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)

Bristol-Myers Squibb (BMS)

Status and phase: Terminated; Phase 3

Conditions: Chronic Hepatitis C Infection

Treatments: Drug: Ribasphere (RBV); Drug: Daclatasvir (DCV); Biological: Pegylated Interferon Lambda-1a

Study type: Interventional

Funder types: Industry

Identifiers

NCT01866930

2012-003280-22 (EudraCT Number)

AI452-032

Details and patient eligibility

About

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

Full description

Study Classification: Safety/Efficacy and Pharmacokinetics/dynamics

GT=genotype

Enrollment: 453 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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453 participants in 2 patient groups

Cohort A: GT-2 or -3 HCV Treatment Naïve Subjects

Experimental group

Description:

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

Treatment:

Biological: Pegylated Interferon Lambda-1a

Drug: Ribasphere (RBV)

Drug: Daclatasvir (DCV)

Cohort B: GT-1 or -4 HCV Treatment Naïve Subjects

Experimental group

Description:

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

Treatment:

Biological: Pegylated Interferon Lambda-1a

Drug: Ribasphere (RBV)

Drug: Daclatasvir (DCV)