A Phase 3 Safety and Efficacy Study of Boceprevir in Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin

• Register: EUCTR
• Last refreshed on: 20 May 2013
• Main ID: EUCTR2007-005151-42-DE
• Date of registration: 22/08/2008
• Prospective Registration: Yes
• Primary sponsor: Schering Plough Research Institute, A Division of Schering Corporation
• Public title: A Phase 3 Safety and Efficacy Study of Boceprevir in Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin
• Scientific title: A Phase 3 Safety and Efficacy Study of Boceprevir in Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin
• Date of first enrolment: 22/09/2008
• Target sample size: 375
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005151-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium, France, Germany, Italy, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria for interferon responsive CHC patients who have failed treatment:
1. For inclusion in the study, subjects must have a qualifying regimen defined as peginterferon alfa-2a plus ribavirin or peginterferon alfa-2b plus ribavirin for a minimum of 12 weeks. If a subject has received more than one such regimen, the most recent regimen is considered the qualifying regimen.
Note: Prior maintenance therapy, following failure of qualifying therapy, with any interferon alpha is acceptable; subject must discontinue maintenance therapy 1 month prior to the screening visit.

2. During qualifying regimen, subjects must have either:
a. a documented undetectable HCV-RNA level within 30 days of EOT and a subsequent detectable HCV-RNA during follow-up OR
b. a documented decline in HCV-RNA by greater than or equal to 2log10 by TW 12
Note: For subjects who did not participate in SPRI protocols, qualifying virology reports and documentation of qualifying previous treatment regimen must be completely de-identified and faxed to the sponsor's project physician for confirmation that the subject qualifies for this study.

3. Subject must have documented CHC genotype 1 infection. The HCV-RNA result obtained from the central laboratory at the screening visit must confirm genotype 1 infection and be >10,000 IU/mL. Subjects with other or mixed genotypes are not eligible.

4. Subject must have a liver biopsy with histology consistent with CHC and no other etiology. Copies of the pathology report and slides are required for the subject to be included in the study. The pathology report and histology slides must be available at the study site prior to subject randomization.Two unstained slides are preferred; however, one slide stained with hematoxylin plus eosin (H & E) plus one slide stained with Masson’s trichrome will be accepted (slides should be reviewed by the investigator to confirm adequacy). The central pathologist reading will be used for analysis purposes.
a. No cirrhosis: Biopsy must be within 3 years of the Screening visit. For biopsies performed more than 18 months prior to the Screening visit, fibrosis marker testing will be performed to assess level of fibrosis;
b. Cirrhosis: Any historic liver biopsy demonstrating cirrhosis will be sufficient regardless of length of time since biopsy.

5. Subjects with bridging fibrosis or cirrhosis must have an ultrasound within 6 months of the Screening visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma (HCC).

6. Subjects participating in SPRI maintenance protocols P02570 or P02569 must have been compliant with, and completed all study related requirements to be eligible for this protocol.

General Inclusion Criteria
7. Subject must be 18 years old or older.

8. Subject must weigh between 40 kg and 125 kg.

9. Subject and subject’s partner(s) must each agree to use acceptable methods of contraception as specified in Section 7.6.1 for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations.

10. Subjects must be willing to give written informed consent.

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 known to be co-infected with HIV or hepatitis B virus (HBsAg positive), or infected with HCV genotypes other than genotype 1 (including mixed genotypes)
-Subjects who required discontinuation of peg/rbv for an adverse event considered by the investigator to be possibly or probably related to ribavirin and/or interferon during any previous therapy with interferon and ribavirin
-Treatment with ribavirin within 90 days and any interferon-alpha within 1 month of Screening
-Treatment for CHC with any investigational medication. All herbal remedies used for CHC treatment other than silymarin (milk thistle) must be discontinued before Day 1.
-Treatment with any investigational drug within 30 days of the randomization visit in this study
-Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study
-Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
-Diabetic and hypertensive subjects with clinically significant ocular examination findings as defined in the protocol
-Pre-existing psychiatric condition(s) as defined in protocol
-Clinical diagnosis of substance abuse as defined in the protocol by drug type and timeframe
-As further defined in the protocol, any known pre-existing medical condition that could interfere with the subject’s participation in and completion of the study including but not limited to:
a. Central nervous system (CNS) trauma
b. Current or history of seizure disorder
c. History of stroke or transient ischemic attack
d. Immunologically-mediated disease
e. Chronic pulmonary disease
f. Current or history of any clinically significant cardiac abnormalities/dysfunction
g. Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the study
h. Active clinical gout within the last year
i. Hemoglobinopathy
j. Myelodysplastic syndromes
k. Coagulopathy
l. Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair
m. Poor venous access that precludes routine peripheral blood sampling required for this study
n. Subjects with indwelling venous catheters
o. Subjects with a history of gastric surgery or subjects with a history of malabsorption disorders
-Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin). Subjects under evaluation for malignancy are not eligible.
-Subjects who are pregnant or nursing. Subjects who intend to become pregnant during the study period. Male subjects with partners who are, or intend to become, pregnant during the study period.
-Any other condition which, in the opinion of a physician, would make the subject unsuitable for enrollment or could interfere with the subject participating in and completing the study
-Subjects who are part of the site personnel directly involved with this study
-Subjects who are family members of the investigational study staff
-Subjects who had life-threatening serious adverse event (SAE) during screening period
Laboratory Exclusion Criteria
Note: If any of the laboratory exclusion criteria are met, then the site may have the subject retested for eligibility as described in the protocol
-Hematological, biochemical, and serologic criteria (growth factor

