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Dose-finding Study of BMS-955176 to Treat HIV-1 Infected Treatment-naive Adults

20 augusti 2018 uppdaterad av: ViiV Healthcare

A Phase 2b Randomized, Active-Controlled, Double-Blind Trial to Investigate Safety, Efficacy, and Dose-response of BMS-955176, Given on a Backbone of Tenofovir/Emtricitabine, in Treatment-Naive HIV-1 Infected Adults

The purpose of this study is to find at least one dose of BMS-955176 that will be safe, effective and tolerable for HIV-1 infected treatment naive adults.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Faktisk)

210

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Argentina
      • Buenos Aires, Argentina, 1141
        • GSK Investigational Site
      • Buenos Aires, Argentina, 1202
        • GSK Investigational Site
      • Córdoba, Argentina, X5000JJS
        • GSK Investigational Site
    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1181ACH
        • GSK Investigational Site
    • Santa Fe
      • Rosario, Santa Fe, Argentina, 2000
        • GSK Investigational Site
  • Chile
      • Santiago, Chile, 8360159
        • GSK Investigational Site
      • Santiago, Chile, 7560994
        • GSK Investigational Site
    • Región Metro De Santiago
      • Santiago, Región Metro De Santiago, Chile
        • GSK Investigational Site
  • Frankrike
      • Le Kremlin-Bicêtre, Frankrike, 94276
        • GSK Investigational Site
      • Lyon cedex 04, Frankrike, 69317
        • GSK Investigational Site
      • Nantes, Frankrike, 44093
        • GSK Investigational Site
      • Nice, Frankrike, 06202
        • GSK Investigational Site
      • Paris, Frankrike, 75013
        • GSK Investigational Site
      • Paris, Frankrike, 75012
        • GSK Investigational Site
      • Paris Cedex 10, Frankrike, 75475
        • GSK Investigational Site
  • Förenta staterna
    • California
      • Beverly Hills, California, Förenta staterna, 90211
        • GSK Investigational Site
      • Los Angeles, California, Förenta staterna, 90036
        • GSK Investigational Site
    • Florida
      • DeLand, Florida, Förenta staterna, 32720
        • GSK Investigational Site
    • Georgia
      • Atlanta, Georgia, Förenta staterna, 30312
        • GSK Investigational Site
      • Decatur, Georgia, Förenta staterna, 30033
        • GSK Investigational Site
    • New Mexico
      • Santa Fe, New Mexico, Förenta staterna, 87505
        • GSK Investigational Site
    • Oklahoma
      • Tulsa, Oklahoma, Förenta staterna, 74135
        • GSK Investigational Site
    • Texas
      • Fort Worth, Texas, Förenta staterna, 76104
        • GSK Investigational Site
  • Italien
    • Lombardia
      • Bergamo, Lombardia, Italien, 24127
        • GSK Investigational Site
      • Milano, Lombardia, Italien, 20127
        • GSK Investigational Site
      • Milano, Lombardia, Italien, 20157
        • GSK Investigational Site
      • Monza, Lombardia, Italien, 20900
        • GSK Investigational Site
  • Kanada
      • Quebec, Kanada, G1V 4G2
        • GSK Investigational Site
    • Alberta
      • Edmonton, Alberta, Kanada, T6G 2G3
        • GSK Investigational Site
    • Manitoba
      • Winnipeg, Manitoba, Kanada, R3A 1R9
        • GSK Investigational Site
    • Ontario
      • Ottawa, Ontario, Kanada, K1H 8L6
        • GSK Investigational Site
    • Quebec
      • Montreal, Quebec, Kanada, H3A 1T1
        • GSK Investigational Site
      • Montreal, Quebec, Kanada, H2L 4P9
        • GSK Investigational Site
      • Montreal, Quebec, Kanada, H4A 3J1
        • GSK Investigational Site
      • Montreal, Quebec, Kanada, H2L 5B1
        • GSK Investigational Site
  • Mexiko
      • DF, Mexiko, 14000
        • GSK Investigational Site
      • Durango, Mexiko, 34000
        • GSK Investigational Site
      • Mexico City, Mexiko, CP 14080
        • GSK Investigational Site
    • Aguascalientes
      • Fracc. Las Americas, Aguascalientes, Mexiko, 20020
        • GSK Investigational Site
    • Guanajuato
      • León, Guanajuato, Mexiko, 37000
        • GSK Investigational Site
  • Polen
      • Bydgoszcz, Polen, 85-030
        • GSK Investigational Site
      • Szczecin, Polen, 71-252
        • GSK Investigational Site
      • Warszawa, Polen, 01-201
        • GSK Investigational Site
      • Wroclaw, Polen, 50-220
        • GSK Investigational Site
  • Spanien
      • Alcala de Henares, Spanien, 28805
        • GSK Investigational Site
      • Badalona, Spanien, 08916
        • GSK Investigational Site
      • Madrid, Spanien, 28040
        • GSK Investigational Site
      • Madrid, Spanien, 28034
        • GSK Investigational Site
      • Santiago de Compostela, Spanien, 15706
        • GSK Investigational Site
  • Storbritannien
      • London, Storbritannien, E1 1BB
        • GSK Investigational Site
      • London, Storbritannien, W2 1NY
        • GSK Investigational Site
      • London, Storbritannien, SW10 9NH
        • GSK Investigational Site
      • Tooting, London, Storbritannien, SW17 0QT
        • GSK Investigational Site
    • Midlothian
      • Edinburgh, Midlothian, Storbritannien, EH4 2XU
        • GSK Investigational Site
  • Sydafrika
    • Free State
      • Bloemfontein, Free State, Sydafrika, 9301
        • GSK Investigational Site
  • Tyskland
      • Berlin, Tyskland, 13353
        • GSK Investigational Site
      • Berlin, Tyskland, 12157
        • GSK Investigational Site
      • Dortmund, Tyskland, 44137
        • GSK Investigational Site
    • Bayern
      • Muenchen, Bayern, Tyskland, 80335
        • GSK Investigational Site
      • Muenchen, Bayern, Tyskland, 80336
        • GSK Investigational Site
    • Niedersachsen
      • Hannover, Niedersachsen, Tyskland, 30625
        • GSK Investigational Site
    • Nordrhein-Westfalen
      • Bonn, Nordrhein-Westfalen, Tyskland, 53127
        • GSK Investigational Site
      • Duesseldorf, Nordrhein-Westfalen, Tyskland, 40225
        • GSK Investigational Site
      • Essen, Nordrhein-Westfalen, Tyskland, 45122
        • GSK Investigational Site

