HIV Attachment Inhibitor to Treat Human Immunodeficiency Virus 1 (HIV-1) Infections

Tracking Information
First Submitted Date ICMJE	June 23, 2011
First Posted Date ICMJE	June 29, 2011
Last Update Posted Date	April 6, 2018
Actual Study Start Date ICMJE	July 26, 2011
Actual Primary Completion Date	February 18, 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 28, 2011)	Proportion of subjects with plasma HIV-1 ribonucleic acid (RNA) < 50 c/mL [ Time Frame: At Week 24 ]; Frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) [ Time Frame: Up to Week 24 ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01384734 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 4, 2017)	Changes from monotherapy baseline (Monotherapy Day 1) in log10 HIV ribonucleic acid (RNA) by study day during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ]Monotherapy Substudy; Maximum decrease from monotherapy baseline in log10 plasma HIV-1 RNA during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ]Monotherapy Substudy; Proportion of subjects with plasma HIV-1 RNA < 50 c/mL at baseline (Combination Therapy Day 1) [ Time Frame: Baseline and at Monotherapy Day 7 ]Monotherapy Substudy; Frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) during monotherapy [ Time Frame: At Monotherapy Day 7 ]Monotherapy Substudy; Changes from monotherapy baseline in CD4+ and CD8+ T-cell counts and percents by study day during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ]Monotherapy Substudy; Proportion of subjects with plasma HIV-1 RNA < 50 c/mL [ Time Frame: Week 48 ]Primary Study; Frequency of SAEs and discontinuations due to AEs [ Time Frame: Week 48 ]Primary Study; Frequency of SAEs and discontinuations due to AE [ Time Frame: Week 96 ]Primary Study; Proportion of subjects with plasma HIV-1 RNA < 50 c/mL. [ Time Frame: Week 96 ]Primary Study; Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 24 ]Primary Study; Changes from baseline in CD4+ T-cell count. [ Time Frame: Baseline and Week 48 ]Primary Study; Changes from baseline in CD4+ T-cell count, [ Time Frame: Baseline and Week 96 ]Primary Study; Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 24 ]Primary Study; Frequency of newly-emergent genotypic substitutions among subjects with virologic failure. [ Time Frame: Week 48 ]Primary Study; Frequency of newly-emergent genotypic substitutions among subjects with virologic failure, [ Time Frame: Week 96 ]Primary Study
Original Secondary Outcome Measures ICMJE; (submitted: June 28, 2011)	Changes from monotherapy baseline (Monotherapy Day 1) in log10 HIV ribonucleic acid (RNA) by study day during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ]Monotherapy Substudy; Maximum decrease from monotherapy baseline in log10 plasma HIV-1 RNA during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ]Monotherapy Substudy; Proportion of subjects with plasma HIV-1 RNA < 50 c/mL at baseline (Combination Therapy Day 1) [ Time Frame: Baseline and at Monotherapy Day 7 ]Monotherapy Substudy; Frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) during monotherapy [ Time Frame: At Monotherapy Day 7 ]Monotherapy Substudy; Changes from monotherapy baseline in CD4+ and CD8+ T-cell counts and percents by study day during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ]Monotherapy Substudy; Proportion of subjects with plasma HIV-1 RNA < 50 c/mL [ Time Frame: Week 48 ]Primary Study; Proportion of subjects with plasma HIV-1 RNA < 50 c/mL [ Time Frame: Week 96 ]Primary Study; Frequency of SAEs and discontinuations due to AEs [ Time Frame: Week 48 ]Primary Study; Frequency of SAEs and discontinuations due to AEs [ Time Frame: Week 96 ]Primary Study; Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 24 ]Primary Study; Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 48 ]Primary Study; Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 96 ]Primary Study; Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 24 ]Primary Study; Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 48 ]Primary Study; Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 96 ]Primary Study
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	HIV Attachment Inhibitor to Treat Human Immunodeficiency Virus 1 (HIV-1) Infections
Official Title ICMJE	A Phase IIb Randomized, Controlled, Partially-Blinded Trial to Investigate Safety, Efficacy and Dose-Response of BMS-663068 in Treatment-experienced HIV-1 Subjects, Followed by an Open-Label Period on the Recommended Dose
Brief Summary	The purpose of this study is to assess the safety, efficacy, tolerability and pharmacokinetics of four doses of BMS-663068 with Raltegravir (RAL) + Tenofovir Disoproxil Fumarate (TDF). At least 1 dose of BMS-663068 can be identified which is safe, well tolerated, and efficacious when combined with RAL + TDF for treatment-experienced HIV-1 infected subjects. PHENOSENSE® is a registered trademark of Monogram Biosciences.
