Safety, Efficacy and Dose-response Study of BMS-986001 in Subjects With HIV-1 Infection Who Are Treatment-naive

A Phase IIb Randomized, Controlled, Partially Blinded Clinical Trial to Investigate Safety, Efficacy and Dose-response of BMS-986001 in Treatment-naive HIV-1-infected Subjects, Followed by an Open-label Period on the Recommended Dose

The purpose of this study is to identify at least one dose of BMS-986001 which is safe, well tolerated, and efficacious when combined with Efavirenz (EFV) + Lamivudine (3TC) for treatment-naive Human Immunodeficiency Virus 1 (HIV-1) infected subjects

Study Overview

• Status: Terminated
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: BMS-986001; Drug: BMS-986001; Drug: BMS-986001; Drug: Placebo matching with BMS-986001; Drug: Efavirenz; Drug: Lamivudine; Drug: Tenofovir

Detailed Description

Double Blind through Week 24. Partially Blind (to subjects, caregivers, Investigators) through Week 48.

• Study Type: Interventional
• Enrollment (Actual): 297
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad De Buenos Aires, Buenos Aires, Argentina, C1426EGR
      • Local Institution
• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Local Institution
    • Liverpool, New South Wales, Australia, 1871
      • Local Institution
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Local Institution
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z2C7
      • Local Institution
  • Quebec
    • Montreal, Quebec, Canada, H2L 4P9
      • Local Institution
    • Montreal, Quebec, Canada, H2L 5B1
      • Local Institution
• Chile
  • Santiago, Chile, 8207257
    • Local Institution
  • Santiago, Chile, 8330744
    • Local Institution
• Colombia
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • Local Institution
• France
  • Lyon, France, 69004
    • Local Institution
• Hungary
  • Budapest, Hungary, 1097
    • Local Institution
• Mexico
  • Distrito Federal
    • Mexico Df, Distrito Federal, Mexico, 06470
      • Local Institution
• Peru
  • Lima
    • Barranco, Lima, Peru, 4
      • Local Institution
    • Cercado, Lima, Peru, 1
      • Local Institution
    • San Martin De Porres, Lima, Peru, 31
      • Local Institution
  • Loreto
    • Iquitos, Loreto, Peru
      • Local Institution
• South Africa
  • Cape Town, South Africa, 7530
    • Local Institution
  • Durban, South Africa, 4001
    • Local Institution
  • Durban KZN, South Africa, 4001
    • Local Institution
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Local Institution
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2198
      • Local Institution
    • Soweto, Gauteng, South Africa, 2013
      • Local Institution
  • Kwa Zulu Natal
    • Dundee, Kwa Zulu Natal, South Africa, 3000
      • Local Institution
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Local Institution
• Spain
  • Badalona, Spain, 08916
    • Local Institution
  • Barcelona, Spain, 08036
    • Local Institution
  • Madrid, Spain, 28040
    • Local Institution
• Thailand
  • Bangkok, Thailand, 10400
    • Local Institution
  • Bangkok, Thailand, 10700
    • Local Institution
  • Bangkok, Thailand, 10330
    • Local Institution
  • Khon Kaen, Thailand, 40002
    • Local Institution
  • Nontaburi, Thailand, 11000
    • Local Institution
• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Florida
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • West Palm Beach, Florida, United States, 33401
      • Triple O Medical Services, P.A.
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Maryland
    • Washingtondc, Maryland, United States, 20009
      • Local Institution
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Clinic 42 And International Travel Clinic
  • New York
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • Buffalo, New York, United States, 14215
      • University at Buffalo
    • New York, New York, United States, 10011
      • Local Institution
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Local Institution
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Local Institution
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Bellaire, Texas, United States, 77401
      • St. Hope Foundation
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Disease Consultants
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, P.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• At least 18 years of age, (or minimum age as determined by local regulatory or as legal requirements dictate, whichever is higher)
• Plasma HIV-1 RNA > 5000 copies/mL
• Antiretroviral treatment-naive; defined as no current or previous exposure to > 1 week of an antiretroviral drug
• CD4+ T-cell count > 200 cells/mm3

Exclusion Criteria:

