Clinical trial NCT01718158: Efficacy and Safety Evaluation of a Regimen Consisting of Peginterferon Lambda-1a + Ribavirin + Daclatasvir (Lambda + RBV + DCV) in HCV Genotype 1b Treatment naïve Patients or Prior Relapsers to Peginterferon Alfa + Ribavirin (Alfa + RBV) Therapy
Official title: A Phase 3 Evaluation of Daclatasvir in Combination With Peginterferon Lambda-1a and Ribavirin (RBV) or Telaprevir in Combination With Peginterferon Alfa-2a and RBV in Patients With Chronic Hepatitis C Genotype 1b Who Are Treatment naïve or Prior Relapsers to Alfa/RBV Therapy (the STRUCTURE Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-10-31
Enrollment: 444
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 determine if treatment with Pegylated Interferon Lambda-1a, given in combination with Ribavirin and Daclatasvir for 24 weeks, is as safe and effective as the standard treatment with Pegylated Interferon Alfa-2a + Ribavirin + Telaprevir in subjects who are infected with Chronic Hepatitis C virus genotype 1b and have never received any prior anti-HCV treatment, or who have relapsed after an initial, successful treatment with Pegylated Interferon Alfa + Ribavirin


Eligibility criteria: Inclusion Criteria:

* Patients chronically infected with HCV Genotype-1b
* Naïve to prior treatment or documented evidence of relapse after completion of the prescribed duration of treatment (duration may be 24 or 48 weeks, to be determined based upon local guidelines)
* HCV RNA viral load ≥100,000 IU/mL at screening
* Patients with compensated cirrhosis are permitted

Exclusion Criteria:

* Infection with Hepatitis C virus (HCV) other than Genotype-1b
* Positive Hepatitis B surface antigen (HBsAg) or Human immunodeficiency virus (HIV)-1/HIV-2 antibody test at screening
* Evidence of chronic liver disease caused by diseases other than chronic HCV infection
* Current evidence of or history of variceal bleeding, hepatic encephalopathy, or ascites requiring diuretics or paracentesis or evidence of any of these findings on physical examination performed at screening
* Current or known history of cancer (except adequately treated in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin) within 5 years prior to screening
* Current evidence or known history of decompensated cirrhosis based on radiologic criteria or biopsy results and clinical criteria
* Laboratory values:

  1. Hemoglobin \<12.0 g/dL (males) or \<11.0 g/dL (females)
  2. Platelets \<90,000/mm3
  3. Total serum bilirubin ≥2 mg/dL (unless due to Gilbert's disease)

