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Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants

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ClinicalTrials.gov Identifier: NCT02938520
Recruitment Status : Active, not recruiting
First Posted : October 19, 2016
Last Update Posted : October 15, 2018
Sponsor:
Collaborators:
Janssen Pharmaceuticals
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

September 15, 2016
October 19, 2016
October 15, 2018
October 27, 2016
August 30, 2018   (Final data collection date for primary outcome measure)
Proportion of participants with plasma HIV 1 Ribonucleic acid <50 copies/milliliter (c/mL) at Week 48 [ Time Frame: Week 48 ]
Virologic failure (HIV-1 RNA >= 50 c/mL) based on the 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).
Proportion of participants with plasma HIV 1 Ribonucleic acid <50 copies/milliliter (c/mL) at Week 48 [ Time Frame: Week (Wk) 48 ]
Virologic failure (HIV-1 RNA ≥ 50 c/mL) based on theFood 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)
Complete list of historical versions of study NCT02938520 on ClinicalTrials.gov Archive Site
  • Proportion of participants with Plasma HIV-1 RNA <50 c/mL at Week 48 [ Time Frame: Week 48 ]
    It will be assessed using the FDA Snapshot algorithm at Week 48 and is a key secondary endpoint.
  • Proportion of participants with plasma HIV-1 RNA <200 c/mL [ Time Frame: Week 48 and Week 96 ]
    It will be assessed using the FDA Snapshot algorithm at Week 48 and Week 96
  • Proportion of participants with plasma HIV-1 RNA >=50 c/mL at Week 96 [ Time Frame: Week 96 ]
    Proportion of participants with a virologic failure based on the 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) will be assessed.
  • Proportion of participants with confirmed virologic failure at Week 48 and Week 96 [ Time Frame: Week 48 and Week 96 ]
    For the purposes of clinical management in this study, virologic failure is defined as any of the following: Non-response as indicated by a less than a 1.0 log10 c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Phase, which is subsequently confirmed, unless the plasma HIV-1 RNA is < 400 c/mL (Induction Phase criteria), Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is >=200 c/mL (Induction Phase criteria), Rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to < 200 c/mL
  • Change from Baseline in plasma HIV-1 RNA at Week 48 and Week 96 [ Time Frame: Baseline (Day 1), Weeks 48 and 96 ]
    It will be analyzed overtime, including Week 48 and Week 96
  • Change from Baseline in CD4+ cell counts [ Time Frame: Baseline (Day 1) and up to Week 96 ]
    It will be analyzed overtime, including Week 48 and Week 96
  • Number of participants with disease progression [ Time Frame: Baseline (Day 1) and up to Week 96 ]
    It will be assessed overtime, including Week 48 and Week 96 (HIV-associated conditions, acquired immunodeficiency syndrome [AIDS] and death)
  • Number of participants with adverse events (AEs), serious AEs (SAEs) and AEs by severity [ Time Frame: Up to Week 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). Severity will be analyzed as mild, moderate and severe AEs.
  • Number of participants with laboratory abnormalities [ Time Frame: Up to Week 96 ]
    It will be analyzed overtime, including Week 48 and Week 96
  • Number of participants who discontinue treatment due to AEs [ Time Frame: Up to Week 96 ]
    Participants who discontinue treatment due to AEs will be analyzed overtime, including Week 48 and Week 96
  • Number of participants with abnormal change from Baseline in laboratory parameters. [ Time Frame: Baseline (Day 1) and up to Week 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 time, including Week 48 and Week 96
  • Change from Baseline in fasting lipids [ Time Frame: Baseline (Day 1) and up to Week 96 ]
    Fasting lipid panel includes; Total cholesterol, high density lipid (HDL) cholesterol, low density lipid (LDL) cholesterol and triglycerides will be analyzed over time, including Week 48 and Week 96
  • Number of participants with treatment emergent resistance [ Time Frame: Up to Week 96 ]
    Genotypic and phenotypic resistance to treatments; CAB, RPV, and other on-study antiretroviral treatment (ART) over time, including Week 48 and Week 96
  • Plasma trough concentration (Ctrough) for CAB LA arm [ Time Frame: Pre-dose at Weeks 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100, 101, 104a, 104b, 108. ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Weeks 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at 101 and 104a (direct to inject arm), week 104b (oral lead-in arm) for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC.