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • Men and non-pregnant women, at least 18 years of age
  • Antiretroviral treatment-naïve; defined as no current or previous exposure to > 1 week of an antiretroviral drug
  • Plasma HIV-1 RNA ≥ 1000 copies/mL
  • CD4 T-cell count > 200 cells/mm3

Exclusion Criteria:

  • Resistance or partial resistance to any study drug determined by tests at Screening
  • Current or historical genotypic and/or phenotypic drug resistance testing showing certain resistance mutations to EFV, TDF, FTC, Protease Inhibitors
  • Chronic hepatitis B virus (HBV)/ hepatitis C virus (HCV)
  • Blood tests that indicate normal liver function
  • Hemoglobin < 8.0 g/dL, platelets < 50,000 cells/mm3

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Trippel

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Arm 1: BMS-955176 60 mg + TDF/FTC
BMS-955176 at 60 mg active dose per day + BMS-955176 placebo matching 120 mg + efavirenz (EFV) placebo matching 600 mg + tenofovir/emtricitabine (TDF/FTC) 300/200 mg per day, orally
Läkemedel: BMS-955176
HIV Mognadshämmare
Läkemedel: TDF/FTC
TDF/FTC
Experimentell: Arm 2: BMS-955176 120 mg + TDF/FTC
BMS-955176 placebo matching 60 mg + BMS-955176 at 120mg active dose per day + EFV placebo matching 600mg + TDF/FTC 300/200mg per day, orally
Läkemedel: BMS-955176
HIV Mognadshämmare
Läkemedel: TDF/FTC
TDF/FTC
Experimentell: Arm 3: BMS-955176 180 mg + TDF/FTC
BMS-955176 at 60mg active dose per day + BMS-955176 at 120mg active dose per day + EFV placebo matching 600mg + TDF/FTC at 300/200mg per day, orally
Läkemedel: BMS-955176
HIV Mognadshämmare
Läkemedel: TDF/FTC
TDF/FTC
Aktiv komparator: Arm 4: EFV + TDF/FTC
BMS-955176 placebo matching 60mg + BMS-955176 placebo matching 120mg + EFV at 600mg per day + TDF/FTC 300/200mg per day
Läkemedel: TDF/FTC
TDF/FTC
Läkemedel: EFV
EFV

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <40 Copies Per Milliliter (c/mL) at Week 24 Using Food and Drug Administration (FDA) Snapshot Algorithm
Tidsram: Week 24
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV 1 RNA <40 c/mL at Week 24 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window (18 to 30 weeks) to determine response. Analysis was performed on mITT Population, which comprised of randomized participants who received at least 1 dose of BMS-955176/GSK3532795 or EFV.
Week 24