• Resistance to any of the study medications [Tenofovir Disoproxil Fumarate(TDF), Efavirenz (EFV), Lamivudine (3TC)] or to HIV Protease Inhibitors (PIs)
• Contraindications to any of the study drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: BMS-986001 (100 mg) + Placebo + Efavirenz + Lamivudine	Drug: BMS-986001; Capsules, Oral, 100 mg, Once daily, At least 48 weeks; Drug: BMS-986001; Capsules, Oral, 200 mg, Once daily, At least 48 weeks; Drug: BMS-986001; Capsules, Oral, 400 mg, Once daily, At least 48 weeks; Drug: Placebo matching with BMS-986001; Capsules, Oral, 0 mg, Once daily, At least 48 weeks; Drug: Efavirenz; Tablets, Oral, 600 mg, Once daily, Entire Treatment Phase; Other Names: Sustiva®; Drug: Lamivudine; Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase; Other Names: Epivir®
Experimental: Arm 2: BMS-986001 (200 mg) + Placebo + Efavirenz + Lamivudine	Drug: BMS-986001; Capsules, Oral, 100 mg, Once daily, At least 48 weeks; Drug: BMS-986001; Capsules, Oral, 200 mg, Once daily, At least 48 weeks; Drug: BMS-986001; Capsules, Oral, 400 mg, Once daily, At least 48 weeks; Drug: Placebo matching with BMS-986001; Capsules, Oral, 0 mg, Once daily, At least 48 weeks; Drug: Efavirenz; Tablets, Oral, 600 mg, Once daily, Entire Treatment Phase; Other Names: Sustiva®; Drug: Lamivudine; Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase; Other Names: Epivir®
Experimental: Arm 3: BMS-986001 (400 mg) + Efavirenz + Lamivudine	Drug: BMS-986001; Capsules, Oral, 100 mg, Once daily, At least 48 weeks; Drug: BMS-986001; Capsules, Oral, 200 mg, Once daily, At least 48 weeks; Drug: BMS-986001; Capsules, Oral, 400 mg, Once daily, At least 48 weeks; Drug: Efavirenz; Tablets, Oral, 600 mg, Once daily, Entire Treatment Phase; Other Names: Sustiva®; Drug: Lamivudine; Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase; Other Names: Epivir®
Experimental: Arm 4: Tenofovir (300 mg) + Efavirenz + Lamivudine	Drug: Efavirenz; Tablets, Oral, 600 mg, Once daily, Entire Treatment Phase; Other Names: Sustiva®; Drug: Lamivudine; Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase; Other Names: Epivir®; Drug: Tenofovir; Tablets, Oral, 300 mg, Once daily, Entire Treatment Phase; Other Names: Viread®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with plasma HIV-1 RNA < 50 c/mL as measured by polymerase chain reaction (PCR) analyses	Week 24
Safety as measured by numbers of subjects with Serious Adverse Events (SAEs) and numbers of subjects with Adverse Events (AEs) leading to discontinuations	Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with plasma HIV-1 RNA < 50 c/mL as measured by PCR analyses	Weeks 48 and 96
Safety as measured by numbers of subjects with SAEs and numbers of subjects with AEs leading to discontinuation	Weeks 48 and 96
Changes from baseline in CD4+ T-cell counts	Weeks 24, 48, and 96
Numbers of subjects with virologic failure who exhibit genotypic substitutions in viral Ribonucleic acid (RNA)	Weeks 24, 48, and 96
Maximum observed concentration (Cmax) of BMS-986001 when co-administered with EFV and 3TC	Week 24
Time of maximum observed concentration (Tmax) of BMS-986001 when co-administered with EFV and 3TC	Week 24
Trough plasma concentration at 24 h post observed dose (Cmin) of BMS-986001 when co-administered with EFV and 3TC	Week 24
Trough plasma concentration pre-dose (C0) of BMS-986001 when co-administered with EFV and 3TC	Week 24
Area under the concentration-time curve in one dosing interval [AUC(0-24)] of BMS-986001 when co-administered with EFV and 3TC	Week 24
Average steady-state plasma concentration (Css,avg) of BMS-986001 when co-administered with EFV and 3TC	Week 24

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Gupta SK, McComsey GA, Lombaard J, Echevarria J, Orrell C, Avihingsanon A, Osiyemi O, Santoscoy M, Ray N, Stock DA, Joshi SR, Hanna GJ, Lataillade M. Efficacy, safety, bone and metabolic effects of HIV nucleoside reverse transcriptase inhibitor BMS-986001 (AI467003): a phase 2b randomised, controlled, partly blinded trial. Lancet HIV. 2016 Jan;3(1):e13-22. doi: 10.1016/S2352-3018(15)00231-3. Epub 2015 Dec 12.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: December 7, 2011
• First Submitted That Met QC Criteria: December 8, 2011
• First Posted (Estimate): December 9, 2011

Study Record Updates

• Last Update Posted (Estimate): April 15, 2016
• Last Update Submitted That Met QC Criteria: March 17, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Lamivudine; Efavirenz
• Other Study ID Numbers: AI467-003; 2011-003329-89 (EudraCT Number)