Detailed Description	Masking: Double-blind for BMS-6630368 treatment groups until the Week 24 Primary Endpoint analysis, then open label. The reference groups is all open-label. Arms: 5 (4 BMS-663068 treatment groups and 1 reference group) Intervention Model: Parallel (with unblinding after the Week 24 primary endpoint analysis)
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Infection, Human Immunodeficiency Virus
Intervention ICMJE	Drug: BMS-663068 400 mg Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose; Drug: BMS-663068 800 mg Tablets, Oral, 800 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose; Drug: BMS-663068 600 mg Tablets, Oral, 600 mg, once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose; Drug: BMS-663068 1200 mg Tablets, Oral, 1200 mg, once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose; Drug: Raltegravir 400 mg Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose; Drug: Tenofovir 300 mg Tablets, Oral, 300 mg, Once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose; Drug: Ritonavir 100 mg Tablets, Oral, 100 mg, Once daily, 96 weeks; Drug: Atazanavir 300 mg Capsules, Oral, 300 mg, Once daily, 96 weeks
Study Arms	Experimental: Arm A: BMS-663068 (400mg) + Raltegravir + Tenofovir Treatment Group 1 Interventions: Drug: BMS-663068 400 mg Drug: Raltegravir 400 mg Drug: Tenofovir 300 mg; Experimental: Arm B: BMS-663068 (800 mg) + Raltegravir + Tenofovir Treatment Group 2 Interventions: Drug: BMS-663068 800 mg Drug: Raltegravir 400 mg Drug: Tenofovir 300 mg; Experimental: Arm C: BMS-663068 (600 mg) + Raltegravir + Tenofovir Treatment Group 3 Interventions: Drug: BMS-663068 600 mg Drug: Raltegravir 400 mg Drug: Tenofovir 300 mg; Experimental: Arm D: BMS-663068 (1200 mg) + Raltegravir + Tenofovir Treatment Group 4 Interventions: Drug: BMS-663068 1200 mg Drug: Raltegravir 400 mg Drug: Tenofovir 300 mg; Active Comparator: Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir Treatment Group 1 (reference arm) Interventions: Drug: Raltegravir 400 mg Drug: Tenofovir 300 mg Drug: Ritonavir 100 mg Drug: Atazanavir 300 mg
Publications *	Landry I, Zhu L, Abu Tarif M, Hruska M, Sadler BM, Pitsiu M, Joshi S, Hanna GJ, Lataillade M, Boulton DW, Bertz RJ. Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2782-9. doi: 10.1128/AAC.02503-15. Print 2016 May.; Lalezari JP, Latiff GH, Brinson C, Echevarría J, Treviño-Pérez S, Bogner JR, Thompson M, Fourie J, Sussmann Pena OA, Mendo Urbina FC, Martins M, Diaconescu IG, Stock DA, Joshi SR, Hanna GJ, Lataillade M; AI438011 study team. Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial. Lancet HIV. 2015 Oct;2(10):e427-37. doi: 10.1016/S2352-3018(15)00177-0. Epub 2015 Sep 1.; Zhou N, Nowicka-Sans B, McAuliffe B, Ray N, Eggers B, Fang H, Fan L, Healy M, Langley DR, Hwang C, Lataillade M, Hanna GJ, Krystal M. Genotypic correlates of susceptibility to HIV-1 attachment inhibitor BMS-626529, the active agent of the prodrug BMS-663068. J Antimicrob Chemother. 2014 Mar;69(3):573-81. doi: 10.1093/jac/dkt412. Epub 2013 Oct 14.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 1, 2017)	254
Original Estimated Enrollment ICMJE; (submitted: June 28, 2011)	250
Actual Study Completion Date	May 12, 2017
Actual Primary Completion Date	February 18, 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Plasma HIV-1 RNA ≥ 1000 copies/ml at Screening; Treatment experience with antiretroviral therapies (excluding integrase inhibitors); Screening PHENOSENSE Entry indicating BMS-626529 inhibitory concentration (IC)50 < 0.1 μM; Cluster of differentiation (CD)4+ T-cell count > 50 cells/mm3 Exclusion Criteria: History (or evidence at Screening) of genotypic resistance to any component of the study regimen [ Tenofovir Disoproxil Fumarate (TDF), Atazanavir (ATV), Raltegravir (RAL)]; Certain laboratory and electrocardiogram (ECG) values
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Colombia, Germany, Mexico, Peru, Romania, Russian Federation, South Africa, Spain, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01384734
Other Study ID Numbers ICMJE	205889; AI438-011 ( Other Identifier: Bristol-Myers Squibb )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	ViiV Healthcare
Study Sponsor ICMJE	ViiV Healthcare
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: GSK Clinical Trials ViiV Healthcare
PRS Account	ViiV Healthcare
Verification Date	April 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP