Clinical Trials

MainTitle

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

This study has been terminated
( GI Intolerability )

Sponsor
ViiV Healthcare

Collaborator
GlaxoSmithKline

Information provided by (Responsible Party)
ViiV Healthcare
ClinicalTrials.gov Identifier
NCT02386098

First received: March 6, 2015
Last updated: May 17, 2018
Last Verified: May 2018
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infections

Drug : BMS-955176
Drug : Atazanavir (ATV)
Drug : Ritonavir (RTV)
Drug : Dolutegravir (DTG)
Drug : Tenofovir (TDF)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2b Randomized, Active-Controlled, Staged, Open-label Trial to Investigate Safety and Efficacy of BMS-955176 in Combination With Dolutegravir and Atazanavir (With or Without Ritonavir) in Treatment-Experienced HIV-1 Infected Adults

Further study details as provided by ViiV Healthcare:

Primary Outcome Measures

  • 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.
Secondary Outcome Measures:
  • 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 Treated 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 Treated 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]) ]
    Blood samples were planned to be collected for intensive pharmacokinetic (PK) assessment at the indicated time points. Intensive PK sampling was planned to begin with a morning pre-dose sampling prior to administration of morning dose of study treatment on the day of visit and 24 hours after the morning dose of study treatment taken a day prior to the visit. The PK assessments were planned to be performed on PK Population, which comprised of all treated participants who had any available concentration-time data. This end point was not evaluated due to early termination of the study during 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]) ]
    Blood samples were planned to be collected for intensive pharmacokinetic (PK) assessment at the indicated time points. Intensive PK sampling was planned to begin with a morning pre-dose sampling prior to administration of morning dose of study treatment on the day of visit and 24 hours after the morning dose of study treatment taken a day prior to the visit. The PK assessments were planned to be performed on PK Population, which comprised of all treated participants who had any available concentration-time data. This end point was not evaluated due to early termination of the study during 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]) ]
    Blood samples were planned to be collected for intensive PK assessment at the indicated time points; however, the end points were not analyzed due to early termination of study during Stage 1.
  • Time of maximum observed plasma concentration (Tmax) for BMS-955176 [ 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]) ]
    Blood samples were planned to be collected for intensive PK assessment at the indicated time points; however, the end points were not analyzed due to early termination of study during 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]) ]
    Blood samples were planned to be collected for intensive PK assessment at the indicated time points; however, the end points were not analyzed due to early termination of study during 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]) ]
    Blood samples were planned to be collected for intensive PK assessment at the indicated time points; however, the end points were not analyzed due to early termination of study during 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]) ]
    Blood samples were planned to be collected for intensive PK assessment at the indicated time points; however, the end points were not analyzed due to early termination of study during Stage 1.
  • Observed pre-dose plasma concentration (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]) ]
    Blood samples were planned to be collected for intensive PK assessment at the indicated time points; however, the end points were not analyzed due to early termination of study during Stage 1.
  • Area under the concentration-time curve in one dosing interval (AUC[tau]) for BMS-955176-Stages 1 and 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]) ]
    Blood samples were planned to be collected for intensive PK assessment at the indicated time points; however, the end points were not analyzed due to early termination of study during Stage 1.
  • Area under the concentration-time curve in one dosing interval (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]) ]
    Blood samples were planned to be collected for intensive PK assessment at the indicated time points; however, the end points were not analyzed due to early termination of study during 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 performed due to early termination of the study during Stage 1.
  • Number of participants with newly-emergent genotypic substitutions-Stage 2 [ Time Frame: Up to Week 96 ]
    Emergence of drug resistance was planned to be assessed using the most current version of IAS-USA; however it was not performed due to early termination of the study during Stage 1.

Enrollment: 86
Study Start Date: July 8, 2015
Study Completion Date: June 7, 2017
Estimated Primary Completion Date: June 7, 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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
Drug: BMS-955176

HIV Maturation Inhibitor

Drug: Atazanavir (ATV)

Atazanavir

Drug: Ritonavir (RTV)

Ritonavir

Drug: Dolutegravir (DTG)

Dolutegravir

Other: 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
Drug: Atazanavir (ATV)

Atazanavir

Drug: Ritonavir (RTV)

Ritonavir

Drug: Dolutegravir (DTG)

Dolutegravir

Drug: Tenofovir (TDF)

Tenofovir

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
Drug: BMS-955176

HIV Maturation Inhibitor

Drug: Atazanavir (ATV)

Atazanavir

Drug: Dolutegravir (DTG)

Dolutegravir

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
Drug: BMS-955176

HIV Maturation Inhibitor

Drug: Atazanavir (ATV)

Atazanavir

Drug: Dolutegravir (DTG)

Dolutegravir

Other: 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
Drug: Atazanavir (ATV)

Atazanavir

Drug: Ritonavir (RTV)

Ritonavir

Drug: Dolutegravir (DTG)

Dolutegravir

Drug: Tenofovir (TDF)

