Clinical trial NCT01866930: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Hepatitis C Infection
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-06-03
Enrollment: 453
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: Study Classification: Safety/Efficacy and Pharmacokinetics/dynamics

GT=genotype

Eligibility 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)

Primary outcomes:
measure: Number of Participants With Sustained Virologic Response at Post-treatment Week 12 (SVR12)
timeFrame: Follow-up week 12
Secondary outcomes:
measure: Number of Participants With Rapid Virologic Response (RVR) and Extended Rapid Virologic Response (eRVR)
timeFrame: Treatment weeks 4 and 12
measure: Number of Subjects With Sustained Virologic Response at Post-treatment Week 24 (SVR24)
timeFrame: Follow-up week 24
measure: Number of Participants With Treatment Emergent Cytopenic Abnormalities
timeFrame: After Day 1 to end of treatment; up to Weeks 24 or 48
measure: Number of Participants With On-treatment IFN-associated Flu-like or Musculoskeletal Symptoms
timeFrame: After Day 1 to end of treatment; up to Weeks 24 or 48
measure: Number of Participants Who Died or Experienced Severe Adverse Events (SAEs), Dose Reductions of Lambda or Discontinuation Due to Adverse Events (AEs)
timeFrame: After Day 1 to end of treatment; up to Weeks 24 or 48
measure: Number of Participants With Treatment-emergent Grade 3/4 Lab Abnormalities
timeFrame: After Day 1 to end of treatment; up to Weeks 24 or 48
measure: Mean Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment
timeFrame: Day 1 to end of treatment; up to week 24 or week 48
measure: Mean Percent Change in Absolute CD4 T Lymphocyte Count From Baseline to End of Treatment
timeFrame: Day 1 to end of treatment; up to week 24 or week 48
measure: Mean Change in Total Lymphocyte Count From Baseline to End of Treatment
timeFrame: Day 1 to end of treatment; up to week 24 or week 48
measure: Mean Percent Change in Total Lymphocyte Count From Baseline to End of Treatment
timeFrame: Day 1 to end of treatment; up to week 24 or week 48
measure: Mean Change in Platelet Count From Baseline to End of Treatment
timeFrame: Day 1 to end of treatment; up to week 24 or week 48
measure: Mean Percent Change in Platelet Count From Baseline to End of Treatment
timeFrame: Day 1 to end of treatment; up to week 24 or week 48
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: San Francisco
country: United States
facility: University Of California San Francisco
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Aurora
country: United States
facility: University Of Colorado Denver & Hospital
state: Colorado
city: Aurora
country: United States
facility: University Of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Orlando
country: United States
facility: Orlando Va Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory Hospital Midtown Infectious Disease Clinic
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Durham
country: United States
facility: Duke Clinical Research Institute
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Health Network
state: Pennsylvania
city: Dallas
country: United States
facility: Ut Southwestern Medical Center
state: Texas
city: Buenos Aires, Bs As
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Antwerpen
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Edmonton
country: Canada
facility: University Of Alberta Hospitals
state: Alberta
city: Vancouver
country: Canada
facility: St Pauls Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver Id Reserach & Care Centre Society
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences, Mcmaster Site
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital General Campus
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: Mcgill University Health Centre (Muhc) Montreal Chest Institute
state: Quebec
city: Le Kremlin Bicetre
country: France
facility: Local Institution
city: Lyon
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Pessac Cedex
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Bonn
country: Germany
facility: Local Institution
city: Bonn
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Antella (fi)
country: Italy
facility: Local Institution
city: Brescia
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Monza
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Ciudad Juarez
country: Mexico
facility: Local Institution
state: Chihuahua
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Leon
country: Mexico
facility: Local Institution
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Lodz
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: Saint Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Volgograd
country: Russian Federation
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Cartagena (Murcia)
country: Spain
facility: Local Institution
city: Donosti-San Sebastian
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Brighton
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Nelson M, Rubio R, Lazzarin A, Romanova S, Luetkemeyer A, Conway B, Molina JM, Xu D, Srinivasan S, Portsmouth S. Safety and Efficacy of Pegylated Interferon Lambda, Ribavirin, and Daclatasvir in HCV and HIV-Coinfected Patients. J Interferon Cytokine Res. 2017 Mar;37(3):103-111. doi: 10.1089/jir.2016.0082. Epub 2017 Feb 17.