Hepatitis C, ChronicPhase 3NCT00845065
Boceprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Participants With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin (Study P05685AM2)(COMPLETED)
A Phase 3 study testing Boceprevir, Peginterferon alfa-2a and Ribavirin in people with Hepatitis C, Chronic, run by Merck Sharp & Dohme LLC.
Trial summary
Based on previous experience with peginterferon alfa-2b/ribavirin in combination with boceprevir, the combination with peginterferon alfa- 2a/ribavirin and boceprevir is expected to be safe and well tolerated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Chronic
- What is being tested?
- Boceprevir, Peginterferon alfa-2a and Ribavirin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 202 participants
- Where
- No sites listed yet
- Study dates
- Feb 2009to Oct 2010
- 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
- Subjects must have a qualifying regimen defined as peginterferon alfa-2a/ribavirin or peginterferon alfa-2b/ribavirin for a minimum of 12 weeks.
- During the qualifying regimen, subjects must have either:
- A documented undetectable Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) within 30 days of the end-of-treatment and a subsequent detectable HCV-RNA during follow-up OR
- A documented decline in HCV-RNA by >=2 log10 after 12 weeks of treatment.
- Subject must have previously documented chronic hepatitis C genotype 1 infection.
- Subject must have a liver biopsy with histology consistent with chronic hepatitis C infection and no other etiology.
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- Subjects with bridging fibrosis or cirrhosis must have an ultrasound within 6 months 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.
- Subjects must be willing to give written informed consent.
Who cannot join
- Subject will be excluded from entry if ANY of the criteria listed below are
- met:
- Subjects known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) and/or demonstrating signs and symptoms consistent with co-infection.
- Subjects who required discontinuation of previous interferon or ribavirin regimen for an adverse event considered by the investigator to be possibly or probably related to ribavirin and/or interferon.
- Treatment with ribavirin within 90 days and any interferon alfa within 1 month of Screening.
- Treatment for hepatitis C with any investigational medication. Prior treatment with herbal remedies with known hepatotoxicity is exclusionary.
Show all 39Show fewer
- 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.
- Diabetic and/or hypertensive subjects with clinically significant ocular examination findings.
- Pre-existing psychiatric condition(s).
- Clinical diagnosis of substance abuse.
- 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 who are pregnant or nursing. Subjects who intend to become pregnant during the study period. Male subjects with partners who are or who 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 a life-threatening serious adverse event (SAE) during the screening period.
- Subjects with a history of pancreatitis, except for one episode clearly secondary to gallstone.
- Laboratory Exclusion Criteria:
- Hematologic, biochemical, and serologic criteria (growth factors may not be used to achieve study entry requirements):
- Hemoglobin (Hgb) <12 g/dL for females and <13 g/dL for males
- Neutrophils <1500/mm3 (blacks: <1200/mm3)
- Platelets <100,000/mm3
- Direct bilirubin >1.5 x upper limit of normal (ULN) of the laboratory reference range. Total bilirubin >1.6 mg/dL unless the subject has a history of Gilbert's disease. If Gilbert's disease is the proposed etiology, this must be documented in the subject's chart.
- Serum albumin < lower limit of normal (LLN) of laboratory reference range.
- Thyroid-stimulating hormone (TSH) >1.2 x ULN or <0.8 x LLN of laboratory reference range.
- Serum creatinine >ULN of the laboratory reference range.
- Serum glucose:
- For subjects not previously diagnosed with diabetes mellitus:
- >=140 mg/dL (nonfasting) unless hemoglobin A1c subtype (HbA1c) <=7% OR
- >=100 mg/dL (fasting) unless HbA1c <=7%.
- For subjects previously diagnosed with diabetes mellitus: HbA1c >8.5%.
- Prothrombin time/partial thromboplastin time (PT/PTT) values >10% above laboratory reference range.
- Anti-nuclear antibodies (ANA) >1:320.
- Alpha fetoprotein (AFP):
- AFP >100 ng/mL OR
- AFP 50 to 100 ng/mL requires a liver ultrasound and subjects with findings suspicious for HCC are excluded.
About this study
Official title: A Phase 3 Safety and Efficacy Study of Boceprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin
Based on previous experience with peginterferon alfa-2b/ribavirin in combination with boceprevir, the combination with peginterferon alfa-
2a/ribavirin and boceprevir is expected to be safe and well tolerated. Given the wide utilization of both peginterferons and the clear benefit of the
addition of boceprevir to peginterferon alfa-2b/ribavirin, it is important to demonstrate the safety and efficacy of boceprevir in combination with
peginterferon alfa-2a/ribavirin.
