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Strategy-confirming Study of BMS-955176 to Treat HIV-1 Infected Treatment-experienced Adults

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ClinicalTrials.gov Identifier: NCT02386098
Recruitment Status : Terminated (GI Intolerability)
First Posted : March 11, 2015
Results First Posted : August 20, 2018
Last Update Posted : August 20, 2018
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Tracking Information
First Submitted Date  ICMJE March 6, 2015
First Posted Date  ICMJE March 11, 2015
Results First Submitted Date  ICMJE June 4, 2018
Results First Posted Date  ICMJE August 20, 2018
Last Update Posted Date August 20, 2018
Actual Study Start Date  ICMJE July 8, 2015
Actual Primary Completion Date June 7, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2018)
  • Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <40 Copies Per Milliliter (c/mL) at Week 24-Stage 1 [ Time Frame: Week 24 ]
    Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. Percentage of participants with plasma HIV-1 RNA <40 c/mL at Week 24 was assessed using the Food and Drug Administration (FDA) snapshot algorithm which used the last on-treatment plasma HIV-1 RNA measurement, within an FDA-specified visit window (18 to 30 weeks), to determine response. Analysis was performed on the modified intent to treat (mITT) Population which comprised of all randomized participants who received atleast one dose of BMS-955176 or TDF.
  • Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Week 24-Stage 2 [ Time Frame: Week 24 ]
    Blood samples were planned to be collected for quantitative analysis of plasma HIV-1 RNA. The analysis was not performed in Stage 2 due to early termination of the study during Stage 1.
Original Primary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
The proportion of subjects with plasma HIV 1 RNA less than 40 c/mL at Week 24 [ Time Frame: Week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2018)
  • Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Weeks 48 and 96-Stage 1 [ Time Frame: Weeks 48 and 96 ]
    Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. Response was assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a participant's response status. The percentage of responders with HIV-1 RNA <40 c/mL at Weeks 48 and 96 using mITT Population (observed) which consisted of participants in the mITT Population excluding participants who had no HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (October 10, 2016) is presented. The study was terminated early during the primary end point analysis of Stage 1; hence, data was not collected for Week 96 analysis.
  • Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Weeks 48 and 96-Stage 2 [ Time Frame: Weeks 48 and 96 ]
    Blood samples were planned to be collected for quantitative analysis of plasma HIV-1 RNA. The analysis was not performed in Stage 2 due to early termination of the study during Stage 1.
  • Percentage of Participants With HIV-1 RNA <200 c/mL at Weeks 24, 48 and 96-Stage 1 [ Time Frame: Weeks 24, 48 and 96 ]
    Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. Response was assessed using the last plasma HIV-1 RNA value in the predefined visit window to classify a participant's response status. The percentage of responders with HIV-1 RNA <200 c/mL at Weeks 24, 48 and 96 using mITT Population (observed) which consisted of participants in the mITT Population excluding participants who had no HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (October 10, 2016) is presented. The study was terminated early during the primary end point analysis of Stage 1; hence, data was not collected for Week 96 analysis.
  • Percentage of Participants With HIV-1 RNA <200 c/mL at Weeks 24, 48 and 96-Stage 2 [ Time Frame: Weeks 24, 48 and 96 ]
    Blood samples were planned to be collected for quantitative analysis of plasma HIV-1 RNA. The analysis was not performed in Stage 2 due to early termination of the Study during Stage 1.
  • Change From Baseline in Logarithm to the Base 10 (log10) HIV-1 RNA Over Time-Stage 1 [ Time Frame: Baseline and up to Week 72 ]
    Blood samples were collected for analysis of HIV-1 RNA. Baseline is the last value on or before the start of study treatment. Change from Baseline was calculated as the value at specified visit minus the Baseline value. Change from Baseline in plasma HIV-1 RNA (log10) is summarized over time for the mITT Population using observed values, which excluded participants without HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). NA indicates data was not available. The standard deviation could not be calculated as a single participant was analyzed at the specified time point.
  • Change From Baseline in log10 HIV-1 RNA Over Time-Stage 2 [ Time Frame: Baseline and up to Week 96 ]
    This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.
  • Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count Over Time-Stage 1 [ Time Frame: Baseline and up to Week 72 ]
    The CD4+ cell count was assessed using flow cytometry. Baseline is the last value on or before the start of study treatment. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates data was not available. The standard deviation could not be calculated as a single participant was analyzed at the specified time point.
  • Change From Baseline in CD4+ Cell Count Over Time-Stage 2 [ Time Frame: Baseline and up to Week 96 ]
    This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.
  • Change From Baseline in Percentage of CD4+ Cells Over Time-Stage 1 [ Time Frame: Baseline and up to Week 72 ]
    The percentage of CD4+ cells was assessed using flow cytometry. Baseline is the last value on or before the start of study treatment. Change from Baseline was calculated as the value at specified visit minus the Baseline value. NA indicates data was not available. The standard deviation could not be calculated as a single participant was analyzed at the specified time point.
