Filibuvir In Treatment Naive Hepatitis C Virus (HCV) Genotype 1 Subjects (FITNESS)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Safety And Efficacy Of Filibuvir Plus Pegylated Interferon Alfa-2a And Ribavirin In Treatment-Naive, HCV Genotype 1 Infected Subjects

The primary objective for this study is to determine if the addition of filibuvir to a standard regimen of peginterferon/ribavirin (pegIFN/RBV) significantly increases the proportion of subjects who achieve a sustained viral response (SVR) compared to peginterferon/ribavirin (pegIFN/RBV) therapy alone.

Study Overview

• Status: Completed
• Conditions: Hepatitis; Hepatitis C
• Intervention / Treatment: Drug: Placebo; Drug: Filibuvir; Drug: Filibuvir

• Study Type: Interventional
• Enrollment (Actual): 288
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Pfizer Investigational Site
  • Bruxelles, Belgium, 1020
    • Pfizer Investigational Site
  • Edegem, Belgium, 2650
    • Pfizer Investigational Site
  • Gent, Belgium, 9000
    • Pfizer Investigational Site
  • Haine St. Paul, Belgium, 7100
    • Pfizer Investigational Site
  • Leuven, Belgium, 3000
    • Pfizer Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Pfizer Investigational Site
    • Edmonton, Alberta, Canada, T5H 4B9
      • Pfizer Investigational Site
    • Edmonton, Alberta, Canada, T5H 3V9
      • Pfizer Investigational Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Pfizer Investigational Site
    • Vancouver, British Columbia, Canada, V6Z2C7
      • Pfizer Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Pfizer Investigational Site
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Pfizer Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2L 4P9
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2X 2P4
      • Pfizer Investigational Site
• France
  • Clichy, France, 92110
    • Pfizer Investigational Site
  • Creteil cedex, France, 94010
    • Pfizer Investigational Site
  • Marseille cedex 8, France, 13285
    • Pfizer Investigational Site
  • Paris Cedex 12, France, 75571
    • Pfizer Investigational Site
  • Pessac Cedex, France, 33604
    • Pfizer Investigational Site
  • Rennes cedex 9, France, 35033
    • Pfizer Investigational Site
  • Vandoeuvre Les Nancy Cedex, France, 54511
    • Pfizer Investigational Site
• Germany
  • Berlin, Germany, 12157
    • Pfizer Investigational Site
  • Bonn, Germany, 53105
    • Pfizer Investigational Site
  • Duesseldorf, Germany, 40237
    • Pfizer Investigational Site
  • Hamburg, Germany, 20246
    • Pfizer Investigational Site
  • Hamburg, Germany, 20099
    • Pfizer Investigational Site
  • Kiel, Germany, 24146
    • Pfizer Investigational Site
  • Koeln, Germany, 50937
    • Pfizer Investigational Site
• Hungary
  • Bekescsaba, Hungary, 5600
    • Pfizer Investigational Site
  • Budapest, Hungary, 1126
    • Pfizer Investigational Site
  • Debrecen, Hungary, 4032
    • Pfizer Investigational Site
  • Gyula, Hungary, 5700
    • Pfizer Investigational Site
  • Kaposvar, Hungary, 7400
    • Pfizer Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 135-710
    • Pfizer Investigational Site
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00927
    • Pfizer Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • Pfizer Investigational Site
  • Barcelona, Spain, 08003
    • Pfizer Investigational Site
  • Cordoba, Spain, 14004
    • Pfizer Investigational Site
  • Madrid, Spain, 28034
    • Pfizer Investigational Site
  • Madrid, Spain, 28006
    • Pfizer Investigational Site
  • Madrid, Spain, 28029
    • Pfizer Investigational Site
  • Sevilla, Spain, 41014
    • Pfizer Investigational Site
  • Madrid
    • Majadahonda, Madrid, Spain, 28220
      • Pfizer Investigational Site
• United States
  • California
    • Anaheim, California, United States, 92801
      • Pfizer Investigational Site
    • Anaheim, California, United States, 92802
      • Pfizer Investigational Site
    • Coronado, California, United States, 92118
      • Pfizer Investigational Site
    • La Jolla, California, United States, 92037
      • Pfizer Investigational Site
    • Mather, California, United States, 95655
      • Pfizer Investigational Site
    • Sacramento, California, United States, 95817
      • Pfizer Investigational Site
    • Sacramento, California, United States, 95814
      • Pfizer Investigational Site
    • San Diego, California, United States, 92123
      • Pfizer Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Pfizer Investigational Site
    • Englewood, Colorado, United States, 80113
      • Pfizer Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • Pfizer Investigational Site
    • Jacksonville, Florida, United States, 32209
      • Pfizer Investigational Site
    • Jacksonville, Florida, United States, 32207
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32803
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32809
      • Pfizer Investigational Site
    • South Miami, Florida, United States, 33143
      • Pfizer Investigational Site
    • Winter Park, Florida, United States, 32789
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Pfizer Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Pfizer Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2622
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10021
      • Pfizer Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Pfizer Investigational Site
    • Durham, North Carolina, United States, 22713
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Pfizer Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Pfizer Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Pfizer Investigational Site
    • San Antonio, Texas, United States, 78234
      • Pfizer Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Pfizer Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female subjects at least 18 years of age.
• HCV seropositive.
• HCV RNA >10,000 IU/mL at screening.
• HCV Genotype 1. Subjects infected with a non-genotype 1 strain or mixed genotypes are not eligible.
• Treatment naïve (no prior treatment with IFN alfa +/ RBV regimens or investigational anti-HCV agents).
• Liver biopsy within two years (24 months) of Screening with non-cirrhotic fibrosis classification. For those subjects with liver biopsy outside of the time window or for those subjects with no history of liver biopsy, a biopsy must be performed prior to randomization.
• Ultrasound within 6 months of Screening for 1) those subjects with bridging fibrosis or 2) those subjects with AFP >50 and <100 ng/mL with no evidence of hepatocellular carcinoma. For those subjects with an ultrasound conducted outside the 6-month time window, an ultrasound must be performed prior to randomization.