Tenofovir

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02386098

Locations

United States, California
GSK Investigational Site
Beverly Hills, California, United States, 90211
GSK Investigational Site
Los Angeles, California, United States, 90027
GSK Investigational Site
Palm Springs, California, United States, 92262
United States, Connecticut
GSK Investigational Site
New Haven, Connecticut, United States, 06520
United States, Florida
GSK Investigational Site
DeLand, Florida, United States, 32720
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33308
GSK Investigational Site
Orlando, Florida, United States, 32804
GSK Investigational Site
Tampa, Florida, United States, 33614
GSK Investigational Site
West Palm Beach, Florida, United States, 33401
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30312
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
United States, New York
GSK Investigational Site
Bronx, New York, United States, 10467
GSK Investigational Site
New York, New York, United States, 10029
United States, Oklahoma
GSK Investigational Site
Tulsa, Oklahoma, United States, 74135
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78705
GSK Investigational Site
Dallas, Texas, United States, 75246
Argentina
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1405CKC
GSK Investigational Site
Rosario, Santa Fe, Argentina, 2000
GSK Investigational Site
Buenos Aires, Argentina, 1141
GSK Investigational Site
Buenos Aires, Argentina, 1202
GSK Investigational Site
Córdoba, Argentina, X5000JJS
GSK Investigational Site
Mar del Plata, Argentina, B7600FZN
Australia
GSK Investigational Site
Darlinghurst, Sydney, New South Wales, Australia, 2010
GSK Investigational Site
Darlinghurst, New South Wales, Australia, 2010
GSK Investigational Site
Sydney, New South Wales, Australia, 2010
Canada
GSK Investigational Site
Vancouver, British Columbia, Canada, V6Z 1Y6
GSK Investigational Site
Vancouver, British Columbia, Canada, V6Z 2C7
GSK Investigational Site
Winnipeg, Manitoba, Canada, R3A 1R9
GSK Investigational Site
Toronto, Ontario, Canada, M4N 3M5
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2N2
GSK Investigational Site
Montreal, Quebec, Canada, H2L 4P9
GSK Investigational Site
Montreal, Quebec, Canada, H2L 5B1
GSK Investigational Site
Montreal, Quebec, Canada, H4A 3J1
Chile
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 8330074
GSK Investigational Site
Providencia, Santiago De Chile, Chile, 7500922
GSK Investigational Site
Santiago, Chile, 8360159
Colombia
GSK Investigational Site
Barranquilla, Colombia
GSK Investigational Site
Bogota, Colombia, 111311
GSK Investigational Site
Bogotá, Colombia
GSK Investigational Site
Cali, Colombia
Mexico
GSK Investigational Site
Juarez, Chihuahua, Mexico, 32330
GSK Investigational Site
Guadalajara, Jalisco, Mexico, 44280
GSK Investigational Site
DF, Mexico, 14000
GSK Investigational Site
Distrito Federal, Mexico, 03720
GSK Investigational Site
Mexico City, Mexico, 06700
GSK Investigational Site
Mexico City, Mexico, CP 14080
GSK Investigational Site
Oaxaca, Mexico, 68000
Peru
GSK Investigational Site
Lima, Peru, 1
GSK Investigational Site
Lima, Peru, Lima 11
GSK Investigational Site
Lima, Peru, Lima 14
GSK Investigational Site
Lima, Peru, Lima 31
Puerto Rico
GSK Investigational Site
San Juan, Puerto Rico, 00909-1711
Russian Federation
GSK Investigational Site
Ekaterinburg, Russian Federation, 620102
GSK Investigational Site
Irkutsk, Russian Federation, 664035
GSK Investigational Site
Krasnodar, Russian Federation, 350015
GSK Investigational Site
Moscow, Russian Federation, 105275
GSK Investigational Site
St. Petersburg, Russian Federation, 190103
South Africa
GSK Investigational Site
Port Elizabeth, Eastern Cape, South Africa, 6001
GSK Investigational Site
Bloemfontein, Free State, South Africa, 9301
GSK Investigational Site
Tembisa, South Africa, 1632
GSK Investigational Site
Westdene, South Africa, 2092
Taiwan
GSK Investigational Site
Kaohsiung, Taiwan, 81346
GSK Investigational Site
Taipei, Taiwan, 100
Thailand
GSK Investigational Site
Bangkok, Thailand, 10330

Sponsors and Collaborators

ViiV Healthcare
GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials ViiV Healthcare
More Information

More Information


Responsible Party: ViiV Healthcare  
ClinicalTrials.gov Identifier: NCT02386098   History of Changes  
Other Study ID Numbers: 205892  
  AI468-048  
Study First Received: March 6, 2015  
Last Updated: May 17, 2018  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
HIV Infections
Ritonavir
Atazanavir Sulfate
Tenofovir
Dolutegravir

ClinicalTrials.gov processed this data on July 19, 2018
This information is provided by ClinicalTrials.gov.