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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01718158
First received: October 29, 2012
Last updated: July 23, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Hepatitis C
Biological: Peginterferon Lambda-1a
Biological: Peginterferon Alfa-2a
Drug: Ribavirin
Drug: Daclatasvir
Drug: Telaprevir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Proportion of subjects with Sustained Virologic Response at post-treatment follow-up Week 12 (SVR12) [ Time Frame: Post treatment follow-up Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects who achieve SVR12 in treatment-naive subjects [ Time Frame: Post treatment follow-up Week 12 ] [ Designated as safety issue: No ]
  • Proportion of subjects with rash related dermatologic events [ Time Frame: Up to 12 weeks of treatment ] [ Designated as safety issue: Yes ]
  • Proportion of subjects who develop treatment emergent cytopenic abnormalities [ Time Frame: Up to 48 Weeks ] [ Designated as safety issue: Yes ]
    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]

  • Proportion of subjects with on-treatment interferon (IFN) associated flu like/musculoskeletal symptoms [ Time Frame: Up to 48 Weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Post treatment follow-up Week 24 ] [ Designated as safety issue: No ]
    SVR24 = Sustained virologic response at 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 [ Time Frame: Maximum of 72 weeks ] [ Designated as safety issue: Yes ]
  • Proportion of subjects who achieve SVR12 with a 24-week treatment regimen [ Time Frame: Post treatment follow-up Week 12 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve Extended rapid virologic response (eRVR) (HCV RNA < LLOQ target not detected at Weeks 4 and 12 of treatment) [ Time Frame: Weeks 4 and 12 of treatment ] [ Designated as safety issue: No ]
  • Patient Health Questionnaire-9 (PHQ-9) score through end of follow-up [ Time Frame: Maximum of 72 weeks ] [ Designated as safety issue: No ]
  • Proportion of subjects with treatment emergent laboratory abnormalities by toxicity grade through End of treatment (EOT) [ Time Frame: Maximum of 72 weeks ] [ Designated as safety issue: No ]
  • Proportion of subjects with the following on-treatment interferon-associated neuropsychiatric symptoms through EOT [ Time Frame: Maximum of 48 weeks ] [ Designated as safety issue: No ]
    Psychiatric symptoms (depression, irritability or insomnia)

  • Association of Single nucleotide polymorphism (SNPs) in Interleukin 28B (IL28B) (including rs12979860) or equilibrative nucleoside transporter 1 (ENT1) with clinical responses [ Time Frame: Post-treatment follow-up Week 12 ] [ Designated as safety issue: No ]
    For each SNP in each candidate gene, allele and genotype frequencies will be summarized by treatment regimen

  • Resistant variants associated with virologic failure through end of follow-up [ Time Frame: Maximum of 72 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 450
Study Start Date: January 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Biological: Peginterferon Lambda-1a
Other Name: BMS-914143
Drug: Ribavirin
Other Name: Copegus®
Drug: Daclatasvir
Other Name: BMS-790052
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

Biological: Peginterferon Alfa-2a
Other Name: Pegasys®
Drug: Ribavirin
Other Name: Copegus®
Drug: Telaprevir
Other Name: Incivek®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01718158

  Show 77 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01718158     History of Changes
Other Study ID Numbers: AI452-021, 2011‐005409‐65
Study First Received: October 29, 2012
Last Updated: July 23, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Germany: Ministry of Health
Israel: Israeli Health Ministry Pharmaceutical Administration
Israel: Ministry of Health
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Japan: Ministry of Health, Labor and Welfare
Korea: Food and Drug Administration
Poland: National Institute of Medicines
Poland: Ministry of Health
Poland: Ministry of Science and Higher Education
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: FSI Scientific Center of Expertise of Medical Application
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Taiwan: National Bureau of Controlled Drugs
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014