  • Plasma trough concentration (Ctrough) for RPV LA arm [ Time Frame: Pre-dose at Weeks 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100, 101, 104a, 104b, 108. ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Weeks 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at 101 and 104a (direct to inject arm), week 104b (oral lead-in arm) for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC.
  • Maximum concentration (Cmax) in plasma for CAB LA arm [ Time Frame: At anytime post-dose at Weeks 5, 41 and 101 ]
    Blood sample will be obtained to evaluate Cmax of CAB.
  • Maximum concentration (Cmax) in plasma for RPV LA arm [ Time Frame: At anytime post-dose at Weeks 5, 41 and 101 ]
    Blood sample will be obtained to evaluate Cmax of RPV.
  • Plasma area under the concentration-time curve (AUC) for CAB LA arm [ Time Frame: Pre-dose at Weeks 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100, 101, 104a, 104b, 108; At anytime post-dose at Weeks 5, 41 and 101 ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Weeks 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at 101 and 104a (direct to inject arm), week 104b (oral lead-in arm) for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Post-dose sample will be collected at Weeks 5, 41 and 101 in IM arm.
  • Plasma area under the concentration-time curve (AUC) for RPV LA arm [ Time Frame: Pre-dose at Weeks 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100, 101, 104a, 104b, 108; At anytime post-dose at Weeks 5, 41 and 101 ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Weeks 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at 101 and 104a (direct to inject arm), week 104b (oral lead-in arm) for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Post-dose sample will be collected at Weeks 5, 41 and 101 in IM arm.
  • Change from Week 5 in Dimension Scores [ Time Frame: Week 5 and up 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 Withdrawal.
  • Change from baseline in health related quality of life (HR QoL) [ Time Frame: Baseline (Day 1) and up to Week 96 ]
    HR QoL will be assessed using the HIV/AIDS targeted quality of life questionnaire (HAT-QoL) short form at Baseline (Day 1), Week 24, Week 48, Week 96 (or Withdrawal).
  • Change from baseline in treatment satisfaction [ Time Frame: Day 1 up to Week 96 ]
    The HIV Treatment Satisfaction Questionnaire-status-12 (HIVTSQs-12) will be used to assess the "Total Treatment Satisfaction" score and individual item scores of the HIV Treatment Satisfaction Questionnaire (status version) (HIVTSQs) at Week 4b, Week 24, Week 44, Week 96 (or Withdrawal). The change from baseline (Day 1) in HIVTSQs total score at Week 44 is a key secondary endpoint.
  • Change in treatment satisfaction at Week 48 [ Time Frame: Baseline (Day 1) and up to Week 48 ]
    Change in treatment satisfaction over time (using the HIVTSQ change version [HIVTSQc]) at Week 48 (or Withdrawal) will be assessed.
  • Change from Baseline in health status [ Time Frame: Baseline (Day 1) and up to Week 96 ]
    Overall health status will be assessed using the 12-item Short Form Survey (SF-12) at Day 1 and weeks 24, 48, 96 and/or WD
  • Change from Baseline in treatment acceptance [ Time Frame: Baseline (Day 1) and up to Week 96 ]
    Overall treatment acceptance to chronic therapy will be assessed using the "General Acceptance" dimension of the Chronic Treatment Acceptance (ACCEPT) questionnaire. It will be assessed at Day 1 and weeks 8, 24, 48, 96 and/or WD
  • Change in tolerability of injection (for CAB LA + RPV LA) [ Time Frame: Week 4b and up to Week 96 ]
    Patient reported injection tolerability will be assessed using the Numeric Rating Scale (NRS) within the CAB LA + RPV LA arm. NRS will be assessed at weeks 4b, 5, 40, 41, and 96
  • Number of participants with potential predictors of inter- and intra-subject variability for pharmacokinetic parameters [ Time Frame: Up to Week 96 ]
    Demographic parameters and laboratory parameters will be evaluated as potential predictors of inter- and intra-participant variability for pharmacokinetic parameters. Number of subjects with identified potential predictors will be assessed.
