Clinical trial NCT01457937: Boceprevir/PegIFN α-2b/Riba in HCV+ Gt1 Menopausal Women, Nonresponders to PegIFN/Riba or Treatment-naives (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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Hepatitis C
Menopause
Keywords: HCV
Menopause
Peg IFN
Ribavirin
Boceprevir
Lead sponsor: University of Modena and Reggio Emilia
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-10-24
Enrollment: 240
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Improvement of sustained virological response in previous treatment failure or naive HCV-positive menopausal women.
timeFrame: Baseline and 72 weeks
Secondary outcomes:
measure: Early virological response
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Modena
country: Italy
facility: Gastroenterology Unit
Study officials:
affiliation: Azienda Ospedaliero-Universitaria, University of Modena and Reggio Emilia
name: ERICA VILLA, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.