Exclusion Criteria:

• Co-infection with either HIV or HBV.
• Evidence of severe or decompensated liver disease.
• Subjects with liver disease unrelated to HCV infection.
• Pre-existing medical condition that makes the subject unsuitable for treatment with pegIFN/RBV therapy per product labeling.
• Laboratory abnormality at Screening that makes the subject unsuitable for treatment with pegIFN/RBV therapy per product labeling.
• Abnormal ECG suggestive of clinically significant cardiac disease or QTc>450msec.
• History of organ transplant.
• Contraindicated medications being taken by the subject at the time of randomization that must be continued during the study period, including potent CYP3A4 inhibitors, sensitive CYP3A4 substrates, CYP3A4 substrates with narrow therapeutic range and CYP3A4 inducers.
• Active alcohol or substance abuse sufficient, in the Investigator's judgment, to prevent adherence to study medication and/or follow up.
• Pregnant or nursing females.
• Males whose female partner is pregnant.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Filibuvir 300 mg BID + pegIFN/RBV x 24 weeks (subjects with undetectable HCV RNA at week 4) - or - Filibuvir 300 mg BID + pegIFN/RBV x 24 weeks followed by pegIFN/RBV x 24 weeks (subjects with detectable HCV RNA at week 4)	Drug: Filibuvir; 300 mg BID; Drug: Filibuvir; 600 mg BID
Experimental: Arm B; Filibuvir 600 mg BID + pegIFN/RBV x 24 weeks (subjects with undetectable HCV RNA at week 4) - or - Filibuvir 600 mg BID + pegIFN/RBV x 24 weeks followed by pegIFN/RBV x 24 weeks (subjects with detectable HCV RNA at week 4)	Drug: Filibuvir; 300 mg BID; Drug: Filibuvir; 600 mg BID
Placebo Comparator: Arm C; Placebo + pegIFN/RBV x 24 weeks followed by pegIFN/RBV x 24 weeks	Drug: Placebo; BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Viral Response (SVR) at Week 72	For participants who received filibuvir, had undetectable HCV RNA from Week 4 through 24 and discontinued therapy at Week 24, SVR was defined as undetectable plasma HCV RNA levels (<15 IU/mL) at both Week 24 (End of Treatment [EOT]) and Week 72, regardless of the HCV RNA levels between Week 24 and 72. For participants who received filibuvir, had detectable HCV RNA at Week 4 or later and discontinued therapy at Week 48 or who received placebo, SVR was defined as undetectable plasma HCV RNA levels (<15 IU/mL) at both Week 48 (EOT) and Week 72, regardless of the HCV RNA levels between Week 48 and 72.	Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4, 12, 24 and 48	Percentage of participants with undetectable HCV RNA at Week 4 (rapid viral response [RVR]), Week 12 (early viral response [EVR]), Week 24 and Week 48 were summarized. Undetectable HCV RNA was defined as plasma HCV RNA levels <15 IU/mL.	Week 4, 12, 24, 48
Percentage of Participants With Sustained Viral Response at 12 Weeks Following Completion of Therapy (SVR12)	A participant was considered to have achieved SVR12 if the plasma HCV RNA levels were <15 IU/mL at both the end of treatment (Week 24 or 48, depending on the time of therapy discontinuation based on HCV RNA levels during therapy) and 12 weeks following the completion of therapy (Week 36 for participants who ended therapy at Week 24; Week 60 for participants who ended therapy at Week 48). Overall percentage of participants with SVR12 was summarized.	12 weeks after completion of therapy (Week 36 or 60)
Percentage of Participants With Sustained Viral Response at 24 Weeks Following Completion of Therapy (SVR24)	SVR24 was summarized only for those participants who received filibuvir, had undetectable HCV RNA from Week 4 through 24 and discontinued therapy at Week 24 and all participants who received placebo for 48 weeks. A participant was considered to have achieved SVR24 if the plasma HCV RNA levels were <15 IU/mL at both the end of treatment (Week 24 for filibuvir participants who ended therapy at Week 24 and Week 48 for participants who received placebo) and 24 weeks following the completion of therapy (Week 48 for filibuvir participants who ended therapy at Week 24; Week 72 for placebo participants who ended therapy at Week 48).	24 weeks after completion of therapy (Week 48 or 72)