  • Proportion of participants considering pain and local reactions following injection to be extremely or very acceptable [ Time Frame: Week 5 to Week 96 ]
    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 will be assessed.
  • Proportion of participants with HIV-1 RNA >= 50 c/mL at Week 124 in extension phase [ Time Frame: Up to Week 124 ]
    Proportion of participants with HIV-1 RNA >= 50 c/mL at Week 124, with and without oral lead-in (FDA Snapshot algorithm, Extension Switch population) will be assessed.
  • Proportion of participants with plasma HIV-1 RNA <50 c/mL over time in extension phase [ Time Frame: Up to Week 124 ]
    Proportion of participants with plasma HIV-1 RNA <50 c/mL over time will be assessed.
  • Proportion of participants with plasma HIV-1 RNA <200 c/mL over time in extension phase [ Time Frame: Up to Week 124 ]
    Proportion of participants with plasma HIV-1 RNA <50 c/mL over time will be assessed.
  • Proportion of participants with confirmed virologic failure over time in extension phase [ Time Frame: Up to Week 124 ]
    Proportion of participants with confirmed virologic failure based on FDA snapshot at Week 124 will be assessed.
  • Number of participants with treatment emergent genotypic and phenotypic resistance to CAB and RPV over time in extension phase [ Time Frame: Up to Week 124 ]
    Genotypic and phenotypic resistance to treatments CAB and RPV will be assessed at Week 124.
  • Change from Baseline in CD4+ cell counts in extension phase [ Time Frame: Up to Week 124 ]
    Change from Baseline in CD4+ cell counts will be assessed at Week 124.
  • Number of participants with AEs, SAEs and AEs by severity in extension phase [ Time Frame: Up to Week 124 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. Severity will be analyzed as mild, moderate and severe AEs.
  • Number of participants with laboratory abnormalities in extension phase [ Time Frame: Up to Week 124 ]
    Number of participants with any laboratory abnormalities in extension phase will be assessed.
  • Number of participants with abnormal change from baseline in laboratory parameters in extension phase [ Time Frame: Up to Week 124 ]
    Laboratory parameters includes; 1. Hematology parameters-platelet count, RBC count, 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.
  • Number of participants who discontinue treatment due to AEs in extension phase [ Time Frame: Up to Week 124 ]
    Participants who discontinue treatment due to AEs will be analyzed up to Week 124.
  • Plasma CAB and RPV concentrations in the Extension Phase (direct to inject without oral lead-in) [ Time Frame: Weeks 100, 101 and 104a ]
    It will be assessed for for participants switching from ABC/DTG/3TC in the Extension Phase (direct to inject without oral lead-in).
  • Plasma CAB and RPV concentrations in the Extension Phase (both direct to inject and optional oral lead-in participants) [ Time Frame: Week 104b ]
    It will be assessed for participants switching from ABC/DTG/3TC in the Extension Phase (both direct to inject and optional oral lead-in participants).
  • Proportion of participants with Plasma HIV-1 RNA <50 copies/mL (c/mL) at Week 48 [ Time Frame: Week 48 ]
    Assessed using the FDA Snapshot algorithm at Week 48 and 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 plasma HIV-1 RNA ≥ 50 c/mL at Week 96 [ Time Frame: Week 96 ]
    Proportion of participants with a virologic failure based on the 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)
  • Proportion of participants with confirmed virologic failure [ Time Frame: Up to Week 96 ]
    For the purposes of clinical management in this study, virologic failure is defined as any of the following:Non-response as indicated by a less than a 1.0 log10 c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Phase, which is subsequently confirmed, unless the plasma HIV-1 RNA is < 400 c/mL (Induction Phase criteria), Rebound as indicated by two consecutive plasma HIV-1 RNA that are > 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is ≥200 c/mL (Induction Phase criteria), Rebound as indicated by two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to < 200 c/mL. Analysed over time, including Week 48 and Week 96
  • Change from Baseline in plasma HIV-1 RNA [ Time Frame: Baseline and up to Week 96 ]
    Will be analyzed overtime, including Week 48 and Week 96
  • Change from Baseline in CD4+ cell counts [ Time Frame: Baseline and up to Week 96 ]
    Will be analyzed overtime, including Week 48 and Week 96
  • Incidence of disease progression. [ Time Frame: Baseline and up to Week 96 ]
    Will be assessed overtime, including Week 48 and Week 96 (HIV-associated conditions, acquired immunodeficiency syndrome AIDS and death)
  • Incidence and severity of adverse events (AEs) [ Time Frame: Up to Week 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 overtime, including Week 48 and Week 96.
