Hepatitis C, ChronicPhase 3NCT01023035

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

A Phase 3 study testing Boceprevir, Peginterferon alfa-2b (PEG2b) and Ribavirin (RBV) in people with Hepatitis C, Chronic, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatitis C, Chronic
What is being tested?: Boceprevir, Peginterferon alfa-2b (PEG2b) and Ribavirin (RBV)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 687 participants
Where: No sites listed yet
Study dates: 7 Dec 2009to 26 Oct 2011
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 9Show fewer

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.

Who cannot join

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.

Show all 22Show fewer

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.

About this study

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

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
Being tested: Boceprevir, Peginterferon alfa-2b (PEG2b), Ribavirin (RBV), Erythropoietin
Medical subject headings: Hepatitis C, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BoceprevirDrug
Also called SCH 503034
800 mg given three times a day (TID), orally (PO)
Peginterferon alfa-2b (PEG2b)Drug
Also called SCH 054031
1.5 µg/kg/week given subcutaneously (SC)
Ribavirin (RBV)Drug
Also called SCH 018908, Rebetol
Ribavirin weight-based dosing (WBD), 600 to 1400 mg/day given twice daily (BID), orally (PO)
ErythropoietinDrug
Also called Procrit, Eprex
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

Study groups in NCT01023035
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: Boceprevir; Drug: Peginterferon alfa-2b (PEG2b); Drug: Ribavirin (RBV); Drug: Erythropoietin

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: At Follow-up Week 24

Secondary outcomes (1)

Percentage of Participants Who Discontinued Treatment
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).
Measured: From Study Day 1 up to Study Treatment Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Dec 200926 Oct 2011

First posted1 Dec 2009 (estimated)
Study start7 Dec 2009
Primary completion26 Oct 2011
Study completion26 Oct 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatitis C, ChronicStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 687 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01023035
Sponsor's protocol ID: P06086
Other IDs: 2009-012782-63, 2009
Status last verified: Jan 2021
First submitted: 24 Nov 2009
Last updated: 8 Feb 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

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.
PubMed 23924660

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

All Hepatitis C, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01023035
Acronym / sponsor ID: P06086
Conditions: Hepatitis C, Chronic
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 687 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 7 Dec 2009 (actual)
Primary completion: 26 Oct 2011 (actual)
Study completion: 26 Oct 2011 (actual)
First posted: 1 Dec 2009 (estimated)
Results: Posted 15 Nov 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Treated/Not Randomized	Experimental	Drug: Boceprevir, Drug: Peginterferon alfa-2b (PEG2b), Drug: Ribavirin (RBV)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.
Ribavirin Dose Reduction	Experimental	Drug: Boceprevir, Drug: Peginterferon alfa-2b (PEG2b), Drug: Ribavirin (RBV)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.
Erythropoietin Use	Experimental	Drug: Boceprevir, Drug: Peginterferon alfa-2b (PEG2b), Drug: Ribavirin (RBV), Drug: ErythropoietinAfter 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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.

Key exclusion criteria (22 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BoceprevirAlso: SCH 503034800 mg given three times a day (TID), orally (PO)	Drug	Erythropoietin Use, Ribavirin Dose Reduction, Treated/Not Randomized
Peginterferon alfa-2b (PEG2b)Also: SCH 0540311.5 µg/kg/week given subcutaneously (SC)	Drug	Erythropoietin Use, Ribavirin Dose Reduction, Treated/Not Randomized
Ribavirin (RBV)Also: SCH 018908, RebetolRibavirin weight-based dosing (WBD), 600 to 1400 mg/day given twice daily (BID), orally (PO)	Drug	Erythropoietin Use, Ribavirin Dose Reduction, Treated/Not Randomized
ErythropoietinAlso: Procrit, EprexInitial 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	Drug	Erythropoietin Use

Primary outcome

Percentage of Participants With Sustained Virologic Response (SVR)
Time frame: At Follow-up Week 24
SVR was defined as undetectable plasma Hepatitis C Virus ribonucleic acid (HCV-RNA) at Follow-up Week 24

1 secondary outcome

Percentage of Participants Who Discontinued Treatment
Time frame: From Study Day 1 up to Study Treatment Week 48

Results and safety

Results posted to the registry on 15 Nov 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ribavirin Dose Reduction Arm	249	177
Erythropoietin Use Arm	251	166
Treated/Not Randomized	187	69

Primary outcome: Percentage of Participants With Sustained Virologic Response (SVR)

Time frame: At Follow-up Week 24. Number. Unit: percentage of participants

Measure	Ribavirin Dose Reduction Arm n = 249	Erythropoietin Use Arm n = 251
Value	71.5	70.9

Ribavirin Dose Reduction Arm vs Erythropoietin Use Arm: Mean Difference (Final Values): -0.7 (95% CI -8.6 to 7.2), Mantel-Haenszel, modified Koch method

Population analysed: The primary efficacy analysis was performed on all participants who were randomized to either the RBV Dose Reduction Arm or the EPO Use Arm for anemia management (i.e. the Full Analysis Set of patients requiring anemia management \[FAS, n=500\]).

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ribavirin Dose Reduction Arm	39 of 249 (15.7%)	247 of 249 (99.2%)	Not reported
Erythropoietin Use Arm	33 of 251 (13.1%)	248 of 251 (98.8%)	Not reported
Treated/Not Randomized	15 of 187 (8%)	180 of 187 (96.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23924660Poordad 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.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Related trials for Hepatitis C, Chronic

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Boceprevir, Peginterferon alfa-2b (PEG2b) and Ribavirin (RBV) in people with Hepatitis C, Chronic, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Sustained Virologic Response (SVR) (time frame: At Follow-up Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01023035, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2021.