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

Health Condition(s) or Problem(s) studied

Chronic Hepatitis C
MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
MedDRA version: 9.1 Level: PT Classification code 10019744 Term: Hepatitis C
MedDRA version: 9.1 Level: SOC Classification code 10021881 Term: Infections and infestations
MedDRA version: 9.1 Level: SOC Classification code 10019805 Term: Hepatobiliary disorders

Intervention(s)

Product Code: SCH 503034
Pharmaceutical Form: Capsule*
INN or Proposed INN: Boceprevir
CAS Number: 394730-60-0
Current Sponsor code: SCH 503034
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Trade Name: PegIntron
Product Name: PegIntron
Product Code: SCH 54031
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: peginterferon alfa-2b
CAS Number: 215647-85-1
Current Sponsor code: SCH 54031
Other descriptive name: PegIntron
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Rebetol
Product Name: Rebetol
Product Code: SCH 18908
Pharmaceutical Form: Capsule*
INN or Proposed INN: Ribavirin
Current Sponsor code: SCH 18908
Other descriptive name: Rebetol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: PegIntron
Product Name: PegIntron
Product Code: SCH 54031
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: peginterferon alfa-2b
CAS Number: 215647-85-1
Current Sponsor code: SCH 54031
Other descriptive name: PegIntron
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 80-

Trade Name: PegIntron
Product Name: PegIntron
Product Code: SCH 54031
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: peginterferon alfa-2b
CAS Number: 215647-85-1
Current Sponsor code: SCH 54031
Other descriptive name: PegIntron
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 120-

Trade Name: PegIntron
Product Name: PegIntron
Product Code: SCH 54031
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: peginterferon alfa-2b
CAS Number: 215647-85-1
Current Sponsor code: SCH 54031
Other descriptive name: PegIntron
Concentration unit: µg microgram(s)
Concentra

Primary Outcome(s)

Main Objective: The primary objective of this study is to compare the efficacy of two therapeutic regimens of boceprevir 800 mg three times a day (TID) orally (PO) (hereafter called boceprevir) in combination with PegIntron™ 1.5 µg/kg weekly (QW) subcutaneously (SC) plus weight-based dosing (WBD) of ribavirin (600 mg/day to 1400 mg/day) PO (hereafter called PEG + RBV [WBD]) to therapy with PEG + RBV [WBD] alone in adult subjects with chronic hepatitis C (CHC) genotype 1 with demonstrated interferon responsiveness who failed prior treatment with peginterferon/ribavirin.

Primary end point(s): The primary efficacy endpoint is the achievement of SVR, defined as undetectable plasma HCV-RNA at FW 24. Subjects will be declared treatment failures in one of the following ways:
• Subjects in any treatment arm with detectable HCV-RNA at FW 24.
• Subjects in any treatment arm with detectable HCV-RNA at TW 12.
• Subjects in any treatment arm who are missing their HCV-RNA at FW 24 with detectable HCV-RNA at FW 12.

Secondary Objective: The key secondary objective of this study is to compare the efficacy of two therapeutic regimens of boceprevir when used in combination with PEG+RBV (WBD) with standard of care (PEG +RBV [WBD] alone) in randomized subjects who recieved at least one dose of experimental study drug (placebo for the control arm and boceprevir for the experimental arms).

1) To evaluate the safety of boceprevir when used in combination with PEG + RBV (WBD).

2) To define predictors of sustained virologic response (SVR) such as epidemiologic factors, disease characteristics and on-treatment response.

3) To develop the relationship between steady state pharmacokinetic parameters, obtained from a population based pharmacokinetic model and responses in a subset of subjects.

Secondary ID(s)

P05101

2007-005151-42-FR