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 (STRUCTURE)

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)

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

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Ribavirin; Drug: Daclatasvir; Drug: Telaprevir; Biological: Peginterferon Lambda-1a; Biological: Peginterferon Alfa-2a

• Study Type: Interventional
• Enrollment (Actual): 444
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1119
    • Local Institution
  • Buenos Aires, Argentina, 1221
    • Local Institution
  • Buenos Aires, Argentina, C1181
    • Local Institution
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, C1405BCK
      • Local Institution
    • Mar Del Plata, Buenos Aires, Argentina, B7600FZN
      • Local Institution
  • Santa Fe
    • Prov De Santa Fe, Santa Fe, Argentina, 2000
      • Local Institution
• France
  • Clichy Cedex, France, 92118
    • Local Institution
  • Grenoble Cedex 9, France, 38043
    • Local Institution
  • Villejuif Cedex, France, 94804
    • Local Institution
• Germany
  • Berlin, Germany, 13353
    • Local Institution
  • Essen, Germany, 45122
    • Local Institution
  • Hamburg, Germany, 20099
    • Local Institution
  • Mannheim, Germany, 68167
    • Local Institution
  • Muenchen, Germany, 81377
    • Local Institution
• Israel
  • Haifa, Israel, 34362
    • Local Institution
  • Tel Aviv, Israel, 64239
    • Local Institution
  • Tel-Hashomer, Israel, 52621
    • Local Institution
  • Zafed, Israel, 13110
    • Local Institution
• Italy
  • Foggia, Italy, 71100
    • Local Institution
  • Messina, Italy, 98125
    • Local Institution
  • Modena, Italy, 41100
    • Local Institution
  • Pavia, Italy, 27100
    • Local Institution
  • Pisa, Italy, 56124
    • Local Institution
• Japan
  • Gifu, Japan, 5008727
    • Local Institution
  • Kumamoto, Japan, 8628655
    • Local Institution
  • Saga, Japan, 8408571
    • Local Institution
  • Aichi
    • Nagoya-shi, Aichi, Japan, 4678602
      • Local Institution
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 8030816
      • Local Institution
    • Kitakyushu-shi, Fukuoka, Japan, 8028533
      • Local Institution
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 7348511
      • Local Institution
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 0600033
      • Local Institution
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 6500047
      • Local Institution
  • Ibaraki
    • Higashiibaraki-gun, Ibaraki, Japan, 3313193
      • Local Institution
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 2138587
      • Local Institution
    • Yokohama, Kanagawa, Japan, 2320024
      • Local Institution
    • Yokohama-shi, Kanagawa, Japan, 2458575
      • Local Institution
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 6028566
      • Local Institution
    • Kyoto-shi, Kyoto, Japan, 6128555
      • Local Institution
  • Tokyo
    • Minato-ku, Tokyo, Japan, 1058470
      • Local Institution
    • Musashino-shi, Tokyo, Japan, 1808610
      • Local Institution
    • Sumida-ku, Tokyo, Japan, 1308575
      • Local Institution
  • Wakayama
    • Tanabe-shi, Wakayama, Japan, 6468558
      • Local Institution
• Korea, Republic of
  • Busan, Korea, Republic of, 614-735
    • Local Institution
  • Seoul, Korea, Republic of, 138-736
    • Local Institution
  • Seoul, Korea, Republic of, 135-720
    • Local Institution
  • Seoul, Korea, Republic of, 110-774
    • Local Institution
  • Seoul, Korea, Republic of, 143-729
    • Local Institution
• Poland
  • Bialystok, Poland, 15-540
    • Local Institution
  • Lodz, Poland, 91-347
    • Local Institution
  • Myslowice, Poland, 41-400
    • Local Institution
  • Wroclaw, Poland, 50-349
    • Local Institution
• Russian Federation
  • Moscow, Russian Federation, 119992
    • Local Institution
  • Moscow, Russian Federation, 125367
    • Local Institution
  • Moscow, Russian Federation, 111123
    • Local Institution
  • Moscow, Russian Federation, 119991
    • Local Institution
  • Moscow, Russian Federation, 121170
    • Local Institution
  • St. Petersburg, Russian Federation, 191167
    • Local Institution
  • St. Petersburg, Russian Federation, 196645
    • Local Institution
  • Stavropol, Russian Federation, 355017
    • Local Institution
• Spain
  • Barcelona, Spain, 08916
    • Local Institution
  • Madrid, Spain, 28029
    • Local Institution
  • Santander, Spain, 39008
    • Local Institution
  • Zaragoza, Spain, 50009
    • Local Institution
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Local Institution
  • Taichung, Taiwan, 404
    • Local Institution
  • Tainan, Taiwan, 704
    • Local Institution