  • Change From Baseline in Percentage of CD4+ Cells Over Time-Stage 2 [ Time Frame: Baseline and up to Week 96 ]
    This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.
  • Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Stage 1 [ Time Frame: Up to Week 96 ]
    An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or medical events that may jeopardize the participant or require intervention (medical or surgical) to prevent one of the outcomes mentioned before. The number of participants with SAEs and AELDs are presented.
  • Number of Participants With SAEs and AELDs-Stage 2 [ Time Frame: Up to Week 96 ]
    This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.
  • Number of Participants With Occurrence of New Acquired Immunodeficiency Syndrome (AIDS) Defining Events-Stage 1 [ Time Frame: Up to Week 96 ]
    The occurrence of new AIDS defining events that is, Centers for Disease Control (CDC) Class C events in participants is presented.
  • Number of Participants With Occurrence of New AIDS Defining Events-Stage 2 [ Time Frame: Up to Week 96 ]
    This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.
  • Maximum Observed Concentration (Cmax) for BMS-955176-Stage 1 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    The pharmacokinetic (PK) assessments were planned to be performed on PK Population, which comprised of all treated participants who had any available concentration-time data; however, it was not performed due to the early termination of the study in Stage 1.
  • Cmax for BMS-955176-Stage 2 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    This end point was not evaluated, as the resulting information would only have been needed to help confirm the dose for Stage 2 (which never opened due to the early termination of the study in Stage 1).
  • Time of Maximum Observed Plasma Concentration (Tmax) for BMS-955176-Stage 1 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    PK assessments were planned to be performed; however, it was not performed due to the early termination of the study in Stage 1.
  • Tmax for BMS-955176-Stage 2 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    This end point was not evaluated, as the resulting information would only have been needed to help confirm the dose for Stage 2 (which never opened due to the early termination of the study in Stage 1).
  • Observed Plasma Concentration at the End of a Dosing Interval (Ctau) for BMS-955176-Stage 1 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    PK assessments were planned to be performed; however, it was not performed due to the early termination of the study in Stage 1.
  • Ctau for BMS-955176-Stage 2 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    This end point was not evaluated, as the resulting information would only have been needed to help confirm the dose for Stage 2 (which never opened due to the early termination of the study in Stage 1).
  • Observed Pre-dose Plasma Concentration (C0) for BMS-955176-Stage 1 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    PK assessments were planned to be performed; however, it was not performed due to the early termination of the study in Stage 1.
  • C0 for BMS-955176-Stage 2 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    This end point was not evaluated, as the resulting information would only have been needed to help confirm the dose for Stage 2 (which never opened due to the early termination of the study in Stage 1).
  • Area Under the Concentration-time Curve in One Dosing Interval (AUC[Tau]) for BMS-955176-Stage 1 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    PK assessments were planned to be performed; however, it was not performed due to the early termination of the study in Stage 1.
  • AUC(Tau) for BMS-955176-Stage 2 [ Time Frame: Week 2 (pre-dose, 1, 2, 2.5, 3, 4, 4.5, 5, 6, 8, 12 hours post-dose and 24 hours [morning pre-dose]) ]
    This end point was not evaluated, as the resulting information would only have been needed to help confirm the dose for Stage 2 (which never opened due to the early termination of the study in Stage 1).
  • Number of Participants With Emergence of HIV Drug Resistance-Stage 1 [ Time Frame: Up to Week 96 ]
    Emergence of drug resistance was planned to be assessed using the most current version of International AIDS Society-United States of America (IAS-USA); however, it was not assessed due to the early termination of the study in Stage 1.
