Clinical Trials Register

Summary
EudraCT Number:	2009-009214-40
Sponsor's Protocol Code Number:	A8121014
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-12-11
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2009-009214-40

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Filibuvir in Treatment Naïve HCV Genotype 1 Subjects

A.3.2

Name or abbreviated title of the trial where available

FITNESS

A.4.1

Sponsor's protocol code number

A8121014

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pfizer Inc, 235 East 42nd Street, New York, NY 10017, USA
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pfizer Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pfizer Inc
B.5.2	Functional name of contact point	Clinical Trials.gov Call Center
B.5.3	Address:
B.5.3.1	Street Address	235 East 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017
B.5.3.4	Country	United States
B.5.4	Telephone number	+18007181021
B.5.5	Fax number	+1303739 1119
B.5.6	E-mail	ClinicalTrials.govCallCentrere@pfizer.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	FILIBUVIR
D.3.2	Product code	PF-00868554
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Filibuvir
D.3.9.1	CAS number	877130-28-4
D.3.9.2	Current sponsor code	PF-00868554
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Treatment of chronic HCV genotype 1 infection.

E.1.1.1

Medical condition in easily understood language

Hepatitis C Virus Infection

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	LLT
E.1.2	Classification code	10019752
E.1.2	Term	Hepatitis C virus (HCV)
E.1.2	System Organ Class	10022891 - Investigations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A8121014, Semen sub-study , 02 September 09
A PARALLEL GROUP SUB-STUDY TO ASSESS THE EFFECT OF FILIBUVIR ON SEMEN AND REPRODUCTIVE HORMONE PARAMETERS IN TREATMENT NAÏVE, MALE HCV GENOTYPE 1 INFECTED SUBJECTS
Objective
 To evaluate the effects of filibuvir (300 or 600 mg BID) administered in combination with SOC therapy compared to SOC therapy alone on semen parameters in treatment naïve, male HCV genotype 1 infected subjects.

E.3

Principal 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.

E.4

Principal 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 study
participation or investigational product administration or may interfere
with the interpretation of study results and, in the judgment of the
investigator, would make the subject inappropriate for entry into this
study.
NOTE: Subjects with laboratory values outside of the criteria specified
above may be retested once only. If upon retest a laboratory value is
within 10% of the criteria listed above, the investigator may consider
the subject for enrolment so long as the laboratory value is not
considered by the investigator to be clinically significant.

E.5 End points

E.5.1

Primary end point(s)

 Proportion of subjects with undetectable HCV RNA at Week 72 (SVR).

E.5.1.1

Timepoint(s) of evaluation of this end point

• Proportion of subjects with undetectable HCV RNA at Week 72 (SVR).

E.5.2

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.

E.5.2.1

Timepoint(s) of evaluation of this end point

As Above

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Canada

France

Germany

Hungary

Korea, Republic of

Puerto Rico

Spain

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

In protocol

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1