Filibuvir in Treatment Naïve HCV Genotype 1 Subjects

• Register: EUCTR
• Last refreshed on: 21 January 2013
• Main ID: EUCTR2009-009214-40-DE
• Date of registration: 11/12/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017, USA
• Public title: Filibuvir in Treatment Naïve HCV Genotype 1 Subjects
• Scientific 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 NAÏVE, HCV GENOTYPE 1 INFECTED SUBJECTS - FITNESS
• Date of first enrolment: 26/02/2010
• Target sample size: 288
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-009214-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

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

Contacts

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
for enrollment into the study:
1. Male or female subjects at least 18 years of age.
2.A negative pregnancy test at Screening and immediately prior to start
of study medication for Women of Child Bearing Potential (WOCBP).
NOTE: WOCBP includes any female who has experienced menarche and
who has not undergone hysterectomy, bilateral oophorectomy or tubal
ligation or is not post-menopausal (aged >45, amennorheic for >2
years, and serum FSH levels >30 IU/L). Even women who are using
mechanical products (intrauterine devices; barrier methods) to prevent
pregnancy, who are practicing abstinence, or who have a partner that is
sterile (eg, vasectomy), should be considered to be of child bearing
potential.
3. Willingness to utilize effective barrier contraception for WOCBP, males
and their
partners, throughout the duration of the study and for at least 7 months
following the last dose of study medication. In addition, WOCBP must
use another acceptable method of contraception from screening to at
least 6 months after the trial. Acceptable contraception includes highly
effective intrauterine devices or
vasectomised partner. NOTE: oral, transdermal, implantable, or
injectable hormone therapy is NOT allowed.
4. HCV seropositive.
5. HCV RNA =10,000 IU/mL at screening.
6. HCV Genotype 1. Subjects infected with a non-genotype 1 strain or
mixed genotypes are not eligible.
7. Treatment naïve (no prior treatment with IFN-alpha+/- RBV regimens
or investigational anti-HCV agents).
8. Liver biopsy within two years (24 months) of Screening with noncirrhotic
fibrosis classification (Ishak score =4 or equivalent). A copy of
the pathology report must be available at the study site prior to
randomization. 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.
9. Ultrasound within 6 months of Screening for 1) those subjects with
bridging fibrosis or 2) those subjects with alpha-fetoprotein (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.
10. Evidence of a personally signed and dated informed consent
document indicating that the subject (or a legally acceptable
representative) has been informed of all pertinent aspects of the study.
11. Subjects who are willing and able to comply with scheduled visits,
treatment plan, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 277
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

Exclusion criteria:
Subjects presenting with any of the following will not be included in the
trial:
1. Co-infection with either HIV or HBV.
2. Infection with a non-genotype 1 strain of HCV or mixed genotypes.
3. Evidence of severe or decompensated liver disease, as evidenced but
not limited to by any of the following at Screening:
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a. Child-Pugh score >6;
b. Total serum bilirubin >2.5X ULN and direct bilirubin >1.5X ULN;
c. Serum albumin <2.0 g/dL;
d. Prothrombin time >1.5X ULN or INR >2.0X ULN;
e. AST or ALT >10X ULN;
f. History of ascites, bleeding varices, hepatic encephalopathy or
hepatocellular carcinoma.
4. Subjects with liver disease unrelated to HCV infection including but
not limited to:
a. Hemochromatosis;
b. Genetic liver disease:
1. Alpha-1 antitrypsin deficiency;
2. Wilson's disease.
c. Auto-immune disease;
1. Auto-immune hepatitis;
2. Auto-immune cholestatic disease.
d. Drug induced liver disease (history of ingestion of drugs known to
produce hepatic steatosis including corticosteroids, high-dose estrogens,
methotrexate, tetracycline or amiodarone in the previous 6 months;
e. Cholestatic liver disease; bile duct obstruction;
f. Alpha-fetoprotein (AFP) levels greater than 100 ng/ml;
g. Malignant neoplastic disease;
5. Pre-existing medical condition that makes the subject unsuitable for
treatment with pegIFN alpha/RBV therapy per product labeling
including, but not limited to:
a. Ocular abnormalities such as retinopathy, cotton wool spots, optic
nerve
disorders, retinal hemorrhage; etc.
b. Major psychiatric disorders (severe depression, schizophrenia,
psychosis, or a history of a suicide attempt).
6. Laboratory abnormality at Screening that makes the subject
unsuitable for treatment
with pegIFN alpha/RBV therapy per product labeling including, but not
limited to:
a. HbA1c >8.5%;
b. Estimated creatinine clearance of <50 mL/min;
c. Thyroid-stimulating hormone >1.2 x ULN or <0.8 x LLN (euthyroid
subjects exempt if euthyroid function is confirmed by T4/T3 testing);
d. ANA >1:640;
e. Hematologic abnormalities: hemoglobin <12 g/dL (women) or <13
g/dL (men),
platelet count <120,000 cells/mm3, and/or neutrophil count <1,500
cells/mm3;
7. Abnormal ECG suggestive of clinically significant cardiac disease or
QTc >450 msec at screening.
8. History of solid organ transplant.
9. 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.
10. Have the following reproductive hormones outside the specified
normal limits (males only):
Total Reference
Range(Conventional) Reference Range (SI)
Testosterone 1.75-7.81 ng/mL 6.07-27.10
nmol/L
LH 2.0-12.0 mIU/mL 2.0-12.0 IU/L
FSH 1.13-12.51 mIU/mL 1.13-12.51
IU/L
11. Active alcohol or substance abuse sufficient, in the Investigator's
judgment, to prevent adherence to study medication and/or follow-up;
12. Pregnant or nursing females;
13. Males whose female partner is pregnant;
14. Unwilling or unable to comply with the Lifestyle guidelines (eg, no
active drug or alcohol abuse);
15. Participation in other studies within 30 days before the current study
begins and/or during study participation;
16.Other severe acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with stud

