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

Purpose

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.

Condition	Intervention	Phase
Human Immunodeficiency Virus-1	Drug: BMS-663068 Drug: Raltegravir Drug: Tenofovir Drug: Ritonavir Drug: Atazanavir	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Tenofovir Ritonavir Atazanavir Tenofovir Disoproxil Fumarate Atazanavir sulfate Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Proportion of subjects with plasma HIV-1 ribonucleic acid (RNA) < 50 c/mL [ Time Frame: At Week 24 ] [ Designated as safety issue: No ]
Frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) [ Time Frame: Up to Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
Monotherapy Substudy
Maximum decrease from monotherapy baseline in log10 plasma HIV-1 RNA during monotherapy [ Time Frame: Baseline and at Monotherapy Day 7 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Monotherapy Substudy
Frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) during monotherapy [ Time Frame: At Monotherapy Day 7 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
Monotherapy Substudy
Proportion of subjects with plasma HIV-1 RNA < 50 c/mL [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Primary Study
Proportion of subjects with plasma HIV-1 RNA < 50 c/mL [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
Primary Study
Frequency of SAEs and discontinuations due to AEs [ Time Frame: Week 48 ] [ Designated as safety issue: Yes ]
Primary Study
Frequency of SAEs and discontinuations due to AEs [ Time Frame: Week 96 ] [ Designated as safety issue: Yes ]
Primary Study
Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
Primary Study
Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
Primary Study
Changes from baseline in CD4+ T-cell count [ Time Frame: Baseline and Week 96 ] [ Designated as safety issue: No ]
Primary Study
Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Primary Study
Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
Primary Study
Frequency of newly-emergent genotypic substitutions among subjects with virologic failure [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
Primary Study


Estimated Enrollment:	250
Study Start Date:	July 2011
Estimated Study Completion Date:	September 2016
Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm A: BMS-663068 + Raltegravir + Tenofovir Treatment Group 1	Drug: BMS-663068 Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Drug: Raltegravir Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Other Name: Isentress Drug: Tenofovir Tablets, Oral, 300 mg, Once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Other Name: Viread
Experimental: Arm B: BMS-663068 + Raltegravir + Tenofovir Treatment Group 2	Drug: BMS-663068 Tablets, Oral, 800 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Drug: Raltegravir Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Other Name: Isentress Drug: Tenofovir Tablets, Oral, 300 mg, Once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Other Name: Viread
Experimental: Arm C: BMS-663068 + Raltegravir + Tenofovir Treatment Group 3	Drug: BMS-663068 Tablets, Oral, 600 mg, once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Drug: Raltegravir Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Other Name: Isentress Drug: Tenofovir Tablets, Oral, 300 mg, Once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Other Name: Viread
Experimental: Arm D: BMS-663068 + Raltegravir + Tenofovir Treatment Group 4	Drug: BMS-663068 Tablets, Oral, 1200 mg, once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Drug: Raltegravir Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Other Name: Isentress Drug: Tenofovir Tablets, Oral, 300 mg, Once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose Other Name: Viread
Active Comparator: Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir Treatment Group 1 (reference arm)	Drug: Raltegravir Tablets, Oral, 400 mg, twice daily (BID), 96 weeks Other Name: Isentress Drug: Tenofovir Tablets, Oral, 300 mg, Once daily (QD), 96 weeks Other Name: Viread Drug: Ritonavir Tablets, Oral, 100 mg, Once daily, 96 weeks Other Name: Norvir Drug: Atazanavir Capsules, Oral, 300 mg, Once daily, 96 weeks Other Name: Reyataz

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)

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01384734

Show 53 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators


Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS clinical trial educational resource This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01384734 History of Changes
Other Study ID Numbers:	AI438-011 2011-000437-36
Study First Received:	June 23, 2011
Last Updated:	August 23, 2016
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Mexico: Secretaria de Salud Mexico: Federal Commission for Protection Against Health Risks Peru: Instituto Nacional de Salud Germany: Federal Institute for Drugs and Medical Devices Romania: National Medicines Agency Spain: Spanish Agency of Medicines Russia: Ministry of Health of the Russian Federation South Africa: Medicines Control Council South Africa: National Health Research Ethics Council

Additional relevant MeSH terms:


Immunologic Deficiency Syndromes Acquired Immunodeficiency Syndrome HIV Infections Immune System Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Ritonavir Atazanavir Sulfate Tenofovir Raltegravir Potassium	HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors HIV Integrase Inhibitors Integrase Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016