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

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2009-009214-40-BE
• Date of registration: 09/07/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public 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
• 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
• Date of first enrolment: 22/09/2009
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Hungary, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible 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 non-cirrhotic 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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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:
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. Part

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

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)

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.

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.

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

Secondary ID(s)

2009-009214-40-HU

A8121014