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Safety and Efficacy of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1 (Study P05216AM1) (SPRINT-2)
This study is currently recruiting participants.
Verified by Schering-Plough, December 2008
Sponsored by: Schering-Plough
Information provided by: Schering-Plough
ClinicalTrials.gov Identifier: NCT00705432
  Purpose

This study involves treatment with boceprevir or placebo in combination with PegIntron (PEG) + Ribavirin (RBV) (weight-based dosing [WBD]) in previously untreated adult subjects with chronic hepatitis C (CHC) genotype 1. This trial includes three arms, all of which have a 4-week lead-in period with PEG + RBV. There is one control arm (PEG + RBV + boceprevir placebo) for 44 weeks after the lead-in, and two experimental arms (PEG + RBV + boceprevir). One of the experimental arms consists of treatment with all three drugs for 44 weeks after the lead-in. The other experimental arm consists of all three drugs for 24 weeks after the lead-in. Those subjects in the second experimental arm who were undetectable for HCV-RNA at week 8 will complete treatment at that point. Those who were not undetectable for HCV-RNA at week 8 will receive an additional 20 weeks of PEG + RBV + boceprevir placebo. It is hypothesized that the addition of a third active anti-HCV drug may lead to more rapid viral response than therapy with two drugs, and therefore, the addition of boceprevir to PegIntron plus ribavirin therapy after a 4-week lead-in period may allow for both increased rates of SVR and shorter treatment durations (in some populations) than treatment with PegIntron/ribavirin alone.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: Boceprevir (SCH 503034)
Biological: Peginterferon alfa-2b (SCH 54031)
Drug: Ribavirin (SCH 18908)
Drug: Boceprevir placebo
Phase III

MedlinePlus related topics: Hepatitis Hepatitis C
Drug Information available for: Ribavirin Peginterferon Alfa-2b Boceprevir
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase 3, Safety and Efficacy Study of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1

Further study details as provided by Schering-Plough:

Primary Outcome Measures:
  • Sustained virologic response (SVR), defined as undetectable plasma HCV-RNA at Follow-up Week 24, after treatment with boceprevir and PegIntron plus ribavirin or PegIntron plus ribavirin alone in previously untreated subjects with CHC genotype 1. [ Time Frame: At Follow-up Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects with early virologic response (undetectable HCV-RNA at Treatment Week 2, 4, 8, or 12) who achieved SVR. [ Time Frame: At Treatment Week 2, 4, 8, or 12 ] [ Designated as safety issue: No ]
  • Proportions of subjects with undetectable HCV-RNA at Follow-up Week 12 and at 72 weeks after randomization. [ Time Frame: At Follow-up Week 12 and at 72 weeks after randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 1080
Study Start Date: August 2008
Estimated Study Completion Date: October 2010
Estimated Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm 1: Placebo Comparator
PegIntron (PEG) 1.5 μg/kg + Ribavirin (RBV) (weight-based dosing [WBD]) for 4 weeks followed by placebo + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.
Biological: Peginterferon alfa-2b (SCH 54031)
Peginterferon alfa-2b 1.5 μg/kg/week subcutaneously (SC)
Drug: Ribavirin (SCH 18908)
Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day PO divided twice daily (BID).
Drug: Boceprevir placebo
Boceprevir placebo, 200 mg capsules, 800 mg TID PO.
Arm 2: Experimental

PEG 1.5 μg/kg + RBV (WBD) for 4 weeks followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 24 weeks.

  • At the Treatment Week 28 visit, subjects whose HCV-RNA was undetectable at Treatment Week 8 and at all subsequent assays will proceed to the 44-week follow-up.
  • At the Treatment Week 28 visit, subjects with detectable HCV-RNA at Treatment Week 8 or at any subsequent assays will continue on therapy with placebo + PEG 1.5 μg/kg + RBV (WBD) for an additional 20 weeks, to complete a total of 48 weeks on treatment with 24 weeks post-treatment follow-up.
Drug: Boceprevir (SCH 503034)
Boceprevir, 200 mg capsules, 800 mg three times a day (TID) orally (PO).
Biological: Peginterferon alfa-2b (SCH 54031)
Peginterferon alfa-2b 1.5 μg/kg/week subcutaneously (SC)
Drug: Ribavirin (SCH 18908)
Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day PO divided twice daily (BID).
Drug: Boceprevir placebo
Boceprevir placebo, 200 mg capsules, 800 mg TID PO.
Arm 3: Experimental
PEG 1.5 μg/kg + RBV (WBD) for 4 weeks followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.
Drug: Boceprevir (SCH 503034)
Boceprevir, 200 mg capsules, 800 mg three times a day (TID) orally (PO).
Biological: Peginterferon alfa-2b (SCH 54031)
Peginterferon alfa-2b 1.5 μg/kg/week subcutaneously (SC)
Drug: Ribavirin (SCH 18908)
Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day PO divided twice daily (BID).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must have previously documented CHC genotype 1 infection.
  • Subject must have a liver biopsy 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 >=18 years of age.
  • Subject must weigh between 40 kg and 125 kg.
  • Subject and subject's partner(s) must each agree to use acceptable methods of contraception 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.
  • Subjects must be willing to give written informed consent.

Exclusion Criteria:

  • Coinfection with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive).
  • Subjects who received prior treatment for hepatitis C; other than herbal remedies, except those with known hepatotoxicity.
  • 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 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.
  • 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.
  • protocol-specified alpha fetoprotein levels.
  • Prothrombin time/partial thromboplastin time (PT/PTT) values >10% above laboratory reference range.
  • Anti-nuclear antibodies (ANA) >1:320.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00705432

Contacts
Contact: SP Clinical Trial Registry Call Center 1-888-772-8734

  Show 128 Study Locations
Sponsors and Collaborators
Schering-Plough
  More Information

Responsible Party: Schering-Plough ( Head, Clinical Trials Registry & Results Disclosure Group )
Study ID Numbers: P05216, EUDRACT # 2007-005508-42
Study First Received: June 24, 2008
Last Updated: December 15, 2008
ClinicalTrials.gov Identifier: NCT00705432  
Health Authority: United States: Food and Drug Administration

Study placed in the following topic categories:
Interferon-alpha
Liver Diseases
Hepatitis, Chronic
Interferons
Ribavirin
Hepatitis, Viral, Human
Hepatitis
Virus Diseases
Digestive System Diseases
Peginterferon alfa-2b
Hepatitis C
Interferon Alfa-2a
Hepatitis C, Chronic
Interferon Alfa-2b

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Flaviviridae Infections
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on January 16, 2009