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

Menopause Clinical Trial

— MEN_BOC  

Official title:

Boceprevir/Peginterferon Alfa (PegIFN α)-2b/Ribavirin (Riba) in Difficult-to-Treat Menopausal Women With Chronic Hepatitis C Genotype 1 (Gt 1), Either Deemed Nonresponders to Peginterferon/Ribavirin or Treatment-naives (MEN_BOC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01457937
• Other study ID #: EudraCT 2011-002459-33
• Status: Recruiting
• Phase: Phase 3
• First received: October 8, 2011
• Last updated: September 29, 2012
• Start date: November 2011
• Est. completion date: June 2014

Study information

• Verified date: September 2012
• Source: University of Modena and Reggio Emilia
• Contact: Erica Villa, Prof.
• Phone: +390594225308
• Email: erica.villa[@]unimore.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: June 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Menopause

Intervention

Drug:
• 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)

Locations

Country	Name	City	State
Italy	Gastroenterology Unit	Modena

Sponsors (2)

Lead Sponsor	Collaborator
University of Modena and Reggio Emilia	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of sustained virological response in previous treatment failure or naive HCV-positive menopausal women.	Verify whether the SVR (HCV RNA undetectable at 24 wks) in menopausal women with HCV CAH genotype 1 with a previous failure with PEG IFN/ribavirin or treatmenti-naive may increase by 20% or 25% respectively after treatment with PEG IFN alfa 2b and boceprevir (1.5 mcg / kg QW) + Ribavirin (800-1400 mg / day).	Baseline and 72 weeks	Yes
Secondary	Early virological response	Evaluation of the percent of patients with early virological response (undetectable HCV RNA at weeks 2, 4, 8 or 12) that reach SVR	Baseline and 12 weeks	Yes