  • Incidence and severity of laboratory abnormalities [ Time Frame: Up to Week 96 ]
    Incidence and severity will be analyzed overtime, including Week 48 and Week 96
  • Proportion of participants who discontinue treatment due to AEs. [ Time Frame: Up to Week 96 ]
    Participants who discontinue treatment due to AEs will be analyzed overtime, including Week 48 and Week 96
  • Number of participants having changes in laboratory parameters. [ Time Frame: Baseline and up to Week 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 time, including Week 48 and Week 96
  • Change from Baseline in fasting lipids. [ Time Frame: Baseline and up to Week 96 ]
    Fasting lipid panel includes; Total cholesterol, high density lipid (HDL) cholesterol, low density lipid (LDL) cholesterol and triglycerides will be analyzed over time, including Week 48 and Week 96
  • Incidence of treatment emergent resistance [ Time Frame: Baseline and up to Week 96 ]
    Genotypic and phenotypic resistance to treatments; CAB, RPV, and other on-study antiretroviral treatment (ART) over time, including Week 48 and Week 96
  • Plasma trough concentration (Ctrough) for CAB LA arm [ Time Frame: Blood samples will be collected at Weeks 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100, 104b, 108, and Withdrawal. ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Wk 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at Wk 104b and 108 for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Samples will also be obtained at the Withdrawal (WD) visit.
  • Plasma trough concentration (Ctrough) for RPV LA arm [ Time Frame: Blood samples will be collected at Weeks 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100, 104b, 108, and Withdrawal ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Wk 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at Wk 104b and 108 for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Samples will also be obtained at the WD visit.
  • Maximum concentration (Cmax) in plasma for CAB LA arm [ Time Frame: Wk 5 and 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 41 ]
    Blood sample will be obtained from participants at Post-dose
  • Plasma area under the concentration-time curve (AUC) for CAB LA arm [ Time Frame: Blood samples will be collected at Wk 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100, 104b, and 108. ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Wk 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at Wk 104b and 108 for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Post-dose sample will be collected at Wk 5, Wk 41 in IM arm.
  • Plasma area under the concentration-time curve (AUC) for RPV LA arm [ Time Frame: Blood samples will be collected at Wk 4b, 5, 8, 12, 16, 20, 24, 28, 32, 36, 40, 41, 44, 48, 52, 56, 60, 96, 100, 104b, and 108. ]
    Blood sample will be obtained from participants at the given time points. Pre dose sample will be collected at Wk 4b, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 96, 100 and 108 in IM arm and at Wk 104b and 108 for participants transitioning to CAB LA + RPV LA from ABC/DTG/3TC. Post-dose sample will be collected at Wk 5, Wk 41in IM arm.
  • Acceptance of injection-related pain and injection site reactions (ISRs) (for CAB LA + RPV LA) [ Time Frame: Week 5 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 (HR QoL) [ Time Frame: Day 1 up to Week 96 ]
    HR QoL will be assessed using the HIV/AIDS-targeted quality of life (HAT-QOL) questionnaire short form on Day 1 and Week 24, Week 48, Week 96, (or WD)
  • Change from baseline in treatment satisfaction [ Time Frame: Day 1 up to Week 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 Day 1 and weeks 4b, 24, 44, 96 and/or WD. The change from baseline (Day 1) in HIVTSQs total score at Week 44 is a key secondary endpoint.