Percentage of Participants With Breakthrough Viremia	A participant was considered to have breakthrough viremia if there was a >2 log10 increase from nadir in HCV RNA concentration while on treatment or HCV RNA that became undetectable with treatment but then became persistently detectable (2 or more consecutive viral RNA measurements >1000 IU/mL) again during treatment. Overall percentage of participants with breakthrough viremia was summarized.	Baseline up to Week 48
Percentage of Participants With Relapsed Response	A participant was considered to have relapsed response if the plasma HCV RNA levels were undetectable at end of treatment (Week 24 or 48, depending on the time of therapy discontinuation based on HCV RNA levels during therapy) but detectable (>=15 IU/mL) during the off-treatment follow-up period up to Week 72. Overall percentage of participants with relapsed response was summarized.	Week 24 or Week 48 up to Week 72
Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4, 12 and 24	Plasma HCV RNA levels were measured using the Roche COBAS TaqMan assay (limit of detection: 15 IU/mL). Baseline value calculated as the average of the screening and Day 1 pre-dose measurements.	Baseline, Week 4, 12, 24
Number of Adverse Events (AEs) by Severity (All Causality)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Adverse events were graded as mild (did not interfere with participant's usual function), moderate (interfered to some extent with participant's usual function) or severe (interfered significantly with participant's usual function). The most severe grade was used in case of multiple occurrences of the same event.	Baseline up to Week 72
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Relationship to Study Drug (Any Therapy)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 72 that were absent before treatment or that worsened relative to pretreatment state. All causality AEs included SAEs as well as non-serious AEs, without regard to relationship to the study drug, which occurred during the trial. Treatment-related were events considered related to study drug by the investigator. Number of participants with treatment related TEAEs and all causality TEAEs were summarized.	Baseline up to Week 72
Number of Participants Who Discontinued Study Due to Adverse Events (AEs)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Baseline up to Week 72
Number of Participants With Dose Reduction or Temporary Discontinuation Due to Adverse Events (AEs)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Baseline up to Week 72
Number of Participants With Laboratory Test Abnormalities by Severity	Number of participants with laboratory abnormalities by Division of Auto Immune Disease Syndrome (DAIDS) grade of 4; 3 or 4; 2, 3 or 4 was summarized. Abnormal laboratory values refers to a DAIDS grade greater than 0, where grade 1= mild, grade 2= moderate, grade 3= severe and grade 4 = potentially life-threatening.	Baseline up to Week 72
Plasma Concentration of Filibuvir, Pegylated Interferon and Ribavirin		Week 0 (pre-dose), Week 2, 4, 8, 12, 16, 20, 24, 48 (only for those participants who received treatment till Week 48) post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Rodriguez-Torres M, Yoshida EM, Marcellin P, Srinivasan S, Purohit VS, Wang C, Hammond JL. A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV. Ann Hepatol. 2014 Jul-Aug;13(4):364-75.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: September 29, 2009
• First Submitted That Met QC Criteria: September 29, 2009
• First Posted (Estimate): September 30, 2009

Study Record Updates

• Last Update Posted (Estimate): January 27, 2014
• Last Update Submitted That Met QC Criteria: December 10, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Hepatitis C Polymerase Inhibitor PF-00868554 Filibuvir
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: A8121014