Efficacy and Safety Study of Pegylated Interferon Lambda-1a With Ribavirin and Daclatasvir, to Treat naïve Subjects With Chronic HCV Genotypes 1, 2, 3, and 4 Who Are Co-infected With HIV (DIMENSION)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01866930
First received: May 29, 2013
Last updated: July 9, 2014
Last verified: November 2013
  Purpose

To evaluate Sustained Virologic Response at post treatment Week 12 (SVR12)following treatment with Lambda/RBV/DCV in chronic HCV GT-1, -2, -3 or -4 subjects co-infected with HIV-1


Condition Intervention Phase
Chronic Hepatitis C Infection
Biological: Pegylated Interferon Lambda-1a
Drug: Daclatasvir (DCV)
Drug: Ribasphere (RBV)
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 3 Open Label Study Evaluating the Efficacy and Safety of Pegylated Interferon Lambda-1a, in Combination With Ribavirin and Daclatasvir, for Treatment of Chronic HCV Infection With Treatment naïve Genotypes 1, 2, 3 or 4 in Subjects Co-infected With HIV

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Antiviral activity, as determined by the proportion of subjects with SVR12, defined as HCV RNA <LLOQ (25 IU/mL), target detected or target not detected, for each treatment arm [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]

    SVR=Sustained virologic response

    HCV=Hepatitis C virus

    RNA=Ribonucleic acid

    LLOQ=Lower Limit of Quantification



Secondary Outcome Measures:
  • Proportion of subjects with Rapid virologic response (RVR) and Extended Rapid Virologic Response (eRVR), where RVR is defined as <LLOQ target not detected at week 4 and eRVR defined as <LLOQ target not detected at Weeks 4 and 12 [ Time Frame: RVR at Week 4 and eRVR at Weeks 4 and 12 ] [ Designated as safety issue: No ]
  • Proportion of subjects in each group/duration who achieve HCV RNA <LLOQ target detected or not detected, at end of therapy (SVR24) [ Time Frame: 24 weeks post treatment (SVR24) ] [ Designated as safety issue: No ]
  • Proportion of subjects with treatment emergent cytopenic abnormalities (anemia as defined by Hb <10 g/dL, and/or neutropenia as defined by ANC <750 mm3 and/or thrombocytopenia as defined by platelets <50,000 mm3) during the treatment period [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 20, and 24 (and Weeks 28, 32, 36, 40, 44, and 48 for subjects requiring those visits) ] [ Designated as safety issue: Yes ]

    Hb=Hemoglobin

    ANC=Absolute Neutrophil Count


  • Proportion of subjects with the following on treatment IFN-associated symptoms: flu-like symptoms (as defined by pyrexia or chills or pain) and musculoskeletal symptoms (as defined by arthralgia or myalgia or back pain) [ Time Frame: Weeks 1, 2, 4, 6, 8, 12, 20, and 24 (and Weeks 28, 32, 36, 40, 44, and 48 for subjects requiring those visits) ] [ Designated as safety issue: Yes ]
    IFN=Interferon

  • Frequency of deaths, serious adverse events (SAEs), discontinuations due to Adverse Events (AEs), dose reductions, and severity Grade 3/4 laboratory abnormalities [ Time Frame: From Day 1 until the end of treatment 24 weeks or 48 weeks: Weeks 1, 2, 4, 6, 8, 12, 20, and 24 (and Weeks 28, 32, 36, 40, 44, and 48 for subjects requiring those visits) ] [ Designated as safety issue: Yes ]
  • Absolute and percent change from baseline in the CD4 cell count, lymphocyte cell count, and platelet count [ Time Frame: Weeks 4, 8, 12 and 24 (and Week 36 for subjects requiring visit) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 300
Study Start Date: July 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A: GT-2 or -3 HCV Treatment Naïve Subjects

Pegylated Interferon Lambda 180 µg solution, injection subcutaneously once weekly for 24 weeks

Ribasphere 200 mg tablets (800 mg per day: two 200 mg tablets in the morning and two 200 mg tablets in the evening) by mouth twice daily for 24 weeks

Daclatasvir 30 mg, 60 mg, or 90 mg tablets (depending on concomitant HIV regimen) once daily for 12 weeks