  • Number of Participants With Emergence of HIV Drug Resistance-Stage 2 [ Time Frame: Up to Week 96 ]
    This end point was not evaluated, as the resulting information would only have been needed to help assess the risk for Stage 2 (which never opened due to the early termination of the study in Stage 1).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
  • The antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms (TDF + ATV/r + DTG), by determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA less than 40 c/mL [ Time Frame: At Weeks 48 and 96 ]
  • The antiviral efficacy of BMS-955176 Arms, and the TDF-containing Arms, by determining the proportion of treatment-experienced subjects with plasma HIV-1 RNA less than 200 c/mL [ Time Frame: At Weeks 24,48 and 96 ]
  • The emergence of HIV drug resistance in samples selected for drug resistance testing [ Time Frame: At Weeks 24,48 and 96 ]
  • Efficacy of BMS-955176 Arms, and the TDF-containing Arms, by using the mean changes from baseline in log10 HIV-1 RNA, CD4+ T-cell counts, and percentage of CD4+ T cells [ Time Frame: At Weeks 24,48 and 96 ]
  • Safety and tolerability of BMS-955176 in treatment-experienced subjects by measuring frequency of serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation [ Time Frame: At Weeks 24,48 and 96 ]
  • Disease progression as measured by the occurrence of new Acquired immune deficiency syndrome (AIDS) defining events (CDC Class C events) [ Time Frame: At Weeks 24,48 and 96 ]
  • Area under the concentration-time curve (AUC) of BMS-955176 [ Time Frame: At Week 24 ]
  • Maximum observed concentration (Cmax) of BMS-955176 [ Time Frame: At Week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Strategy-confirming Study of BMS-955176 to Treat HIV-1 Infected Treatment-experienced Adults
Official Title  ICMJE A Phase 2b Randomized, Active-Controlled, Staged, Open-Label Trial to Investigate Safety and Efficacy of BMS-955176/GSK3532795 in Combination With Dolutegravir and Atazanavir (With or Without Ritonavir) in Treatment-Experienced HIV-1 Infected Adults
Brief Summary The purpose of this study is to evaluate whether the combination of BMS-955176 with atazanavir (ATV) [with or without ritonavir (RTV)] and dolutegravir (DTG) is efficacious, safe, and well-tolerated in HIV-1 infected treatment experienced adults.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: BMS-955176
    HIV Maturation Inhibitor
  • Drug: Atazanavir (ATV)
    Atazanavir
  • Drug: Ritonavir (RTV)
    Ritonavir
  • Drug: Dolutegravir (DTG)
    Dolutegravir
  • Drug: Tenofovir (TDF)
    Tenofovir
Study Arms  ICMJE
  • Experimental: Arm 1: BMS-955176 + ATV + RTV + DTG
    BMS-955176 at 120 mg tablet per day + Atazanavir boosted with ritonavir (ATV/r) 300/100 mg tablets per day + DTG 50 mg tablet per day, orally
    Interventions:
    • Drug: BMS-955176
    • Drug: Atazanavir (ATV)
    • Drug: Ritonavir (RTV)
    • Drug: Dolutegravir (DTG)
  • Arm 2: TDF + ATV + RTV + DTG
    TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
    Interventions:
    • Drug: Atazanavir (ATV)
    • Drug: Ritonavir (RTV)
    • Drug: Dolutegravir (DTG)
    • Drug: Tenofovir (TDF)
  • Experimental: Arm 3: BMS-955176 + ATV + DTG
    BMS-955176 at 120 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally
    Interventions:
    • Drug: BMS-955176
    • Drug: Atazanavir (ATV)
    • Drug: Dolutegravir (DTG)
  • Experimental: Arm 4: BMS-955176 + ATV + DTG
    BMS-955176 at 180 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally
    Interventions:
    • Drug: BMS-955176
    • Drug: Atazanavir (ATV)
    • Drug: Dolutegravir (DTG)
  • Arm 5: TDF + ATV + RTV + DTG
    TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally
    Interventions:
    • Drug: Atazanavir (ATV)
    • Drug: Ritonavir (RTV)
    • Drug: Dolutegravir (DTG)
    • Drug: Tenofovir (TDF)
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 Terminated
Actual Enrollment  ICMJE
 (submitted: May 17, 2018)
86
Original Estimated Enrollment  ICMJE
 (submitted: March 6, 2015)
200
Actual Study Completion Date  ICMJE June 7, 2017
Actual Primary Completion Date June 7, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men and non-pregnant women, at least 18 years of age
  • Antiretroviral treatment-experienced, defined as having documented evidence of having failed 1 or 2 regimens that include 2 or 3 classes of antiretroviral (ARV) (with or without documented resistance)
  • CD4+ T-cell count > 50 cells/mm3
  • Screening genotype/phenotype indicating susceptibility to study drugs (unboosted ATV, FC < 2.2; DTG; TDF)

Exclusion Criteria:

  • Antiretroviral treatment-experienced adults who have failed > 2 ARV regimens
  • Resistance or partial resistance to any study drug determined by tests at Screening
  • Historical or documented genotypic and/or phenotypic drug resistance testing showing certain resistance mutations to ATV, TDF, RAL, Protease Inhibitors, and certain TAMs
  • Chronic hepatitis B virus (HBV)/ hepatitis C virus (HCV)
  • Blood tests that indicate normal liver function
  • Hemoglobin < 8.0 g/dL, Platelets < 50,000 cells/mm3
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Canada,   Chile,   Colombia,   Mexico,   Peru,   Puerto Rico,   Russian Federation,   South Africa,   Taiwan,   Thailand,   United States
Removed Location Countries Brazil,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT02386098
Other Study ID Numbers  ICMJE 205892
AI468-048 ( Other Identifier: Bristol-Myers Squibb )
Has Data Monitoring Committee No
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 Not Provided
Responsible Party ViiV Healthcare
Study Sponsor  ICMJE ViiV Healthcare
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Study Director: GSK Clinical Trials ViiV Healthcare
PRS Account ViiV Healthcare
Verification Date August 2018

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