- Conditions
- Hepatitis C, Chronic
- Being tested
- Boceprevir, Placebo, Peginterferon alfa-2a, Ribavirin
- 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, using SCH 503034 200-mg capsules, three times a day (TID) orally (PO) for 48 weeks
PlaceboOther
800 mg, using placebo matching SCH 503034 200-mg capsules, three times a day (TID) orally (PO) for 48 weeks
Peginterferon alfa-2aBiological
Also called Pegasys®
Peginterferon alfa-2a, pre-filled syringes, given 180 μg/week subcutaneously (SC) for 48 weeks
RibavirinDrug
Also called SCH 18908
Ribavirin 200-mg capsules, weight-based dosing
- <75 kg, 1000 mg/day orally (PO), divided twice daily (BID)
- >=75 kg, 1200 mg/day PO, divided BID for 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (Control Arm) | Placebo comparator | Peginterferon alfa-2a (180 μg/week subcutaneously [SC]) plus ribavirin (1000 to 1200 mg/day orally [PO]) for 4 weeks followed by placebo (800 mg three times a day [TID] PO, using placebo matching SCH 503034 200-mg capsules) + peginterferon alfa-2a 180 μg/week SC plus ribavirin 1000 to 1200 mg/day PO divided twice daily (BID) for 48 weeks with 24 weeks post-treatment follow-up. Receives: Other: Placebo; Biological: Peginterferon alfa-2a; Drug: Ribavirin |
| Arm 2 (Boceprevir Arm) | Experimental | Peginterferon alfa-2a (180 μg/week subcutaneously [SC]) plus ribavirin (1000 to 1200 mg/day orally [PO]) for 4 weeks followed by boceprevir (800 mg three times a day [TID] PO, using SCH 503034 200-mg capsules) + peginterferon alfa-2a 180 μg/week SC plus ribavirin 1000 to 1200 mg/day PO divided twice daily (BID) for 48 weeks
with 24 weeks post-treatment follow-up. Receives: Drug: Boceprevir; Biological: Peginterferon alfa-2a; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Virologic Response (SVR) Rate in Full Analysis Set (FAS) Population.
SVR rate was the percentage of participants treated with at least one dose of study medication (PEG2a, Ribavirin, or Boceprevir/Placebo) who had achieved SVR. SVR was defined as undetectable Hepatitis C Virus-Ribonucleic Acid (HCV RNA).
Measured: Follow-up Week 24
Secondary outcomes (4)
SVR Rate in the Modified Intent-to-Treat (mITT) Population
SVR rate was the percentage of participants treated with at least one dose of study medication (Boceprevir/PEG2a/Ribavirin or PEG2a/Ribavirin). Participants who discontinued study drugs during the 4-week PEG2a/Ribavirin lead-in period were not included in the mITT population.
Measured: Follow-up Week 24
Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR
EVR was defined as the time to the first undectectable HCV-RNA result at Treatment Week (TW) 2, 4, 8, or 12. Participants with a detectable, but not quantifiable HCV-RNA result at TW 12 may have undergone retesting. Participants with a detectable result on retesting were to be discontinued per the 12-week futility rule. Participants with an undetectable result on retesting were allowed to continue on treatment, and the detectable but not quantifiable result was to be considered a false positive.
Measured: Day 1 to Treatment Week 12
Number of Participants With Undetectable HCV-RNA at Follow-up Week 12
Measured: Follow-up Week 12
Mean Log Change From Baseline to TW 4 in Viral Load by Visit
HCV-RNA levels were quantified using the Roche Cobas Taqman 1.0 assay; lower limit of detection of 15 international units [IU]/mL. Changes in HCV-RNA IU/ml were expressed on a log10 scale.
Measured: From Baseline to TW 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2009 (estimated)
- Study startFeb 2009
- Primary completionOct 2010
- Study completionOct 2010
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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 202 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00845065
- Sponsor's protocol ID
- P05685
- Status last verified
- Mar 2017
- First submitted
- 13 Feb 2009
- Last updated
- 7 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php
Publications
Flamm SL, Lawitz E, Jacobson I, Bourliere M, Hezode C, Vierling JM, Bacon BR, Niederau C, Sherman M, Goteti V, Sings HL, Barnard RO, Howe JA, Pedicone LD, Burroughs MH, Brass CA, Albrecht JK, Poordad F. Boceprevir with peginterferon alfa-2a-ribavirin is effective for previously treated chronic hepatitis C genotype 1 infection. Clin Gastroenterol Hepatol. 2013 Jan;11(1):81-87.e4; quiz e5. doi: 10.1016/j.cgh.2012.10.006. Epub 2012 Oct 10.
