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

Hepatitis C Clinical Trial

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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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00987337
• Other study ID #: A8121014
• Status: Completed
• Phase: Phase 2
• First received: September 29, 2009
• Last updated: December 10, 2013
• Start date: November 2009
• Est. completion date: January 2012

Study information

• Verified date: December 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 288
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• Filibuvir
300 mg BID
• Filibuvir
600 mg BID
• Placebo
BID

Locations

Country	Name	City	State
Belgium	Pfizer Investigational Site	Bruxelles
Belgium	Pfizer Investigational Site	Bruxelles
Belgium	Pfizer Investigational Site	Edegem
Belgium	Pfizer Investigational Site	Gent
Belgium	Pfizer Investigational Site	Haine St. Paul
Belgium	Pfizer Investigational Site	Leuven
Canada	Pfizer Investigational Site	Edmonton	Alberta
Canada	Pfizer Investigational Site	Edmonton	Alberta
Canada	Pfizer Investigational Site	Edmonton	Alberta
Canada	Pfizer Investigational Site	Halifax	Nova Scotia
Canada	Pfizer Investigational Site	Halifax	Nova Scotia
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Vancouver	British Columbia
Canada	Pfizer Investigational Site	Vancouver	British Columbia
France	Pfizer Investigational Site	Clichy
France	Pfizer Investigational Site	Creteil cedex
France	Pfizer Investigational Site	Marseille cedex 8
France	Pfizer Investigational Site	Paris Cedex 12
France	Pfizer Investigational Site	Pessac Cedex
France	Pfizer Investigational Site	Rennes cedex 9
France	Pfizer Investigational Site	Vandoeuvre Les Nancy Cedex
Germany	Pfizer Investigational Site	Berlin
Germany	Pfizer Investigational Site	Bonn
Germany	Pfizer Investigational Site	Duesseldorf
Germany	Pfizer Investigational Site	Hamburg
Germany	Pfizer Investigational Site	Hamburg
Germany	Pfizer Investigational Site	Kiel
Germany	Pfizer Investigational Site	Koeln
Hungary	Pfizer Investigational Site	Bekescsaba
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Debrecen
Hungary	Pfizer Investigational Site	Gyula
Hungary	Pfizer Investigational Site	Kaposvar
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Korea, Republic of	Pfizer Investigational Site	Seoul
Puerto Rico	Pfizer Investigational Site	Rio Piedras
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Barcelona
Spain	Pfizer Investigational Site	Cordoba
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Majadahonda	Madrid
Spain	Pfizer Investigational Site	Sevilla
United States	Pfizer Investigational Site	Anaheim	California
United States	Pfizer Investigational Site	Anaheim	California
United States	Pfizer Investigational Site	Aurora	Colorado
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Chicago	Illinois
United States	Pfizer Investigational Site	Coronado	California
United States	Pfizer Investigational Site	DeLand	Florida
United States	Pfizer Investigational Site	Durham	North Carolina
United States	Pfizer Investigational Site	Durham	North Carolina
United States	Pfizer Investigational Site	Englewood	Colorado
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Indianapolis	Indiana
United States	Pfizer Investigational Site	Jacksonville	Florida
United States	Pfizer Investigational Site	Jacksonville	Florida
United States	Pfizer Investigational Site	La Jolla	California
United States	Pfizer Investigational Site	Mather	California
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	New Orleans	Louisiana
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	Orlando	Florida
United States	Pfizer Investigational Site	Orlando	Florida
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Richmond	Virginia
United States	Pfizer Investigational Site	Sacramento	California
United States	Pfizer Investigational Site	Sacramento	California
United States	Pfizer Investigational Site	Salt Lake City	Utah
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	South Miami	Florida
United States	Pfizer Investigational Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Hungary,  Korea, Republic of,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No

External Links

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