPV) 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 Day 1: 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.
  • Use of medications which are associated with Torsade de Pointes must be discussed with the Medical Monitor to determine eligibility.
  • Participants 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 Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03639311
Other Study ID Numbers  ICMJE 209035
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  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, key secondary endpoints and safety data 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, LP
Investigators  ICMJE
Study Director: GSK Clinical Trials ViiV Healthcare
PRS Account ViiV Healthcare
Verification Date February 2021

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