Dose-finding Study of BMS-955176 to Treat HIV-1 Infected Treatment-naive Adults

Infection, Human Immunodeficiency Virus Clinical Trial

Official title:

A Phase 2b Randomized, Active-Controlled, Double-Blind Trial to Investigate Safety, Efficacy, and Dose-response of BMS-955176, Given on a Backbone of Tenofovir/Emtricitabine, in Treatment-Naive HIV-1 Infected Adults

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02415595
• Other study ID #: 205891
• Secondary ID: 2013-005487-26AI
• Status: Terminated
• Phase: Phase 2
• Start date: May 12, 2015
• Est. completion date: August 21, 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 find at least one dose of BMS-955176 that will be safe, effective and tolerable for HIV-1 infected treatment naive adults.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 210
• Est. completion date: August 21, 2017
• Est. primary completion date: May 26, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

• Men and non-pregnant women, at least 18 years of age

• Antiretroviral treatment-naïve; defined as no current or previous exposure to > 1 week of an antiretroviral drug

• Plasma HIV-1 RNA = 1000 copies/mL

• CD4 T-cell count > 200 cells/mm3

Exclusion Criteria:

• Resistance or partial resistance to any study drug determined by tests at Screening

• Current or historical genotypic and/or phenotypic drug resistance testing showing certain resistance mutations to EFV, TDF, FTC, Protease Inhibitors

• 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

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes
• Infection, Human Immunodeficiency Virus

Intervention

Drug:
• BMS-955176
HIV Maturation Inhibitor
• EFV
EFV
• TDF/FTC
TDF/FTC

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Córdoba
Argentina	GSK Investigational Site	Rosario	Santa Fe
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Winnipeg	Manitoba
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago
Chile	GSK Investigational Site	Santiago
France	GSK Investigational Site	Le Kremlin-Bicêtre
France	GSK Investigational Site	Lyon cedex 04
France	GSK Investigational Site	Nantes
France	GSK Investigational Site	Nice
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Paris Cedex 10
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dortmund
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Italy	GSK Investigational Site	Bergamo	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Monza	Lombardia
Mexico	GSK Investigational Site	DF
Mexico	GSK Investigational Site	Durango
Mexico	GSK Investigational Site	Fracc. Las Americas	Aguascalientes
Mexico	GSK Investigational Site	León	Guanajuato
Mexico	GSK Investigational Site	Mexico City
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Szczecin
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wroclaw
South Africa	GSK Investigational Site	Bloemfontein	Free State
Spain	GSK Investigational Site	Alcala de Henares
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Santiago de Compostela
United Kingdom	GSK Investigational Site	Edinburgh	Midlothian
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Tooting, London
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Beverly Hills	California
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	DeLand	Florida
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Santa Fe	New Mexico
United States	GSK Investigational Site	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
ViiV Healthcare	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  France,  Germany,  Italy,  Mexico,  Poland,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <40 Copies Per Milliliter (c/mL) at Week 24 Using Food and Drug Administration (FDA) Snapshot Algorithm	Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV 1 RNA <40 c/mL at Week 24 using the FDA snapshot algorithm. This 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 mITT Population, which comprised of randomized participants who received at least 1 dose of BMS-955176/GSK3532795 or EFV.	Week 24
Secondary	Number of Participants With Plasma HIV-1 RNA < 40 c/mL at Weeks 48 and 96 Using FDA Snapshot Algorithm	Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV 1 RNA <40 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response. The analysis was performed 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 (10 October 2016). The data was not collected for Week 96 analysis; as the study was terminated early. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).	Weeks 48 and 96
Secondary	Number of Participants With Plasma HIV-1 RNA < 200 c/mL at Week 24 Using FDA Snapshot Algorithm	Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV-1 RNA <200 c/mL at Week 24 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response.	Week 24
Secondary	Number of Participants With Plasma HIV-1 RNA < 200 c/mL at Weeks 48 and 96	Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV-1 RNA <200 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response. The analysis was performed 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 (10 October 2016). The data was not collected for Week 96 analysis; as the study was terminated early. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).	Weeks 48 and 96
Secondary	Number of Participants With Newly Emergent Genotypic Resistance Using All On-treatment Isolates	The emergence of genotypic resistance among samples selected for drug resistance testing were assessed by searching for all reverse transcriptase substitutions and protease inhibitor substitutions listed in the International Acquired Immunodeficiency Syndrome (AIDS) Society-United States of America (IAS-USA) list of HIV-1 drug resistance mutations. The outcome was originally designed to be assessed up to 96 weeks of treatment, but it was analyzed up to Week 24 as the study was terminated early. The emergence of genotypic resistance is presented for participants in the mITT Population who had Baseline and on-treatment genotypic resistance testing and who had successful sequencing.	Week 24
Secondary	Number of Participants With Newly Emergent Phenotypic Resistance Using All On-treatment Isolates	Phenotypic resistance to a drug is defined as a fold change (i.e., ratio of the 50% inhibitory concentration (IC50) of the clinical isolate to the IC50 of the reference strain) which is greater than the cut-off for reduced susceptibility. Emergent phenotypic resistance to BMS-955176/GSK3532795 was defined as a Baseline fold change IC50<= 3 and an on-treatment fold change IC50>3. The number of participants with newly emergent phenotypic resistance is presented for participants in the mITT Population who had Baseline and on-treatment phenotypic resistance testing. The outcome was originally designed to be assessed up to 96 weeks of treatment, but it was analyzed up to Week 24 as the study was terminated early.	Week 24
Secondary	Change From Baseline in Logarithm to the Base 10 (log10) HIV-1 RNA Over Time	Blood samples were collected for analysis of HIV-1 RNA. Values obtained at Day 1 were considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus 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). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.	Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Secondary	Change From Baseline in Cluster of Differentiation (CD)4+ Thymus (T)-Cell Counts Over Time	CD4+ T-cell counts was assessed using flow cytometry. Values obtained at Day 1 were considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Change from Baseline in CD4+T- cell counts 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). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.	Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Secondary	Change From Baseline in the Percentage of CD4+ T-cells Over Time	CD4+ T-cell counts overall was assessed using flow cytometry. Values obtained at Day 1 were considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Change from Baseline in percentage of CD4+T- cell counts 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). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.	Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Secondary	Number of Participants With Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation (AELD)	Any untoward medical occurrence that at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE. Number of participants with SAEs and AELDs is summarized.	Up to Week 96
Secondary	Number of Participants With at Least One Centers for Disease Control (CDC) Class C Events	The occurrence of new AIDS defining events that is CDC class C events is presented.	Up to Week 96
Secondary	Maximum Observed Plasma Concentration (Cmax), Observed Pre-dose Plasma Concentration (C0) and Observed Plasma Concentration at the End of a Dosing Interval (Ctau) of BMS-955176/GSK3532795	Serial blood samples were collected at indicated time points for intensive pharmacokinetic (PK) assessment. The PK assessments were performed on evaluable PK Population, a sub-population which included all treated participants who had adequate PK profiles.	Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Secondary	Time of Maximum Observed Plasma Concentration (Tmax) of BMS-955176/GSK3532795	Serial blood samples were collected at indicated time points for intensive PK assessment.	Pre-dose (morning) and 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Secondary	Area Under the Concentration-time Curve in One Dosing Interval (AUC [Tau]) of BMS-955176/GSK3532795	Serial blood samples were collected at indicated time points for intensive PK assessment.	Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)

External Links

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