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

NCT01384734 | Completed Phase 2 Results DMC

• 2 other identifiers: 205889AI438-011
• Study Type: interventional
• Target: 254
• Locations: 10 countries
• Sites: 54

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.

Conditions

Infection, Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) < 50 Copies Per Milliliter (c/mL) at Week 24

  Percentage of participants with plasma HIV 1 RNA \< 50 c/mL at Week 24 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to evaluate the antiviral activity. Treatment comparisons were not performed as this was an estimation study. Response rates were tabulated by treatment arm with exact Clopper-Pearson binomial 95 percentage confidence intervals (CI). Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the snapshot window of the visit of interest. Intent-To-Treat-Exposed (ITT-E) Population includes all randomized participants who received at least one dose of study treatment.

  Week 24

• Number of Participants With Serious Adverse Events (SAE) and Discontinuation Due to AEs up to Week 24

  Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or suspected transmission of an infectious agent via the study drug were categorized as SAE. AEs leading to discontinuation of study therapy were also reported as safety assessment. Safety population included all participants who received at least one dose of study treatment. Summaries of SAEs and AEs leading to discontinuation or withdrawal through Week 24 included AEs with onset on or after the start of study treatment (i.e. study date of first study treatment intake) up to and including the end of the Week 24 visit snapshot window.

  Up to Week 24

Secondary Outcomes (15)

• Change From Monotherapy Baseline in log10 HIV RNA of the Monotherapy Period

  Baseline and up to Day 8 of the monotherapy period

• Maximum Decrease From Monotherapy Baseline in log10 Plasma HIV-1 RNA

  Baseline and up to Day 8 of the monotherapy period

• Percentage of Participants With Plasma HIV-1 RNA < 50 c/mL at Day 8 of the Monotherapy Period

  Up to Day 8 of the monotherapy period

• Number of Participants With SAE and Discontinuation Due to AEs During Monotherapy Period

  Up to Day 8 of the monotherapy period

• Change From Monotherapy Baseline in Cluster of Differentiation (CD)4+ and CD8+ T-cell Counts During Monotherapy

  Baseline and Day 8

Study Arms (5)

Arm A: BMS-663068 (400mg) + Raltegravir + Tenofovir

EXPERIMENTAL

Treatment Group 1

Drug: BMS-663068 400 mg; Drug: Raltegravir 400 mg; Drug: Tenofovir 300 mg

Arm B: BMS-663068 (800 mg) + Raltegravir + Tenofovir

EXPERIMENTAL

Treatment Group 2

Drug: BMS-663068 800 mg; Drug: Raltegravir 400 mg; Drug: Tenofovir 300 mg

Arm C: BMS-663068 (600 mg) + Raltegravir + Tenofovir

EXPERIMENTAL

Treatment Group 3

Drug: BMS-663068 600 mg; Drug: Raltegravir 400 mg; Drug: Tenofovir 300 mg

Arm D: BMS-663068 (1200 mg) + Raltegravir + Tenofovir

EXPERIMENTAL

Treatment Group 4

Drug: BMS-663068 1200 mg; Drug: Raltegravir 400 mg; Drug: Tenofovir 300 mg

Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir

ACTIVE COMPARATOR

Treatment Group 1 (reference arm)

Drug: Raltegravir 400 mg; Drug: Tenofovir 300 mg; Drug: Ritonavir 100 mg; Drug: Atazanavir 300 mg

Interventions

BMS-663068 400 mg DRUG

Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose

Arm A: BMS-663068 (400mg) + Raltegravir + Tenofovir

BMS-663068 800 mg DRUG

Tablets, Oral, 800 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose

Arm B: BMS-663068 (800 mg) + Raltegravir + Tenofovir

BMS-663068 600 mg DRUG

Tablets, Oral, 600 mg, once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose

Arm C: BMS-663068 (600 mg) + Raltegravir + Tenofovir

BMS-663068 1200 mg DRUG

Tablets, Oral, 1200 mg, once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose

Arm D: BMS-663068 (1200 mg) + Raltegravir + Tenofovir

Raltegravir 400 mg DRUG

Tablets, Oral, 400 mg, twice daily (BID), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose

Arm A: BMS-663068 (400mg) + Raltegravir + Tenofovir; Arm B: BMS-663068 (800 mg) + Raltegravir + Tenofovir; Arm C: BMS-663068 (600 mg) + Raltegravir + Tenofovir; Arm D: BMS-663068 (1200 mg) + Raltegravir + Tenofovir; Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir

Tenofovir 300 mg DRUG

Tablets, Oral, 300 mg, Once daily (QD), 24+ weeks until optimal dose is selected, or 96 weeks if optimal dose

