Trial Outcomes & Findings for Dose-finding Study of BMS-955176 to Treat HIV-1 Infected Treatment-naive Adults (NCT NCT02415595)

This study was originally designed for 96 weeks of treatment in treatment naïve human immunodeficiency virus-1 (HIV-1) infected adults; however, it was terminated early due to gastrointestinal intolerability and treatment emergent resistance. The study was conducted at 58 centers in 12 countries.

A total of 305 participants were screened, of which 210 were randomized to 1 of 4 treatment arms. Of 210 participants, only 206 received study treatment. Four participants were randomized but not treated as: 2 participants were randomized in error, 1 participant was lost to follow-up and 1 participant withdrew consent.

Treated Subjects Population, also known as the modified intent-to-treat (mITT) population, comprised of all subjects who received at least one dose of study treatment, was used to present baseline characteristics

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.

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).

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.

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).

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.

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.

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.

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.

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.

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.

The occurrence of new AIDS defining events that is CDC class C events is presented.

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.

Serial blood samples were collected at indicated time points for intensive PK assessment.

Serial blood samples were collected at indicated time points for intensive PK assessment.