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

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ClinicalTrials.gov Identifier: NCT01384734

Recruitment Status : Completed

First Posted : June 29, 2011

Last Update Posted : June 1, 2018

Sponsor:

Information provided by (Responsible Party):

ViiV Healthcare

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Infection, Human Immunodeficiency Virus	Drug: BMS-663068 400 mg Drug: BMS-663068 800 mg Drug: BMS-663068 600 mg Drug: BMS-663068 1200 mg Drug: Raltegravir 400 mg Drug: Tenofovir 300 mg Drug: Ritonavir 100 mg Drug: Atazanavir 300 mg	Phase 2

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 Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	254 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, 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
Actual Study Start Date :	July 26, 2011
Actual Primary Completion Date :	February 18, 2013
Actual Study Completion Date :	May 12, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: BMS-663068 (400mg) + Raltegravir + Tenofovir Treatment Group 1	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: 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
Experimental: Arm B: BMS-663068 (800 mg) + Raltegravir + Tenofovir Treatment Group 2	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: 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
Experimental: Arm C: BMS-663068 (600 mg) + Raltegravir + Tenofovir Treatment Group 3	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: 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
Experimental: Arm D: BMS-663068 (1200 mg) + Raltegravir + Tenofovir Treatment Group 4	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
Active Comparator: Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir Treatment Group 1 (reference arm)	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

Outcome Measures

Primary Outcome Measures :

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 ]

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 ]
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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01384734

Show 56 Study Locations

Sponsors and Collaborators

ViiV Healthcare

Investigators


Study Director:	GSK Clinical Trials	ViiV Healthcare

More Information

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

Thompson M, Lalezari JP, Kaplan R, Pinedo Y, Pena OAS, Cahn P, Stock DA, Joshi SR, Hanna GJ, Lataillade M; AI438011 study team. Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in antiretroviral-experienced subjects: week 48 analysis of AI438011, a Phase IIb, randomized controlled trial. Antivir Ther. 2017;22(3):215-223. doi: 10.3851/IMP3112. Epub 2016 Dec 6.

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.


Responsible Party:	ViiV Healthcare
ClinicalTrials.gov Identifier:	NCT01384734 History of Changes
Other Study ID Numbers:	205889 AI438-011 ( Other Identifier: Bristol-Myers Squibb )
First Posted:	June 29, 2011 Key Record Dates
Last Update Posted:	June 1, 2018
Last Verified:	May 2018

Additional relevant MeSH terms:


Infection 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

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