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of Participants With Plasma HIV-1 RNA < 40 c/mL at Weeks 48 and 96 Using FDA Snapshot Algorithm
Tidsram: Weeks 48 and 96
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV 1 RNA <40 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response. The analysis was performed using mITT Population (observed), which consisted of participants in the mITT Population excluding participants who had no HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). The data was not collected for Week 96 analysis; as the study was terminated early. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Weeks 48 and 96
Number of Participants With Plasma HIV-1 RNA < 200 c/mL at Week 24 Using FDA Snapshot Algorithm
Tidsram: Week 24
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV-1 RNA <200 c/mL at Week 24 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response.
Week 24
Number of Participants With Plasma HIV-1 RNA < 200 c/mL at Weeks 48 and 96
Tidsram: Weeks 48 and 96
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV-1 RNA <200 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response. The analysis was performed using mITT Population (observed), which consisted of participants in the mITT Population excluding participants who had no HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). The data was not collected for Week 96 analysis; as the study was terminated early. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Weeks 48 and 96
Number of Participants With Newly Emergent Genotypic Resistance Using All On-treatment Isolates
Tidsram: Week 24
The emergence of genotypic resistance among samples selected for drug resistance testing were assessed by searching for all reverse transcriptase substitutions and protease inhibitor substitutions listed in the International Acquired Immunodeficiency Syndrome (AIDS) Society-United States of America (IAS-USA) list of HIV-1 drug resistance mutations. The outcome was originally designed to be assessed up to 96 weeks of treatment, but it was analyzed up to Week 24 as the study was terminated early. The emergence of genotypic resistance is presented for participants in the mITT Population who had Baseline and on-treatment genotypic resistance testing and who had successful sequencing.
Week 24
Number of Participants With Newly Emergent Phenotypic Resistance Using All On-treatment Isolates
Tidsram: Week 24
Phenotypic resistance to a drug is defined as a fold change (i.e., ratio of the 50% inhibitory concentration (IC50) of the clinical isolate to the IC50 of the reference strain) which is greater than the cut-off for reduced susceptibility. Emergent phenotypic resistance to BMS-955176/GSK3532795 was defined as a Baseline fold change IC50<= 3 and an on-treatment fold change IC50>3. The number of participants with newly emergent phenotypic resistance is presented for participants in the mITT Population who had Baseline and on-treatment phenotypic resistance testing. The outcome was originally designed to be assessed up to 96 weeks of treatment, but it was analyzed up to Week 24 as the study was terminated early.
Week 24
Change From Baseline in Logarithm to the Base 10 (log10) HIV-1 RNA Over Time
Tidsram: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Blood samples were collected for analysis of HIV-1 RNA. Values obtained at Day 1 were considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Change from Baseline in plasma HIV-1 RNA (log10) is summarized over time for the mITT Population using observed values, which excluded participants without HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Change From Baseline in Cluster of Differentiation (CD)4+ Thymus (T)-Cell Counts Over Time
Tidsram: Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
CD4+ T-cell counts was assessed using flow cytometry. Values obtained at Day 1 were considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Change from Baseline in CD4+T- cell counts is summarized over time for the mITT Population using observed values, which excluded participants without HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Change From Baseline in the Percentage of CD4+ T-cells Over Time
Tidsram: Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
CD4+ T-cell counts overall was assessed using flow cytometry. Values obtained at Day 1 were considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Change from Baseline in percentage of CD4+T- cell counts is summarized over time for the mITT Population using observed values, which excluded participants without HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation (AELD)
Tidsram: Up to Week 96
Any untoward medical occurrence that at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE. Number of participants with SAEs and AELDs is summarized.
Up to Week 96
Number of Participants With at Least One Centers for Disease Control (CDC) Class C Events
Tidsram: Up to Week 96
The occurrence of new AIDS defining events that is CDC class C events is presented.
Up to Week 96
Maximum Observed Plasma Concentration (Cmax), Observed Pre-dose Plasma Concentration (C0) and Observed Plasma Concentration at the End of a Dosing Interval (Ctau) of BMS-955176/GSK3532795
Tidsram: Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Serial blood samples were collected at indicated time points for intensive pharmacokinetic (PK) assessment. The PK assessments were performed on evaluable PK Population, a sub-population which included all treated participants who had adequate PK profiles.
Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Time of Maximum Observed Plasma Concentration (Tmax) of BMS-955176/GSK3532795
Tidsram: Pre-dose (morning) and 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Serial blood samples were collected at indicated time points for intensive PK assessment.
Pre-dose (morning) and 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Area Under the Concentration-time Curve in One Dosing Interval (AUC [Tau]) of BMS-955176/GSK3532795
Tidsram: Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Serial blood samples were collected at indicated time points for intensive PK assessment.
Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

ViiV Healthcare

Samarbetspartners

GlaxoSmithKline

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

12 maj 2015

Primärt slutförande (Faktisk)

26 maj 2016

Avslutad studie (Faktisk)

21 augusti 2017

Studieregistreringsdatum

Först inskickad

11 mars 2015

Först inskickad som uppfyllde QC-kriterierna

9 april 2015

Första postat (Uppskatta)

14 april 2015

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

19 september 2018

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

20 augusti 2018

Senast verifierad

1 augusti 2018

Mer information

Termer relaterade till denna studie

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • 205891
  • 2013-005487-26 (EudraCT-nummer)
  • AI468-038 (Annan identifierare: Bristol-Myers Squibb)

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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