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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02386098
• Other study ID #: 205892
• Secondary ID: AI468-048
• Status: Terminated
• Phase: Phase 2
• Start date: July 8, 2015
• Est. completion date: June 7, 2017

Study information

• Verified date: August 2018
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 86
• Est. completion date: June 7, 2017
• Est. primary completion date: June 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• BMS-955176
HIV Maturation Inhibitor
• Atazanavir (ATV)
Atazanavir
• Ritonavir (RTV)
Ritonavir
• Dolutegravir (DTG)
Dolutegravir
• Tenofovir (TDF)
Tenofovir

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Córdoba
Argentina	GSK Investigational Site	Mar del Plata
Argentina	GSK Investigational Site	Rosario	Santa Fe
Australia	GSK Investigational Site	Darlinghurst	New South Wales
Australia	GSK Investigational Site	Darlinghurst, Sydney	New South Wales
Australia	GSK Investigational Site	Sydney	New South Wales
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	Winnipeg	Manitoba
Chile	GSK Investigational Site	Providencia, Santiago De Chile
Chile	GSK Investigational Site	Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Colombia	GSK Investigational Site	Barranquilla
Colombia	GSK Investigational Site	Bogota
Colombia	GSK Investigational Site	Bogotá
Colombia	GSK Investigational Site	Cali
Mexico	GSK Investigational Site	DF
Mexico	GSK Investigational Site	Distrito Federal
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Juarez	Chihuahua
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Oaxaca
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Puerto Rico	GSK Investigational Site	San Juan
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Irkutsk
Russian Federation	GSK Investigational Site	Krasnodar
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	St. Petersburg
South Africa	GSK Investigational Site	Bloemfontein	Free State
South Africa	GSK Investigational Site	Port Elizabeth	Eastern Cape
South Africa	GSK Investigational Site	Tembisa
South Africa	GSK Investigational Site	Westdene
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Taipei
Thailand	GSK Investigational Site	Bangkok
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Beverly Hills	California
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	New Haven	Connecticut
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Palm Springs	California
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
ViiV Healthcare	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Chile,  Colombia,  Mexico,  Peru,  Puerto Rico,  Russian Federation,  South Africa,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 24
Primary	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.	Week 24
Secondary	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.	Weeks 48 and 96
Secondary	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.	Weeks 48 and 96
Secondary	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.	Weeks 24, 48 and 96
Secondary	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.	Weeks 24, 48 and 96
Secondary	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.	Baseline and up to Week 72
Secondary	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.	Baseline and up to Week 96
Secondary	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.	Baseline and up to Week 72
Secondary	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.	Baseline and up to Week 96
Secondary	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.	Baseline and up to Week 72
Secondary	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.	Baseline and up to Week 96
Secondary	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.	Up to Week 96
Secondary	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.	Up to Week 96
Secondary	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.	Up to Week 96
Secondary	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.	Up to Week 96
Secondary	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.	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	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).	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	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.	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	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).	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	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.	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	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).	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	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.	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	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).	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	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.	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	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).	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	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.	Up to Week 96
Secondary	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).	Up to Week 96