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

20. august 2018 oppdatert 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.

Studieoversikt

Status

Avsluttet

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

210

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • 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
  • Canada
      • Quebec, Canada, G1V 4G2
        • GSK Investigational Site
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2G3
        • GSK Investigational Site
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A 1R9
        • GSK Investigational Site
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • GSK Investigational Site
    • Quebec
      • Montreal, Quebec, Canada, H3A 1T1
        • GSK Investigational Site
      • Montreal, Quebec, Canada, H2L 4P9
        • GSK Investigational Site
      • Montreal, Quebec, Canada, H4A 3J1
        • GSK Investigational Site
      • Montreal, Quebec, Canada, H2L 5B1
        • 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
  • Forente stater
    • California
      • Beverly Hills, California, Forente stater, 90211
        • GSK Investigational Site
      • Los Angeles, California, Forente stater, 90036
        • GSK Investigational Site
    • Florida
      • DeLand, Florida, Forente stater, 32720
        • GSK Investigational Site
    • Georgia
      • Atlanta, Georgia, Forente stater, 30312
        • GSK Investigational Site
      • Decatur, Georgia, Forente stater, 30033
        • GSK Investigational Site
    • New Mexico
      • Santa Fe, New Mexico, Forente stater, 87505
        • GSK Investigational Site
    • Oklahoma
      • Tulsa, Oklahoma, Forente stater, 74135
        • GSK Investigational Site
    • Texas
      • Fort Worth, Texas, Forente stater, 76104
        • 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
  • Italia
    • Lombardia
      • Bergamo, Lombardia, Italia, 24127
        • GSK Investigational Site
      • Milano, Lombardia, Italia, 20127
        • GSK Investigational Site
      • Milano, Lombardia, Italia, 20157
        • GSK Investigational Site
      • Monza, Lombardia, Italia, 20900
        • GSK Investigational Site
  • Mexico
      • DF, Mexico, 14000
        • GSK Investigational Site
      • Durango, Mexico, 34000
        • GSK Investigational Site
      • Mexico City, Mexico, CP 14080
        • GSK Investigational Site
    • Aguascalientes
      • Fracc. Las Americas, Aguascalientes, Mexico, 20020
        • GSK Investigational Site
    • Guanajuato
      • León, Guanajuato, Mexico, 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
  • Spania
      • Alcala de Henares, Spania, 28805
        • GSK Investigational Site
      • Badalona, Spania, 08916
        • GSK Investigational Site
      • Madrid, Spania, 28040
        • GSK Investigational Site
      • Madrid, Spania, 28034
        • GSK Investigational Site
      • Santiago de Compostela, Spania, 15706
        • GSK Investigational Site
  • Storbritannia
      • London, Storbritannia, E1 1BB
        • GSK Investigational Site
      • London, Storbritannia, W2 1NY
        • GSK Investigational Site
      • London, Storbritannia, SW10 9NH
        • GSK Investigational Site
      • Tooting, London, Storbritannia, SW17 0QT
        • GSK Investigational Site
    • Midlothian
      • Edinburgh, Midlothian, Storbritannia, EH4 2XU
        • GSK Investigational Site
  • Sør-Afrika
    • Free State
      • Bloemfontein, Free State, Sør-Afrika, 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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Trippel

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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
Legemiddel: BMS-955176
HIV-modningshemmer
Legemiddel: TDF/FTC
TDF/FTC
Eksperimentell: 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
Legemiddel: BMS-955176
HIV-modningshemmer
Legemiddel: TDF/FTC
TDF/FTC
Eksperimentell: 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
Legemiddel: BMS-955176
HIV-modningshemmer
Legemiddel: 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
Legemiddel: TDF/FTC
TDF/FTC
Legemiddel: EFV
EFV

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
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
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of Participants With Plasma HIV-1 RNA < 40 c/mL at Weeks 48 and 96 Using FDA Snapshot Algorithm
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

ViiV Healthcare

Samarbeidspartnere

GlaxoSmithKline

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

12. mai 2015

Primær fullføring (Faktiske)

26. mai 2016

Studiet fullført (Faktiske)

21. august 2017

Datoer for studieregistrering

Først innsendt

11. mars 2015

Først innsendt som oppfylte QC-kriteriene

9. april 2015

Først lagt ut (Anslag)

14. april 2015

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

19. september 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

20. august 2018

Sist bekreftet

1. august 2018

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Kliniske studier på Infeksjon, humant immunsviktvirus

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