Boceprevir/Peginterferon/Ribavirin for Chronic Hepatitis C: Erythropoietin Use Versus Ribavirin Dose Reduction for Anemia (P06086 AM2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01023035
First received: November 24, 2009
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

The current trial is designed to prospectively explore the safety of erythropoietin use for the treatment of anemia during boceprevir plus peginterferon alfa-2b/Ribavirin (PEG2b/RBV) therapy and to assess its relationship to efficacy. All participants in this trial will be treated with the triple combination of boceprevir plus PEG2b/RBV. If a participant becomes anemic during treatment, the participant will be randomized to one of two therapeutic strategies for management of anemia (erythropoietin use versus RBV dose reduction).


Condition Intervention Phase
Hepatitis C, Chronic
Drug: Boceprevir
Drug: Peginterferon alfa-2b (PEG2b)
Drug: Ribavirin (RBV)
Drug: Erythropoietin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Boceprevir and Peginterferon/Ribavirin for the Treatment of Chronic Hepatitis C in Treatment-Naive Subjects: A Comparison of Erythropoietin Use Versus Ribavirin Dose Reduction for the Management of Anemia

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Virologic Response (SVR) [ Time Frame: At Follow-up Week 24 ] [ Designated as safety issue: No ]
    SVR was defined as undetectable plasma Hepatitis C Virus ribonucleic acid (HCV-RNA) at Follow-up Week 24


Secondary Outcome Measures:
  • Percentage of Participants Who Discontinued Treatment [ Time Frame: From Study Day 1 up to Study Treatment Week 48 ] [ Designated as safety issue: Yes ]
    Cumulative discontinuation was defined as the sum of discontinuations due to adverse events, viral breakthrough/resistance, detectable HCV-RNA and futility rules (<2-log10 decline in HCV-RNA at Treatment Week 12, ≥ Lower Limit of Quantification [LLQ] HCV-RNA at Treatment Week 24), and other (noncompliance, withdrawal of consent, lost to follow-up).


Enrollment: 687
Study Start Date: December 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treated/Not Randomized
Participants received 4 weeks of PEG2b/RBV followed by 24 or 44 weeks of boceprevir plus PEG2b/RBV depending on Hepatitis C Virus RNA (HCV-RNA) levels. Participants continued with this treatment if their serum hemoglobin remained >10 g/dL throughout the 28- or 48-week treatment period.
Drug: Boceprevir
800 mg given three times a day (TID), orally (PO)
Other Name: SCH 503034
Drug: Peginterferon alfa-2b (PEG2b)
1.5 µg/kg/week given subcutaneously (SC)
Other Name: SCH 054031
Drug: Ribavirin (RBV)
Ribavirin weight-based dosing (WBD), 600 to 1400 mg/day given twice daily (BID), orally (PO)
Other Name: SCH 018908, Rebetol
Experimental: Ribavirin Dose Reduction
After the initiation of treatment with 4 weeks with PEG2b/RBV followed by 24 or 44 weeks of boceprevir, participants who became anemic (serum hemoglobin = ≤10 g/dL) within the 28- or 48-week treatment period and who were randomized to the Ribavirin (RBV) Dose Reduction Arm received reduced doses of RBV for management of the anemia in combination with PEG2b and boceprevir therapies.
Drug: Boceprevir
800 mg given three times a day (TID), orally (PO)
Other Name: SCH 503034
Drug: Peginterferon alfa-2b (PEG2b)
1.5 µg/kg/week given subcutaneously (SC)
Other Name: SCH 054031
Drug: Ribavirin (RBV)
Ribavirin weight-based dosing (WBD), 600 to 1400 mg/day given twice daily (BID), orally (PO)
Other Name: SCH 018908, Rebetol
Experimental: Erythropoietin Use
After the initiation of treatment with 4 weeks with PEG2b/RBV followed by 24 or 44 weeks of boceprevir, participants who became anemic (serum hemoglobin = ≤10 g/dL) within the 28- or 48-week treatment period and who were randomized to the Erythropoietin Use Arm received erythropoietin for management of the anemia in addition to PEG2b/RBV and boceprevir therapies.
Drug: Boceprevir
800 mg given three times a day (TID), orally (PO)
Other Name: SCH 503034
Drug: Peginterferon alfa-2b (PEG2b)
1.5 µg/kg/week given subcutaneously (SC)
Other Name: SCH 054031
Drug: Ribavirin (RBV)
Ribavirin weight-based dosing (WBD), 600 to 1400 mg/day given twice daily (BID), orally (PO)
Other Name: SCH 018908, Rebetol
Drug: Erythropoietin
Initial dose of 40,000 Units given subcutaneously (SC) once weekly (QW), with dose adjustment as necessary to achieve and maintain serum hemoglobin levels of 10-12 g/dL
Other Name: Procrit, Eprex

  Eligibility

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

Inclusion Criteria:

  • Participant must have previously documented Chronic Hepatitis C (CHC) genotype 1 infection.
  • Hemoglobin concentration at Screening must be ≤15 g/dL for both females and males.
  • Participant must have a liver biopsy with histology consistent with CHC and no other etiology.
  • Participant with bridging fibrosis (F3) or cirrhosis (F4) must have an ultrasound within 6 months of the Screening Visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma.
  • Participant's weight must be ≥40 kg and ≤125 kg.
  • Participant and participant'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 medication, or longer if dictated by local regulations.
  • Participant must be willing to give written informed consent.
  • Participant must be willing to attend frequent site visits for the duration of the trial.
  • Participant must not have any contraindications for the use of erythropoietin.

Exclusion Criteria:

  • Participants known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus.
  • Participants who received prior treatment for hepatitis C.
  • Treatment with any investigational drug within 30 days of the screening visit in this trial.
  • Participants receiving any of the following medication(s) within 2 weeks prior to the Day 1 visit: alfuzosin, antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, and quinidine), ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, triazolam, and orally administered midazolam.
  • Participation in any other clinical trial within 30 days of the screening visit in this trial or intention to participate in another clinical trial during participation in this trial.
  • Evidence of decompensated liver disease.
  • Diabetic and/or hypertensive participants with clinically significant ocular examination findings.
  • Pre-existing psychiatric condition(s).
  • Clinical diagnosis of substance abuse of specified drugs within specified timeframes.
  • Any known pre-existing medical condition that could interfere with the participant's participation in and completion of the trial.
  • 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).
  • Participants who are pregnant or nursing. Participants who intend to become pregnant during the trial period. Male participants with partners who are, or intend to become, pregnant during the trial period.
  • Any other condition which, in the opinion of a physician, would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the trial.
  • Participant who had a life-threatening serious adverse event during the screening period.
  • A participant must not be a member or a family member of the personnel of the investigational or sponsor staff directly involved with this trial.
  • Protocol-specified hematologic, biochemical, and serologic criteria (growth factors may not be used to achieve trial entry requirements).
  • Serum albumin below the lower limit of normal (LLN) of laboratory reference range.
  • Thyroid-stimulating hormone (TSH) >1.2 x Upper Limit of Normal (ULN) or <0.8 x LLN of laboratory reference.
  • 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.
  • Protocol-specified alpha fetoprotein concentrations.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01023035     History of Changes
Other Study ID Numbers: P06086, 2009-012782-63
Study First Received: November 24, 2009
Results First Received: October 16, 2012
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Epoetin alfa
Ribavirin
Peginterferon alfa-2b
Interferon-alpha
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 31, 2014