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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02386098




Registration number
NCT02386098
Ethics application status
Date submitted
6/03/2015
Date registered
11/03/2015
Date last updated
20/08/2018

Titles & IDs
Public title
Strategy-confirming Study of BMS-955176 to Treat HIV-1 Infected Treatment-experienced Adults
Scientific 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
Secondary ID [1] 0 0
AI468-048
Secondary ID [2] 0 0
205892
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BMS-955176
Treatment: Drugs - Atazanavir (ATV)
Treatment: Drugs - Ritonavir (RTV)
Treatment: Drugs - Dolutegravir (DTG)
Treatment: Drugs - Tenofovir (TDF)

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

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

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

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

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


Treatment: Drugs: BMS-955176
HIV Maturation Inhibitor

Treatment: Drugs: Atazanavir (ATV)
Atazanavir

Treatment: Drugs: Ritonavir (RTV)
Ritonavir

Treatment: Drugs: Dolutegravir (DTG)
Dolutegravir

Treatment: Drugs: Tenofovir (TDF)
Tenofovir

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Week 24
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Week 24
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Weeks 48 and 96
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Weeks 48 and 96
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Weeks 24, 48 and 96
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Weeks 24, 48 and 96
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline and up to Week 72
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline and up to Week 96
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Baseline and up to Week 72
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline and up to Week 96
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline and up to Week 72
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline and up to Week 96
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Up to Week 96
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Up to Week 96
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Up to Week 96
Secondary outcome [14] 0 0
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.
Timepoint [14] 0 0
Up to Week 96
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
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])
Secondary outcome [16] 0 0
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).
Timepoint [16] 0 0
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])
Secondary outcome [17] 0 0
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.
Timepoint [17] 0 0
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])
Secondary outcome [18] 0 0
Tmax 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).
Timepoint [18] 0 0
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])
Secondary outcome [19] 0 0
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.
Timepoint [19] 0 0
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])
Secondary outcome [20] 0 0
Ctau 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).
Timepoint [20] 0 0
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])
Secondary outcome [21] 0 0
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.
Timepoint [21] 0 0
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])
Secondary outcome [22] 0 0
C0 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).
Timepoint [22] 0 0
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])
Secondary outcome [23] 0 0
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.
Timepoint [23] 0 0
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])
Secondary outcome [24] 0 0
AUC(Tau) 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).
Timepoint [24] 0 0
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])
Secondary outcome [25] 0 0
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.
Timepoint [25] 0 0
Up to Week 96
Secondary outcome [26] 0 0
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).
Timepoint [26] 0 0
Up to Week 96

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst, Sydney
Recruitment hospital [2] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [3] 0 0
GSK Investigational Site - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2010 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Oklahoma
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Santa Fe
Country [11] 0 0
Argentina
State/province [11] 0 0
Córdoba
Country [12] 0 0
Argentina
State/province [12] 0 0
Mar del Plata
Country [13] 0 0
Canada
State/province [13] 0 0
British Columbia
Country [14] 0 0
Canada
State/province [14] 0 0
Manitoba
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Chile
State/province [17] 0 0
Región Metro De Santiago
Country [18] 0 0
Chile
State/province [18] 0 0
Providencia, Santiago De Chile
Country [19] 0 0
Chile
State/province [19] 0 0
Santiago
Country [20] 0 0
Colombia
State/province [20] 0 0
Barranquilla
Country [21] 0 0
Colombia
State/province [21] 0 0
Bogota
Country [22] 0 0
Colombia
State/province [22] 0 0
Bogotá
Country [23] 0 0
Colombia
State/province [23] 0 0
Cali
Country [24] 0 0
Mexico
State/province [24] 0 0
Chihuahua
Country [25] 0 0
Mexico
State/province [25] 0 0
Jalisco
Country [26] 0 0
Mexico
State/province [26] 0 0
DF
Country [27] 0 0
Mexico
State/province [27] 0 0
Distrito Federal
Country [28] 0 0
Mexico
State/province [28] 0 0
Mexico City
Country [29] 0 0
Mexico
State/province [29] 0 0
Oaxaca
Country [30] 0 0
Peru
State/province [30] 0 0
Lima
Country [31] 0 0
Puerto Rico
State/province [31] 0 0
San Juan
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Ekaterinburg
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Irkutsk
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Krasnodar
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Moscow
Country [36] 0 0
Russian Federation
State/province [36] 0 0
St. Petersburg
Country [37] 0 0
South Africa
State/province [37] 0 0
Eastern Cape
Country [38] 0 0
South Africa
State/province [38] 0 0
Free State
Country [39] 0 0
South Africa
State/province [39] 0 0
Tembisa
Country [40] 0 0
South Africa
State/province [40] 0 0
Westdene
Country [41] 0 0
Taiwan
State/province [41] 0 0
Kaohsiung
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taipei
Country [43] 0 0
Thailand
State/province [43] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ViiV Healthcare
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02386098
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02386098