Arm A: BMS-663068 (400mg) + Raltegravir + Tenofovir; Arm B: BMS-663068 (800 mg) + Raltegravir + Tenofovir; Arm C: BMS-663068 (600 mg) + Raltegravir + Tenofovir; Arm D: BMS-663068 (1200 mg) + Raltegravir + Tenofovir; Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir

Ritonavir 100 mg DRUG

Tablets, Oral, 100 mg, Once daily, 96 weeks

Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir

Atazanavir 300 mg DRUG

Capsules, Oral, 300 mg, Once daily, 96 weeks

Arm E: Atazanavir + Ritonavir + Raltegravir + Tenofovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (54)

GSK Investigational Site

San Francisco, California, 94102, United States

Location

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20009, United States

Location

GSK Investigational Site

Coral Gables, Florida, 33134, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30312, United States

Location

GSK Investigational Site

New York, New York, 10008, United States

Location

GSK Investigational Site

Durham, North Carolina, 27710, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45267-0405, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Longview, Texas, 75605, United States

Location

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, C1202ABB, Argentina

Location

GSK Investigational Site

Rosario, Santa Fe Province, 2000, Argentina

Location

GSK Investigational Site

Buenos Aires, C1141ACG, Argentina

Location

GSK Investigational Site

Buenos Aires, C1426EGR, Argentina

Location

GSK Investigational Site

Córdoba, X5000JJS, Argentina

Location

GSK Investigational Site

Rosario, S2000CXP, Argentina

Location

GSK Investigational Site

Bogotá, Colombia

Location

GSK Investigational Site

Bonn, North Rhine-Westphalia, 53127, Germany

Location

GSK Investigational Site

Berlin, 12157, Germany

Location

GSK Investigational Site

Hamburg, 20099, Germany

Location

GSK Investigational Site

München, 80336, Germany

Location

GSK Investigational Site

Guadalajara, Jalisco, 44280, Mexico

Location

GSK Investigational Site

Zapopan, Jalisco, 45170, Mexico

Location

GSK Investigational Site

San Luis Potosí City, San Luis Potosí, 78240, Mexico

Location

GSK Investigational Site

Aguascalientes, 20230, Mexico

Location

GSK Investigational Site

DF, 14000, Mexico

Location

GSK Investigational Site

Distrito Federal, 03720, Mexico

Location

GSK Investigational Site

Mexico City, 3100, Mexico

Location

GSK Investigational Site

Iquitos, Loreto, Iqui 01, Peru

Location

GSK Investigational Site

Lima, 13, Peru

Location

GSK Investigational Site

Lima, 1, Peru

Location

GSK Investigational Site

Lima, 32, Peru

Location

GSK Investigational Site

Lima, 4, Peru

Location

GSK Investigational Site

Lima, Lima 11, Peru

Location

GSK Investigational Site

Lima, Lima 31, Peru

Location

GSK Investigational Site

Bucharest, 021105, Romania

Location

GSK Investigational Site

Constanța, 900709, Romania

Location

GSK Investigational Site

Craiova, Romania

Location

GSK Investigational Site

Iași, 700116, Romania

Location

GSK Investigational Site

Saint Petersburg, 190103, Russia

Location

GSK Investigational Site

Saint Petersburg, 191167, Russia

Location

GSK Investigational Site

Saint Petersburg, 196645, Russia

Location

GSK Investigational Site

Smolensk, 214006, Russia

Location

GSK Investigational Site

Dundee, KwaZulu-Natal, 3000, South Africa

Location

GSK Investigational Site

Durban, 4001, South Africa

Location

GSK Investigational Site

Johannesburg, 2010, South Africa

Location

GSK Investigational Site

Observatory, Cape Town, 7925, South Africa

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Córdoba, 14004, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

Related Publications (4)

• 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.

  PMID: 27922453 DERIVED

• 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.

  PMID: 26902761 DERIVED

• 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.

  PMID: 26423650 DERIVED

• 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.

  PMID: 24128669 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

fostemsavir; Raltegravir Potassium; Tenofovir; Ritonavir; Atazanavir Sulfate

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Sulfur Compounds; Azoles; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: June 29, 2011
• Study Start: July 26, 2011
• Primary Completion: February 18, 2013
• Study Completion: May 12, 2017
• Last Updated: November 14, 2018
• Results First Posted: November 14, 2018

Record last verified: 2018-08

Locations

DE (4); CO (1); RO (4); ZA (4); ME (7); US (13); PE (7); ES (4); AR (6); RU (4)