  • Change from previous therapy in treatment satisfaction [ Time Frame: Week 48 and/or WD ]
    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 48 and/or WD
  • Change in health status [ Time Frame: Day 1 up to Week 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 Day 1 and weeks 24, 48, 96 and/or WD
  • Change in treatment acceptance. [ Time Frame: Day 1 up to Week 96 ]
    Overall treatment acceptance to chronic therapy will be assessed with 3 items from the ACCEPT questionnaire. It will be assessed at Day 1 and weeks 8, 24, 48, 96 and/or WD
  • Change in tolerability of injection (for CAB LA + RPV LA) [ Time Frame: Week 4b and up to Week 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: 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.
Not Provided
Not Provided
 
Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants
A Phase III, Randomized, Multicenter, Parallel-group, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Long-Acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor Single Tablet Regimen in HIV-1 Infected Antiretroviral Therapy Naive Adult Participants
The First Long-Acting Injectable Regimen (FLAIR) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult participants whose virus is virologically suppressed on an integrase inhibitor single tablet regimen (INI STR) will remain suppressed after switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In this study, the INI STR will be limited to abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). FLAIR is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, anti-retroviral therapy (ART)-naïve adult participants. 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 to remaining on ABC/DTG/3TC over 48 weeks (4 weeks oral CAB + RPV, 44 weeks LA therapy). Participants who are HLA-B*5701 positive at Screening may enroll into the study and receive DTG plus a non-abacavir containing dual nucleoside reverse transcriptase inhibitor (NRTI) regimen. Eligible participants will enroll into the Induction Phase of the study and receive ABC/DTG/3TC for 20 weeks (Week [-20] to Day 1). Participants who have an HIV 1 ribose nucleic acid (RNA) <50 copies per milliliter (c/mL) at Week (-4) will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue ABC/DTG/3TC or to discontinue ABC/DTG/3TC and begin oral therapy with CAB 30 mg + RPV 25 mg once daily for approximately 4 Weeks, followed by monthly CAB LA + RPV LA injections from visit Week 4b until study completion or withdrawal. Participants who successfully complete Week 100 (without meeting study defined withdrawal criteria and who remain virologically suppressed through Week 96: HIV-1 RNA <50 c/mL) will be given the option to switch to the LA arm in the Extension Phase (using an optional oral lead-in with CAB + RPV) or be withdrawn from the study. Participants will continue to receive injections every 4 weeks during the Extension Phase until CAB LA and RPV LA are either locally approved and commercially available, the participant no longer derives clinical benefit, the participant meets a protocol-defined reason for discontinuation, or until development of either CAB LA or RPV LA is terminated.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
HIV Infections
  • 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: ABC/DTG/3TC STR - Tablet
    It is a purple, biconvex, oval, tablet debossed with "572 Tri" on one side, film-coated tablet contains abacavir sulphate equivalent to 600 mg of abacavir, dolutegravir sodium equivalent to 50 mg dolutegravir, and 300 mg of lamivudine. The inactive ABC/DTG/3TC tablet ingredients include D-mannitol, magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate.
  • Drug: DTG Tablet
    It is a yellow, round, biconvex, 50 mg film-coated tablet debossed with "SV 572" on one side and "50" on the other side. Each tablet of DTG also contains the following inactive ingredients: D-mannitol, microcrystalline cellulose, povidone K29/32, sodium starch glycolate, and sodium stearyl fumarate.
  • Experimental: CAB LA + RPV LA every 4 weeks
    After Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will receive oral CAB 30 mg + RPV 25 mg once daily for approximately four weeks. At visit Week 4b subjects will receive an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4b. From Week 8 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: ABC / DTG / 3TC (600 mg/50mg/300mg) once daily
    After the Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will continue to receive oral ABC/DTG/3TC (or DTG + two NRTIs) initiated during the Induction Phase for 100 weeks. At the end of the Maintenance Phase, eligible participants receiving ABC/DTG/3TC (or DTG + two NRTIs) have the option to continue in the study by switching to CAB LA + RPV LA in the Extension Phase. These participants will transition to LA dosing, beginning with approximately 4 weeks of oral CAB + RPV therapy initiated at Week 100, and receive the first IM CAB LA + RPV LA injections at Week 104b.
