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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01384734
First received: June 23, 2011
Last updated: August 26, 2014
Last verified: August 2014
  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:


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: July 2018
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
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

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Show 56 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 26, 2014
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:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Ritonavir
Atazanavir
Tenofovir
Tenofovir disoproxil
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014