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

Primary Purpose

HIV Infections

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

BMS-955176

Atazanavir (ATV)

Ritonavir (RTV)

Dolutegravir (DTG)

Tenofovir (TDF)

About this trial

This is an interventional treatment trial for HIV Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Other

Experimental

Other

Arm Label

Arm 1: BMS-955176 + ATV + RTV + DTG

Arm 2: TDF + ATV + RTV + DTG

Arm 3: BMS-955176 + ATV + DTG

Arm 4: BMS-955176 + ATV + DTG

Arm 5: TDF + ATV + RTV + DTG

Arm Description

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

TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally

BMS-955176 at 120 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally

BMS-955176 at 180 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally

TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally

Outcomes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Observed Plasma Concentration at the End of a Dosing Interval (Ctau) for BMS-955176-Stage 1

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

Observed Pre-dose Plasma Concentration (C0) for BMS-955176-Stage 1

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

Area Under the Concentration-time Curve in One Dosing Interval (AUC[Tau]) for BMS-955176-Stage 1

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

Number of Participants With Emergence of HIV Drug Resistance-Stage 1

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

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).

Full Information

NCT ID

NCT02386098

First Posted

March 6, 2015

Last Updated

August 17, 2018

Sponsor

ViiV Healthcare

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT02386098

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Terminated

Why Stopped

GI Intolerability

Study Start Date

July 8, 2015 (Actual)

Primary Completion Date

June 7, 2017 (Actual)

Study Completion Date

June 7, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ViiV Healthcare

Collaborators

GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

86 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1: BMS-955176 + ATV + RTV + DTG

Arm Type

Experimental

Arm Description

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

Arm Title

Arm 2: TDF + ATV + RTV + DTG

Arm Type

Other

Arm Description

TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally

Arm Title

Arm 3: BMS-955176 + ATV + DTG

Arm Type

Experimental

Arm Description

BMS-955176 at 120 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally

Arm Title

Arm 4: BMS-955176 + ATV + DTG

Arm Type

Experimental

Arm Description

BMS-955176 at 180 mg tablet per day + ATV at 400 mg tablet per day + DTG at 50 mg tablet per day, orally

Arm Title

Arm 5: TDF + ATV + RTV + DTG

Arm Type

Other

Arm Description

TDF 300 mg tablet per day + ATV/r at 300/100 mg tablets per day + DTG 50 mg per day, orally

Intervention Type

Drug

Intervention Name(s)

BMS-955176

Intervention Description

HIV Maturation Inhibitor

Intervention Type

Drug

Intervention Name(s)

Atazanavir (ATV)

Intervention Description

Atazanavir

Intervention Type

Drug

Intervention Name(s)

Ritonavir (RTV)

Intervention Description

Ritonavir

Intervention Type

Drug

Intervention Name(s)

Dolutegravir (DTG)

Intervention Description

Dolutegravir

Intervention Type

Drug

Intervention Name(s)

Tenofovir (TDF)

Intervention Description

Tenofovir

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Week 24

Title

Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Week 24-Stage 2

Description

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.

Time Frame

Week 24

Secondary Outcome Measure Information:

Title

Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Weeks 48 and 96-Stage 1

Description

Time Frame

Weeks 48 and 96

Title

Percentage of Participants With Plasma HIV-1 RNA <40 c/mL at Weeks 48 and 96-Stage 2

Description

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.

Time Frame

Weeks 48 and 96

Title

Percentage of Participants With HIV-1 RNA <200 c/mL at Weeks 24, 48 and 96-Stage 1

Description

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.

Time Frame

Weeks 24, 48 and 96

Title

Percentage of Participants With HIV-1 RNA <200 c/mL at Weeks 24, 48 and 96-Stage 2

Description

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.

Time Frame

Weeks 24, 48 and 96

Title

Change From Baseline in Logarithm to the Base 10 (log10) HIV-1 RNA Over Time-Stage 1

Description

Time Frame

Baseline and up to Week 72

Title

Change From Baseline in log10 HIV-1 RNA Over Time-Stage 2

Description

This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.

Time Frame

Baseline and up to Week 96

Title

Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Count Over Time-Stage 1

Description

Time Frame

Baseline and up to Week 72

Title

Change From Baseline in CD4+ Cell Count Over Time-Stage 2

Description

This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.

Time Frame

Baseline and up to Week 96

Title

Change From Baseline in Percentage of CD4+ Cells Over Time-Stage 1

Description

Time Frame

Baseline and up to Week 72

Title

Change From Baseline in Percentage of CD4+ Cells Over Time-Stage 2

Description

This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.

Time Frame

Baseline and up to Week 96

Title

Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Stage 1

Description

Time Frame

Up to Week 96

Title

Number of Participants With SAEs and AELDs-Stage 2

Description

This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.

Time Frame

Up to Week 96

Title

Number of Participants With Occurrence of New Acquired Immunodeficiency Syndrome (AIDS) Defining Events-Stage 1

Description

The occurrence of new AIDS defining events that is, Centers for Disease Control (CDC) Class C events in participants is presented.

Time Frame

Up to Week 96

Title

Number of Participants With Occurrence of New AIDS Defining Events-Stage 2

Description

This end point was not evaluated in Stage 2 due to early termination of the study during Stage 1.

Time Frame

Up to Week 96

Title

Maximum Observed Concentration (Cmax) for BMS-955176-Stage 1

Description

Time Frame