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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00987337
First received: September 29, 2009
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Hepatitis
Hepatitis C
Drug: Filibuvir
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Viral Response (SVR) at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4, 12, 24 and 48 [ Time Frame: Week 4, 12, 24, 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Sustained Viral Response at 12 Weeks Following Completion of Therapy (SVR12) [ Time Frame: 12 weeks after completion of therapy (Week 36 or 60) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Sustained Viral Response at 24 Weeks Following Completion of Therapy (SVR24) [ Time Frame: 24 weeks after completion of therapy (Week 48 or 72) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With Breakthrough Viremia [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Relapsed Response [ Time Frame: Week 24 or Week 48 up to Week 72 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4, 12 and 24 [ Time Frame: Baseline, Week 4, 12, 24 ] [ Designated as safety issue: No ]
    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.

  • Number of Adverse Events (AEs) by Severity (All Causality) [ Time Frame: Baseline up to Week 72 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Relationship to Study Drug (Any Therapy) [ Time Frame: Baseline up to Week 72 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Discontinued Study Due to Adverse Events (AEs) [ Time Frame: Baseline up to Week 72 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Dose Reduction or Temporary Discontinuation Due to Adverse Events (AEs) [ Time Frame: Baseline up to Week 72 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Laboratory Test Abnormalities by Severity [ Time Frame: Baseline up to Week 72 ] [ Designated as safety issue: Yes ]
    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.

  • Plasma Concentration of Filibuvir, Pegylated Interferon and Ribavirin [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 288
Study Start Date: November 2009
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
600 mg BID
Placebo Comparator: Arm C
Placebo + pegIFN/RBV x 24 weeks followed by pegIFN/RBV x 24 weeks
Drug: Placebo
BID

  Eligibility

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

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.
  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: NCT00987337

  Show 77 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00987337     History of Changes
Other Study ID Numbers: A8121014
Study First Received: September 29, 2009
Results First Received: December 10, 2013
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Hepatitis C Polymerase Inhibitor PF-00868554 Filibuvir

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 30, 2014