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment of chronic HCV genotype 1 infection.
MedDRA version: 13.1 Level: LLT Classification code 10019752 Term: Hepatitis C virus (HCV) System Organ Class: 10022891 - Investigations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: FILIBUVIR
Product Code: PF-00868554
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Filibuvir
CAS Number: 877130-28-4
Current Sponsor code: PF-00868554
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: • Proportion of subjects with undetectable HCV RNA at Week 72 (SVR).

Secondary Objective: Secondary objectives include determination of the following :
•Proportion of subjects in Path 2 only with undetectable HCV RNA at
Weeks 4 (rapid viral response (RVR)), 12 (early viral response (EVR)),
24 and 48.
•Proportion of subjects with undetectable HCV RNA 12 weeks following
the completion of therapy (SVR12).
•Proportion of subjects in Path 1 only with undetectable HCV RNA 24
weeks following the completion of therapy (SVR24).
•Proportion of subjects with breakthrough or relapsed viremia in each
treatment arm.
•Assess the safety, tolerability and pharmacokinetics of filibuvir
administered in combination with pegIFN and RBV.

Main Objective: The primary objective for this study is to determine if the addition of
filibuvir to a SOC regimen of pegIFN/RBV significantly increases the
proportion of subjects who achieve a sustained viral response at the end
of study (SVR; defined as the proportion of subjects with an
undetectable plasma HCV RNA at Week 72) compared to pegIFN/RBV
therapy alone.

Primary end point(s): ? Proportion of subjects with undetectable HCV RNA at Week 72 (SVR).

Secondary Outcome(s)

Secondary end point(s): ? Proportion of subjects with undetectable HCV RNA at Weeks 4 (rapid
viral response; RVR), 12 (early viral response; EVR), 24 and 48 (Path 2
only);
? Proportion of subjects with undetectable HCV RNA 12 weeks following
the completion of therapy (SVR12);
? Proportion of subjects with undetectable HCV RNA 24 weeks following
the completion of therapy (SVR24; Path 1 only);
? Proportion of subjects with breakthrough viremia: >2-log increase
from nadir in HCV plasma RNA or HCV RNA that becomes undetectable
with treatment but becomes
persistently detectable (two or more consecutive viral RNA
measurements
>1,000 IU/mL) again during treatment;
? Proportion of subjects with relapsed response: HCV RNA that is
undetectable at end
of treatment (Week 24 or 48) that becomes detectable during the offtreatment
follow
up period;
? Change in HCV RNA concentrations from baseline at Week 4, 12 and
24;
? Safety: Severity and relationship of adverse events to test drug;
serious adverse
events; discontinuations due to adverse events; dose reductions due to
adverse events;
severity of abnormal laboratory values;
? Filibuvir, pegylated interferon and ribavirin concentrations.

Timepoint(s) of evaluation of this end point: As Above

Secondary ID(s)

A8121014

2009-009214-40-HU

Source(s) of Monetary Support

Pfizer Inc