Boceprevir/PegIFN α-2b/Riba in HCV+ Gt1 Menopausal Women, Nonresponders to PegIFN/Riba or Treatment-naives (MEN_BOC)

NCT ID: NCT01457937

Last Updated: 2012-10-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2014-06-30

Brief Summary

The cohort of post-menopausal women represents a group of very-difficult-to-treat patients in whom a more powerful approach is required in order to improve the disappointing response rate. Thus the addition, in patients with previous failure to PEG/RBV treatment or in naïve patients, of a powerful drug like Boceprevir could greatly improve SVR rate as suggested by the results of SPRINT_2 trial in whom Boceprevir addition determined a 30% improvement in SVR rate in difficult gt 1 patients of African descent versus standard PEG IFN/Ribavirin therapy or by those of RESPOND-2 that showed the same percent improvement of RGT-retreatment with Boc/P/R of previous failure of standard therapy.

Goal of the study is to verify whether the addition of a 24-week treatment with boceprevir to standard antiviral therapy with Peg IFN and ribavirin will increase the rate of SVR in patients difficult to treat, such as HCV-positive women in post-menopausal women with genotype 1, not only those who have never been treated, but also in those who have not responded to previous treatment with peginterferon and ribavirin (Riba).

Detailed Description

2.2.1 Hypothesis Our hypothesis is that the addition of a 24-week treatment with boceprevir to standard antiviral therapy with Peg IFN and ribavirin will increase the rate of sustained virological response (SVR) in patients difficult to treat, such as HCV-positive women in post-menopausal women with genotype 1, not only those who have never been treated, but also in those who have not responded to previous treatment with peginterferon and ribavirin (Riba) Objectives Retreatment Primary objective Verify whether the sustained virological response (SVR defined as HCV RNA undetectable at 24 weeks of follow-up) in menopausal women with HCV CAH genotype 1 who have not achieved a sustained virological response with a previous treatment with PEG IFN/ribavirin may increase by at least 20% after treatment with PEG IFN alfa 2b and boceprevir (1.5 mcg / kg QW) + Ribavirin (800-1400 mg / day) The primary efficacy endpoint, achieving SVR, will be evaluated with descriptive statistics (n,%) for each treatment arm.

Secondary objective It is represented by evaluation of the percent of patients with early virological response (undetectable HCV RNA at weeks 2, 4, 8 or 12) that reach SVR.

Naïve patients

Primary objective Verify whether SVR, defined as undetectable HCV-RNA at 24 weeks of follow-up may increase by at least 25% after treatment with PEG IFN alfa 2b plus ribavirin and boceprevir vs. PEG IFN alfa 2b plus ribavirin alone, in postmenopausal women with CHC genotype 1 not previously treated The primary efficacy endpoint, achieving SVR, will be evaluated with descriptive statistics (n,%) for each treatment arm.

Secondary objective It is represented by evaluation of the percent of patients with early virological response (undetectable HCV RNA at weeks 2, 4, 8 or 12) that reach SVR.

Conditions

Chronic Hepatitis C; Menopause

Keywords

HCV; Menopause; Peg IFN; Ribavirin; Boceprevir

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PEG IFN/Ribavirin

Standard of care for HCV-positive CAH

Group Type: ACTIVE_COMPARATOR

Pegylated Interferon, Ribavirin, Boceprevir

Intervention Type: DRUG

PEG IFN alfa 2b 1,5 ug/kg once weekly; Ribavirin (800-1400 mg / day)

or

PEG IFN alfa 2b 1,5 ug/kg once weekly; Ribavirin (800-1400 mg / day); Boceprevir (1.5 mcg / kg QW)

PEG IFN/Ribavirin/Boceprevir

Combination to be tested for possible higher efficacy

Group Type: EXPERIMENTAL

Pegylated Interferon, Ribavirin, Boceprevir

Intervention Type: DRUG

PEG IFN alfa 2b 1,5 ug/kg once weekly; Ribavirin (800-1400 mg / day)

or

PEG IFN alfa 2b 1,5 ug/kg once weekly; Ribavirin (800-1400 mg / day); Boceprevir (1.5 mcg / kg QW)

Interventions

Pegylated Interferon, Ribavirin, Boceprevir

PEG IFN alfa 2b 1,5 ug/kg once weekly; Ribavirin (800-1400 mg / day)

or

PEG IFN alfa 2b 1,5 ug/kg once weekly; Ribavirin (800-1400 mg / day); Boceprevir (1.5 mcg / kg QW)

Intervention Type: DRUG

Other Intervention Names

PEG IFN alfa 2b : Peg Intron; Ribavirin: Rebetol; Boceprevir: Victrelis

Eligibility Criteria

Inclusion Criteria

• Menopausal females with previously documented CHC infection, either (A) relapser or with a >2log10 IU/ml HCV RNA decrease at week 12 in a previous PEG IFN/Ribavirin treatment or (B) naives;
• Subject must have a liver biopsy within the last 2 years with histology consistent with CHC and no other etiology.
• 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).
• Subject must be willing to give written informed consent.

Exclusion Criteria

• Coinfection with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive).
• 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 clinical ascites, bleeding varices, or hepatic encephalopathy.
• Diabetic and/or hypertensive subjects with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality.
• Pre-existing psychiatric condition(s).
• Clinical diagnosis of substance abuse of the specified drugs within the specified timeframes.
• Any known pre-existing medical condition that could interfere with the subject's participation in and completion of the study.
• 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 had life-threatening serious adverse event (SAE) during screening period.
• Protocol-specified hematologic, biochemical, and serologic criteria: Hemoglobin <12 g/dL for females and <13 g/dL for males; Neutrophils <1500/mm^3 (blacks: <1200/mm^3); Platelets <100,000/mm^3; Direct bilirubin >1.5 x upper limit of normal (ULN)
• Serum albumin < lower limit of normal (LLN)
• Thyroid-stimulating hormone (TSH) >1.2 x ULN or <0.8 x LLN of laboratory, with certain exceptions.
• Serum creatinine >ULN of the laboratory reference.
• Protocol-specified serum glucose concentrations.
• Prothrombin time/partial thromboplastin time (PT/PTT) values >10% above laboratory reference range.
• Anti-nuclear antibodies (ANA) >1:320.

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Modena and Reggio Emilia

OTHER

Sponsor Role: lead

Responsible Party

Prof. Facchinetti Fabio

Prs admin

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

ERICA VILLA, Prof

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliero-Universitaria, University of Modena and Reggio Emilia

Locations

Gastroenterology Unit

Modena, Modena, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Erica Villa, Prof.

Role: CONTACT

Phone: +390594225308

Email: erica.villa@unimore.it

Annalisa Berselli, B Sc

Role: CONTACT

Phone: +390594223045

Email: annalisa.berselli@unimore.it

Facility Contacts

Erica Villa, Prof.

Role: primary

Annalisa Bersellii, B Sc

Role: backup

References

Bernabucci V, Ciancio A, Petta S, Karampatou A, Turco L, Strona S, Critelli R, Todesca P, Cerami C, Sagnelli C, Rizzetto M, Camma C, Villa E. Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women. World J Gastroenterol. 2014 Nov 28;20(44):16726-33. doi: 10.3748/wjg.v20.i44.16726.

Reference Type: DERIVED

PMID: 25469044 (View on PubMed)

Other Identifiers

EudraCT 2011-002459-33

Identifier Type: -

Identifier Source: org_study_id