Safety, Tolerability, and Antiviral Activity of ANA598 Administered in Combination With Pegylated Interferon and Ribavirin for the Treatment of Genotype-1 Chronic HCV Infection

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple Dose Trial of the Safety, Efficacy, and Pharmacokinetics of ANA598 Administered With Pegylated Interferon and Ribavirin in Treatment-Naïve Genotype 1 Patients With Chronic Hepatitis C Infection

The purpose of this study is to assess the safety, tolerability and effectiveness of ANA598 when administered with pegylated interferon and ribavirin (Standard of Care [SOC]) compared to placebo + SOC.

Study Overview

• Status: Completed
• Conditions: HCV Infection
• Intervention / Treatment: Drug: placebo; Drug: Peginterferon; Drug: Ribavirin; Drug: ANA598; Drug: ANA598

Detailed Description

The safety, tolerability and antiviral activity of ANA598, administered orally at 200 mg BID or 400 mg BID for 12 weeks in combination with pegylated interferon and ribavirin (SOC) will be compared to placebo + SOC. Treatment-naïve patients with genotype 1 infection will be eligible for enrollment. Patients randomized to ANA598 will receive a loading dose of 800 mg q 12 hours administered on the first day of dosing. Patients with undetectable HCV RNA at week 4 and week 12 will be randomized to receive either an additional 12 or 36 weeks of SOC alone.

Ninety patients will be randomized into 2 cohorts. The forty-five patients in each cohort will be randomized as 30 active: 15 placebo.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Santurce, Puerto Rico, 00909
    • Puerto Rico
• United States
  • California
    • Anaheim, California, United States, 92801
      • United States, California 1
    • Los Angeles, California, United States, 90048
      • United States, California 4
    • San Clemente, California, United States, 92673
      • United States, California 2
    • San Diego, California, United States, 92120
      • United States, California 3
    • San Francisco, California, United States, 33136
      • United States, California 5
  • Florida
    • Gainesville, Florida, United States, 32601
      • United States, Florida 2
    • Miami, Florida, United States, 33136
      • United States, Florida 3
    • Sarasota, Florida, United States, 34209
      • United States, Florida 1
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • United States, Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • United States, Massachusetts
  • Michigan
    • Detroit, Michigan, United States, 48202
      • United States, Michigan
  • New York
    • New York, New York, United States, 10021
      • United States, New York
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • United States, North Carolina
    • Durham, North Carolina, United States, 27705
      • United States, North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • United States, Ohio
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • United States, Pennsylvania
  • Texas
    • Houston, Texas, United States, 77073
      • United States, Texas 2
    • San Antonio, Texas, United States, 78215
      • United States, Texas 1
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • United States, Virginia 1
    • Falls Church, Virginia, United States, 22042
      • United States, Virginia 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, ages 18 to 65 years
• Documented chronic HCV infection, genotype 1a or 1b
• Treatment-naïve

Exclusion Criteria:

• Female patients who are pregnant or breast-feeding
• Infection with non-genotype 1 HCV
• Previous treatment for HCV infection
• HIV or HBV positive
• Any medical contraindication to Peg-IFN or RBV therapy
• History of any other known cause of liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1; Peginterferon and ribavirin + placebo BID for 12 weeks, followed by Peg-IFN and RBV for an additional 12 or 36 weeks	Drug: placebo; oral BID; Drug: Peginterferon; 180 μg dose via subcutaneous injection weekly; Drug: Ribavirin; oral 1000 mg/day for patients who weighed < 75 kg and 1200 mg/day for patients who weighed ≥ 75 kg
Experimental: 2; ANA598 200 mg BID + Peginterferon and ribavirin for 12 weeks, followed by Peg-IFN and RBV for an additional 12 or 36 weeks	Drug: Peginterferon; 180 μg dose via subcutaneous injection weekly; Drug: Ribavirin; oral 1000 mg/day for patients who weighed < 75 kg and 1200 mg/day for patients who weighed ≥ 75 kg; Drug: ANA598; oral 200mg BID; Drug: ANA598; oral 400mg BID
Experimental: 3; ANA598 400mg BID + Peginterferon and ribavirin for 12 weeks, followed by Peg-IFN and RBV for an additional 12 or 36 weeks	Drug: Peginterferon; 180 μg dose via subcutaneous injection weekly; Drug: Ribavirin; oral 1000 mg/day for patients who weighed < 75 kg and 1200 mg/day for patients who weighed ≥ 75 kg; Drug: ANA598; oral 200mg BID; Drug: ANA598; oral 400mg BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Undetectable HCV RNA	12 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability	Throughout study
Undetectable HCV RNA	Week 4, Week 24, and Week 48
ANA598, Peg-IFN-a-2-a, ribavirin concentrations	Various time points through Week 12
Undetectable HCV RNA	24 weeks after completion of therapy for sustained virologic response [SVR]

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: September 16, 2009
• First Submitted That Met QC Criteria: September 16, 2009
• First Posted (Estimate): September 17, 2009

Study Record Updates

• Last Update Posted (Actual): March 31, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Infections; Communicable Diseases; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: ANA598-504