Clinical trial NCT01384734: HIV Attachment Inhibitor to Treat Human Immunodeficiency Virus 1 (HIV-1) Infections
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infection, Human Immunodeficiency Virus
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2011-06-29
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) < 50 Copies Per Milliliter (c/mL) at Week 24
timeFrame: Week 24
measure: Number of Participants With Serious Adverse Events (SAE) and Discontinuation Due to AEs up to Week 24
timeFrame: Up to Week 24
Secondary outcomes:
measure: Change From Monotherapy Baseline in log10 HIV RNA of the Monotherapy Period
timeFrame: Baseline and up to Day 8 of the monotherapy period
measure: Maximum Decrease From Monotherapy Baseline in log10 Plasma HIV-1 RNA
timeFrame: Baseline and up to Day 8 of the monotherapy period
measure: Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Day 8 of the Monotherapy Period
timeFrame: Up to Day 8 of the monotherapy period
measure: Number of Participants With SAE and Discontinuation Due to AEs During Monotherapy Period
timeFrame: Up to Day 8 of the monotherapy period
measure: Change From Monotherapy Baseline in Cluster of Differentiation (CD)4+ and CD8+ T-cell Counts During Monotherapy
timeFrame: Baseline and Day 8
measure: Change From Monotherapy Baseline in CD4+ and CD8+ T-cell Proportion During Monotherapy
timeFrame: Baseline and Day 8
measure: Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Primary Study
timeFrame: Weeks 48 and 96
measure: Number of Participants With SAE and Discontinuation Due to AEs During Primary Study
timeFrame: Weeks 48 and 96
measure: Change From Baseline in CD4+ T-cell Count
timeFrame: Baseline and Weeks 24, 48 and 96
measure: Number of Participants With Newly-emergent Genotypic Substitutions at Week 24
timeFrame: Up to Week 24
measure: Number of Participants With Newly-emergent Genotypic Substitutions at Week 48
timeFrame: Up to Week 48
measure: Number of Participants With Newly-emergent Genotypic Substitutions at Week 96
timeFrame: Up to Week 96
measure: Maximum Change From Baseline in Inhibitory Concentration at 50% (IC50) Fold Change Among Participants With VF at Week 24
timeFrame: Baseline and up to Week 24
measure: Change From Baseline in IC50 Fold Change Among Participants With VF at Week 48
timeFrame: Baseline and up to Week 48
measure: Change From Baseline in IC50 Fold Change Among Participants With VF at Week 96
timeFrame: Baseline and up to Week 96
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Coral Gables
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Longview
country: United States
facility: GSK Investigational Site
state: Texas
city: Ciudad de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Córdoba
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Bogota
country: Colombia
facility: GSK Investigational Site
city: Bogoto
country: Colombia
facility: GSK Investigational Site
city: Bogotá
country: Colombia
facility: GSK Investigational Site
city: Bonn
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: München
country: Germany
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Zapopan
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: San Luis Potosi
country: Mexico
facility: GSK Investigational Site
state: San Luis Potosí
city: Aguascalientes
country: Mexico
facility: GSK Investigational Site
city: DF
country: Mexico
facility: GSK Investigational Site
city: Distrito Federal
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Iquitos
country: Peru
facility: GSK Investigational Site
state: Loreto
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Smolensk
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Dundee
country: South Africa
facility: GSK Investigational Site
state: KwaZulu- Natal
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Johannesburg
country: South Africa
facility: GSK Investigational Site
city: Observatory, Cape Town
country: South Africa
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Córdoba
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: Lalezari JP, Latiff GH, Brinson C, Echevarria J, Trevino-Perez 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.
citation: 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.