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

NCT01023035 | Completed Phase 3 Results DMC

• 2 other identifiers: P060862009-012782-63
• Study Type: interventional
• Target: 687
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sustained Virologic Response (SVR)

  SVR was defined as undetectable plasma Hepatitis C Virus ribonucleic acid (HCV-RNA) at Follow-up Week 24

  At Follow-up Week 24

Secondary Outcomes (1)

• Percentage of Participants Who Discontinued Treatment

  From Study Day 1 up to Study Treatment Week 48

Study Arms (3)

Treated/Not Randomized

EXPERIMENTAL

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; Drug: Peginterferon alfa-2b (PEG2b); Drug: Ribavirin (RBV)

Ribavirin Dose Reduction

EXPERIMENTAL

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; Drug: Peginterferon alfa-2b (PEG2b); Drug: Ribavirin (RBV)

Erythropoietin Use

EXPERIMENTAL

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; Drug: Peginterferon alfa-2b (PEG2b); Drug: Ribavirin (RBV); Drug: Erythropoietin

Interventions

Boceprevir DRUG

800 mg given three times a day (TID), orally (PO)

Also known as: SCH 503034

Erythropoietin Use; Ribavirin Dose Reduction; Treated/Not Randomized

Peginterferon alfa-2b (PEG2b) DRUG

1.5 µg/kg/week given subcutaneously (SC)

Also known as: SCH 054031

Erythropoietin Use; Ribavirin Dose Reduction; Treated/Not Randomized

Ribavirin (RBV) DRUG

Ribavirin weight-based dosing (WBD), 600 to 1400 mg/day given twice daily (BID), orally (PO)

Also known as: SCH 018908, Rebetol

Erythropoietin Use; Ribavirin Dose Reduction; Treated/Not Randomized

Erythropoietin DRUG

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

Also known as: Procrit, Eprex

Erythropoietin Use

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Poordad F, Lawitz E, Reddy KR, Afdhal NH, Hezode C, Zeuzem S, Lee SS, Calleja JL, Brown RS Jr, Craxi A, Wedemeyer H, Nyberg L, Nelson DR, Rossaro L, Balart L, Morgan TR, Bacon BR, Flamm SL, Kowdley KV, Deng W, Koury KJ, Pedicone LD, Dutko FJ, Burroughs MH, Alves K, Wahl J, Brass CA, Albrecht JK, Sulkowski MS; Protocol 6086 Investigators. Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection--a randomized trial. Gastroenterology. 2013 Nov;145(5):1035-1044.e5. doi: 10.1053/j.gastro.2013.07.051. Epub 2013 Aug 4.

  PMID: 23924660 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; peginterferon alfa-2b; Ribavirin; Erythropoietin; Epoetin Alfa

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2009
• First Posted: December 1, 2009
• Study Start: December 7, 2009
• Primary Completion: October 26, 2011
• Study Completion: October 26, 2011
• Last Updated: February 8, 2021
• Results First Posted: November 15, 2012

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share