Primary outcomes:
measure: Proportion of subjects with Sustained Virologic Response at post-treatment follow-up Week 12 (SVR12)
timeFrame: Post treatment follow-up Week 12
Secondary outcomes:
measure: Proportion of subjects who achieve SVR12 in treatment-naive subjects
timeFrame: Post treatment follow-up Week 12
measure: Proportion of subjects with rash related dermatologic events
timeFrame: Up to 12 weeks of treatment
measure: Proportion of subjects who develop treatment emergent cytopenic abnormalities
timeFrame: Up to 48 Weeks
measure: Proportion of subjects with on-treatment interferon (IFN) associated flu like/musculoskeletal symptoms
timeFrame: Up to 48 Weeks
measure: Proportion of subjects who achieve SVR24 [Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Lower limit of quantitation (LLOQ)] at post-treatment follow-up Week 24
timeFrame: Post treatment follow-up Week 24
measure: Proportion of subjects with adverse events (AEs), Serious adverse events (SAEs), dose reductions, and discontinuations due to AEs through end of follow-up
timeFrame: Maximum of 72 weeks
measure: Proportion of subjects who achieve SVR12 with a 24-week treatment regimen
timeFrame: Post treatment follow-up Week 12
measure: Proportion of subjects who achieve Extended rapid virologic response (eRVR) (HCV RNA < LLOQ target not detected at Weeks 4 and 12 of treatment)
timeFrame: Weeks 4 and 12 of treatment
measure: Patient Health Questionnaire-9 (PHQ-9) score through end of follow-up
timeFrame: Maximum of 72 weeks
measure: Proportion of subjects with treatment emergent laboratory abnormalities by toxicity grade through End of treatment (EOT)
timeFrame: Maximum of 72 weeks
measure: Proportion of subjects with the following on-treatment interferon-associated neuropsychiatric symptoms through EOT
timeFrame: Maximum of 48 weeks
measure: Association of Single nucleotide polymorphism (SNPs) in Interleukin 28B (IL28B) (including rs12979860) or equilibrative nucleoside transporter 1 (ENT1) with clinical responses
timeFrame: Post-treatment follow-up Week 12
measure: Resistant variants associated with virologic failure through end of follow-up
timeFrame: Maximum of 72 weeks
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Va Long Beach Healthcare System
state: California
city: Marietta
country: United States
facility: Gastrointestinal Specialists Of Georgia Pc
state: Georgia
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group Of The Hudson Valley, Pc
state: New York
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Nashville
country: United States
facility: Nashville Medical Research Institute
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute, Llc
state: Texas
city: Houston
country: United States
facility: Medvamc
state: Texas
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Prov De Santa Fe
country: Argentina
facility: Local Institution
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Clichy Cedex
country: France
facility: Local Institution
city: Grenoble Cedex 9
country: France
facility: Local Institution
city: Villejuif Cedex
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Essen
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Mannheim
country: Germany
facility: Local Institution
city: Muenchen
country: Germany
facility: Local Institution
city: Haifa
country: Israel
facility: Local Institution
city: Tel Aviv
country: Israel
facility: Local Institution
city: Tel-Hashomer
country: Israel
facility: Local Institution
city: Zafed
country: Israel
facility: Local Institution
city: Foggia
country: Italy
facility: Local Institution
city: Messina
country: Italy
facility: Local Institution
city: Modena
country: Italy
facility: Local Institution
city: Pavia
country: Italy
facility: Local Institution
city: Pisa
country: Italy
facility: Local Institution
city: Nagoya-shi
country: Japan
facility: Local Institution
state: Aichi
city: Kitakyushu-shi
country: Japan
facility: Local Institution
state: Fukuoka
city: Kitakyushu
country: Japan
facility: Local Institution
state: Fukuoka
city: Hiroshima-shi
country: Japan
facility: Local Institution
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Local Institution
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Local Institution
state: Hyogo
city: Higashiibaraki-gun
country: Japan
facility: Local Institution
state: Ibaraki
city: Kawasaki-shi
country: Japan
facility: Local Institution
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Local Institution
state: Kanagawa
city: Yokohama
country: Japan
facility: Local Institution
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: Local Institution
state: Kyoto
city: Kyoto-shi
country: Japan
facility: Local Institution
state: Kyoto
city: Minato-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Musashino-shi
country: Japan
facility: Local Institution
state: Tokyo
city: Sumida-ku
country: Japan
facility: Local Institution
state: Tokyo
city: Tanabe-shi
country: Japan
facility: Local Institution
state: Wakayama
city: Gifu
country: Japan
facility: Local Institution
city: Kumamoto
country: Japan
facility: Local Institution
city: Saga
country: Japan
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Bialystok
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Myslowice
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Stavropol
country: Russian Federation
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Santander
country: Spain
facility: Local Institution
city: Zaragoza
country: Spain
facility: Local Institution
city: Kaohsiung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Tainan
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taoyuan
country: Taiwan
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Flisiak R, Kawazoe S, Znoyko O, Assy N, Gadano A, Kao JH, Lee KS, Zwirtes R, Portsmouth S, Dong Y, Xu D, Kumada H, Srinivasan S. Peginterferon Lambda-1a/Ribavirin with Daclatasvir or Peginterferon Alfa-2a/Ribavirin with Telaprevir for Chronic Hepatitis C Genotype 1b. J Interferon Cytokine Res. 2016 Nov;36(11):635-643. doi: 10.1089/jir.2015.0173. Epub 2016 Jun 21.