    Interventions:
    • Drug: ABC/DTG/3TC STR - Tablet
    • Drug: DTG Tablet
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
631
620
July 7, 2022
August 30, 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria: - HIV-1 infected, ART-naive men or women aged 18 years or greater at the time of signing the informed consent. - HIV-1 infection as documented by Screening plasma HIV-1 RNA >=1000 c/mL; - Antiretroviral-naive (<=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection). Any previous exposure to an HIV integrase inhibitor or non-nucleoside reverse transcriptase inhibitor will be exclusionary. - Female Participants: A female participant is eligible to participate if she is not pregnant at Screening and first day of Induction Phase (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies: 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. 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, 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 participants understand how to properly use these methods of contraception. All participants in the study should be counseled 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. - Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. - In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria: - Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed during the study. - Any evidence at Screening of an active Centers for Disease and Prevention Control (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy or historic or current cluster of differentiation4+ (CD4+) cell count <200 cells/ cubic millimeter (mm^3) are not exclusionary. - Participants with known moderate to severe hepatic impairment. - Any pre-existing physical or mental condition (including substance abuse 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. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment. - Participant who, in the investigator's judgment, poses a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk. - The participant has a tattoo 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 dioxyribose nucleic acid (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. Note: Participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not 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 prior to Week 48 of the Maintenance Phase must be excluded. HCV treatment on study may be permitted post Week 48, following consultation with the Medical Monitor. Participants 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, HCV is not advanced, and will not require treatment prior to the Week 48 visit. Additional information (where available) on participants with HCV co-infection at screening should include results from any liver biopsy, fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment. In the event that recent biopsy or imaging data is not available or is inconclusive, the Fib-4 score will be used to verify eligibility. A 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 [square root of ALT]). - Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), 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. - All participants will be screened for syphilis (rapid plasma reagin [RPR]). Participants with untreated syphilis infection, defined as a positive RPR without clear documentation of treatment, are excluded. Participants with a positive RPR test who have not been treated may be rescreened at least 30 days after completion of antibiotic treatment for syphilis. - Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the study Medical Monitor for inclusion of the participant prior to enrollment. - Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug 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 sampling (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. - Alanine aminotransferase (ALT) >=3 times upper limit normal (ULN). - 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. - Exposure to an experimental drug and/or experimental vaccine within 28 days or 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product (IP). - Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; tuberculosis (TB) therapy, with the exception of treatment of latent TB with isoniazid; Immunomodulators that alter immune responses (such as chronic systemic corticosteroids, interleukins, or interferons). Note: Participants using short-term (e.g. =<21 day) systemic corticosteroid treatment, topical, inhaled or intranasal corticosteroids are eligible for enrollment. - 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 the first dose of IP. - Use of medications which are associated with Torsades de Pointes - Any evidence of primary resistance to non-nuclease reverse transcriptase inhibitors (NNRTIs) (except for K103N which is allowed), or any known resistance to INIs from historical resistance test results. Note: re-tests of Screening genotypes are allowed only at the discretion of the study virologist. - Participants who are HLA-B*5701 positive and are unable to use an nuclease reverse transcriptase inhibitors (NRTI) backbone that does not contain abacavir (participants who are HLA-B*5701 positive may be enrolled if they use a NRTI backbone that does not contain abacavir; HLA-B*5701 positive participants may be excluded from the study if local provision of an alternate NRTI backbone is not possible). - Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening Phase to verify a result. - Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the participant's participation in the study of an investigational compound. - Participant has estimated creatinine clearance <50 mL/min/1.73m^2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. - Participants who are currently participating in or anticipate to be selected for any other interventional study.

Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   France,   Germany,   Italy,   Japan,   Netherlands,   Russian Federation,   South Africa,   Spain,   United Kingdom,   United States
 
 
NCT02938520
201584
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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
ViiV Healthcare
ViiV Healthcare
  • Janssen Pharmaceuticals
  • GlaxoSmithKline
Study Director: GSK Clinical Trials ViiV Healthcare
ViiV Healthcare
October 2018

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