PubMed 23064222
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Safety and Efficacy Study of Boceprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Peginterferon/Ribavirin
- ClinicalTrials.gov ID
- NCT00845065
- Acronym / sponsor ID
- P05685
- Conditions
- Hepatitis C, Chronic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 202 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Feb 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 16 Feb 2009 (estimated)
- Results
- Posted 2 Feb 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Based on previous experience with peginterferon alfa-2b/ribavirin in combination with boceprevir, the combination with peginterferon alfa-
2a/ribavirin and boceprevir is expected to be safe and well tolerated. Given the wide utilization of both peginterferons and the clear benefit of the
addition of boceprevir to peginterferon alfa-2b/ribavirin, it is important to demonstrate the safety and efficacy of boceprevir in combination with
peginterferon alfa-2a/ribavirin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (Control Arm) | Placebo comparator | Other: Placebo, Biological: Peginterferon alfa-2a, Drug: RibavirinPeginterferon alfa-2a (180 μg/week subcutaneously [SC]) plus ribavirin (1000 to 1200 mg/day orally [PO]) for 4 weeks followed by placebo (800 mg three times a day [TID] PO, using placebo matching SCH 503034 200-mg capsules) + peginterferon alfa-2a 180 μg/week SC plus ribavirin 1000 to 1200 mg/day PO divided twice daily (BID) for 48 weeks with 24 weeks post-treatment follow-up. |
| Arm 2 (Boceprevir Arm) | Experimental | Drug: Boceprevir, Biological: Peginterferon alfa-2a, Drug: RibavirinPeginterferon alfa-2a (180 μg/week subcutaneously [SC]) plus ribavirin (1000 to 1200 mg/day orally [PO]) for 4 weeks followed by boceprevir (800 mg three times a day [TID] PO, using SCH 503034 200-mg capsules) + peginterferon alfa-2a 180 μg/week SC plus ribavirin 1000 to 1200 mg/day PO divided twice daily (BID) for 48 weeks with 24 weeks post-treatment follow-up. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects must have a qualifying regimen defined as peginterferon alfa-2a/ribavirin or peginterferon alfa-2b/ribavirin for a minimum of 12 weeks.
- During the qualifying regimen, subjects must have either:
- Subject must have previously documented chronic hepatitis C genotype 1 infection.
- Subject must have a liver biopsy with histology consistent with chronic hepatitis C infection and no other etiology.
- Subjects with bridging fibrosis or cirrhosis must have an ultrasound within 6 months with no findings suspicious for hepatocellular carcinoma (HCC).
Key exclusion criteria (39 listed)
- Subject will be excluded from entry if ANY of the criteria listed below are
- Subjects known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) and/or demonstrating signs and symptoms consistent with co-infection.
- Subjects who required discontinuation of previous interferon or ribavirin regimen for an adverse event considered by the investigator to be possibly or probably related to ribavirin and/or interferon.
- Treatment with ribavirin within 90 days and any interferon alfa within 1 month of Screening.
- Treatment for hepatitis C with any investigational medication. Prior treatment with herbal remedies with known hepatotoxicity is exclusionary.
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, using SCH 503034 200-mg capsules, three times a day (TID) orally (PO) for 48 weeks | Drug | Arm 2 (Boceprevir Arm) |
| Placebo800 mg, using placebo matching SCH 503034 200-mg capsules, three times a day (TID) orally (PO) for 48 weeks | Other | Arm 1 (Control Arm) |
| Peginterferon alfa-2aAlso: Pegasys®Peginterferon alfa-2a, pre-filled syringes, given 180 μg/week subcutaneously (SC) for 48 weeks | Biological | Arm 1 (Control Arm), Arm 2 (Boceprevir Arm) |
| RibavirinAlso: SCH 18908Ribavirin 200-mg capsules, weight-based dosing * <75 kg, 1000 mg/day orally (PO), divided twice daily (BID) * >=75 kg, 1200 mg/day PO, divided BID for 48 weeks | Drug | Arm 1 (Control Arm), Arm 2 (Boceprevir Arm) |
Primary outcome
Sustained Virologic Response (SVR) Rate in Full Analysis Set (FAS) Population.
Time frame: Follow-up Week 24
SVR rate was the percentage of participants treated with at least one dose of study medication (PEG2a, Ribavirin, or Boceprevir/Placebo) who had achieved SVR. SVR was defined as undetectable Hepatitis C Virus-Ribonucleic Acid (HCV RNA).
4 secondary outcomes
SVR Rate in the Modified Intent-to-Treat (mITT) Population
Time frame: Follow-up Week 24
Percentage of Participants With Early Virologic Response (EVR) Who Achieved SVR
Time frame: Day 1 to Treatment Week 12
Number of Participants With Undetectable HCV-RNA at Follow-up Week 12
Time frame: Follow-up Week 12
Mean Log Change From Baseline to TW 4 in Viral Load by Visit
Time frame: From Baseline to TW 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23064222Flamm SL, Lawitz E, Jacobson I, Bourliere M, Hezode C, Vierling JM, Bacon BR, Niederau C, Sherman M, Goteti V, Sings HL, Barnard RO, Howe JA, Pedicone LD, Burroughs MH, Brass CA, Albrecht JK, Poordad F. Boceprevir with peginterferon alfa-2a-ribavirin is effective for previously treated chronic hepatitis C genotype 1 infection. Clin Gastroenterol Hepatol. 2013 Jan;11(1):81-87.e4; quiz e5. doi: 10.1016/j.cgh.2012.10.006. Epub 2012 Oct 10.
- Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
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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-2a and Ribavirin 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 11 inclusion and 39 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 7 Apr 2017. 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. Some participants in this study may receive a placebo. 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 2 Feb 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?
Sustained Virologic Response (SVR) Rate in Full Analysis Set (FAS) Population. (time frame: 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 NCT00845065, 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 7 Apr 2017.