Biological: Pegylated Interferon Lambda-1a
Other Name: BMS-914143
Drug: Daclatasvir (DCV)
Other Name: BMS-790052
Drug: Ribasphere (RBV)
Experimental: Cohort B: GT-1 or -4 HCV Treatment Naïve Subjects

Pegylated Interferon Lambda 180 µg solution, injection subcutaneously once weekly for 24 or 48 weeks

Ribasphere 200 mg tablets, (1000 mg per day: two 200 mg tablets in the morning and three 200 mg tablets in the evening for subjects weighing <75 kg and 1200 mg per day: three 200 mg tablets in morning and three 200 mg tablets in evening for subjects weighing ≥75 kg) by mouth twice daily for 24 or 48 weeks

Daclatasvir 30 mg, 60 mg, or 90 mg tablets (depending on concomitant HIV regimen) once daily for 12 weeks

Biological: Pegylated Interferon Lambda-1a
Other Name: BMS-914143
Drug: Daclatasvir (DCV)
Other Name: BMS-790052
Drug: Ribasphere (RBV)

Detailed Description:

Study Classification: Safety/Efficacy and Pharmacokinetics/dynamics

GT=genotype

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HCV Genotype-1, -2, -3 or -4 treatment naïve;
  • HCV RNA ≥10,000 IU/mL at screening;
  • HIV-1 infection [(approximately 200 subjects receiving HAART, approximately 100 subjects not receiving highly active antiretroviral therapy (HAART)];
  • For subjects receiving HAART, HIV RNA must be below <40 copies/mL at screening and <200 copies/mL for at least 8 weeks prior to screening;
  • CD4 cell count at screening must be ≥100 cells/μL if receiving HAART or ≥350 cells/μL if not receiving HAART)
  • Seronegative for Hepatitis B Surface Antigen (HBsAg)
  • Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive. BMI=weight (kg)/[height (m)]2 at screening;
  • Subjects with compensated cirrhosis are permitted, but the number of subjects will be capped at approximately 30%. If a subject does not have cirrhosis, a liver biopsy within 3 years prior to enrollment is required to demonstrate the absence of cirrhosis. If cirrhosis is present, any prior liver biopsy is sufficient. Fibroscan® or FibroTest are acceptable if performed within 1 year prior to treatment in countries where liver biopsy is not required prior to treatment and where non-invasive imaging tests are approved for staging of liver disease
  • Subjects with mild to moderate hemophilia as defined as:

    1. Mild-factor level activity of 6-4% OR
    2. Moderate defined as factor level activity of 1-5%

Exclusion Criteria:

  • Any evidence of liver disease other than chronic HCV;
  • Subjects infected with human immunodeficiency virus (HIV-2);
  • Diagnosed or suspected hepatocellular carcinoma;
  • Decompensated liver disease;
  • Presence of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within 12 weeks prior to study entry (AIDS-defining opportunistic infections as defined by the CDC, (CDC, JAMA 1993 Feb 10;269(6):729-30)
  • Laboratory values: ANC <1.5 x 109 cells/L (<1.2 x 109 cells/L for Blacks), platelet count <90 x 109 cells/L, hemoglobin <11 g/dL for females, hemoglobin <12 g/dL for males;
  • Subjects (receiving HAART) who had first initiated anti-retroviral therapy within last 8 weeks prior to Day 1; however, if changes are required to a subject's HAART regimen to meet the requirements of the protocol, these changes are allowed at the screening visit. Subjects should wait a minimum of 1 month prior to Day 1 after a repeat of HIV viral load has been confirmed, <40 copies/mL
  • Subjects on Zidovudine (AZT), Didanosine (ddI), or Stavudine (d4T);
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Subjects with severe hemophilia (defined as <1% factor activity level)
  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: NCT01866930

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Show 54 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: NCT01866930     History of Changes
Other Study ID Numbers: AI452-032, 2012-003280-22
Study First Received: May 29, 2013
Last Updated: July 9, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Canada: Health Canada
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Mexico: Federal Commission for Sanitary Risks Protection
Belgium: Federal Agency for Medicinal Products and Health Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency
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
Italy: The Italian Medicines Agency
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
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
Romania: Ministry of Labour, Family and Social Protection
Romania: Ministry of Public Health
Romania: National Medicines Agency
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Russia: FSI Scientific Center of Expertise of Medical Application

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferons
Ribavirin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014