  • Taipei, Taiwan, 100
    • Local Institution
  • Taipei, Taiwan, 112
    • Local Institution
  • Taoyuan, Taiwan, 333
    • Local Institution
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
      • Local Institution
• United States
  • California
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia PC
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • Poughkeepsie, New York, United States, 12601
      • Premier Medical Group of the Hudson Valley, PC
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102
      • Lehigh Valley Health Network
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Nashville Medical Research Institute
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute, LLC
    • Houston, Texas, United States, 77030
      • MEDVAMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Peginterferon Lambda-1a + Ribavirin + Daclatasvir; Peginterferon Lambda-1a 180 µg solution for subcutaneous injection, once a week for 24 Weeks Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 weeks Daclatasvir 60 mg tablets by mouth, once a day for 12 weeks	Drug: Ribavirin; Other Names: Copegus®; Drug: Daclatasvir; Other Names: BMS-790052; Biological: Peginterferon Lambda-1a; Other Names: BMS-914143
EXPERIMENTAL: Peginterferon Alfa-2a + Ribavirin + Telaprevir; Peginterferon Alfa-2a 180 µg solution for subcutaneous injection, once a week for 24 to 48 weeks depending on response Ribavirin 200 mg tablets [1000-1200 mg total daily dose: subjects should take either 400 mg (2 tablets for subjects < 75 kg) or 600 mg (3 tablets for subjects ≥ 75 kg) in the morning with food and 600 mg (3 tablets) in the evening with food] by mouth, twice daily, for 24 to 48 weeks depending on response Telaprevir 375 mg tablets [2250 mg total daily dose: subjects should take 750 mg (two 375 mg tablets) orally three times a day, approximately 7-9 hours apart) for 12 weeks	Drug: Ribavirin; Other Names: Copegus®; Drug: Telaprevir; Other Names: Incivek®; Biological: Peginterferon Alfa-2a; Other Names: Pegasys®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with Sustained Virologic Response at post-treatment follow-up Week 12 (SVR12)	Post treatment follow-up Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects who achieve SVR12 in treatment-naive subjects		Post treatment follow-up Week 12
Proportion of subjects with rash related dermatologic events		Up to 12 weeks of treatment
Proportion of subjects who develop treatment emergent cytopenic abnormalities	Treatment emergent cytopenic abnormalities [anemia as defined by Hemoglobin (Hb) < 10 g/dL, and/or neutropenia as defined by absolute neutrophil count (ANC) < 750/mm3, and or thrombocytopenia as defined by platelets < 50,000/mm3]	Up to 48 Weeks
Proportion of subjects with on-treatment interferon (IFN) associated flu like/musculoskeletal symptoms		Up to 48 Weeks
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	SVR24 = Sustained virologic response at post treatment follow-up Week 24	Post treatment follow-up Week 24
Proportion of subjects with adverse events (AEs), Serious adverse events (SAEs), dose reductions, and discontinuations due to AEs through end of follow-up		Maximum of 72 weeks
Proportion of subjects who achieve SVR12 with a 24-week treatment regimen		Post treatment follow-up Week 12
Proportion of subjects who achieve Extended rapid virologic response (eRVR) (HCV RNA < LLOQ target not detected at Weeks 4 and 12 of treatment)		Weeks 4 and 12 of treatment
Patient Health Questionnaire-9 (PHQ-9) score through end of follow-up		Maximum of 72 weeks
Proportion of subjects with treatment emergent laboratory abnormalities by toxicity grade through End of treatment (EOT)		Maximum of 72 weeks
Proportion of subjects with the following on-treatment interferon-associated neuropsychiatric symptoms through EOT	Psychiatric symptoms (depression, irritability or insomnia)	Maximum of 48 weeks
Association of Single nucleotide polymorphism (SNPs) in Interleukin 28B (IL28B) (including rs12979860) or equilibrative nucleoside transporter 1 (ENT1) with clinical responses	For each SNP in each candidate gene, allele and genotype frequencies will be summarized by treatment regimen	Post-treatment follow-up Week 12
Resistant variants associated with virologic failure through end of follow-up		Maximum of 72 weeks

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: October 29, 2012
• First Submitted That Met QC Criteria: October 29, 2012
• First Posted (ESTIMATE): October 31, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 9, 2015
• Last Update Submitted That Met QC Criteria: September 23, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: AI452-021; 2011-005409-65 (EUDRACT_NUMBER)