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Hepatitis C, ChronicPhase 3SPRINT-2NCT00705432

Safety and Efficacy of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1 (Study P05216AM2) (COMPLETED)

A Phase 3 study testing Peginterferon alfa-2b (PEG), Ribavirin (RBV) and Boceprevir 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
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Trial summary

This study involves treatment with boceprevir or placebo in combination with PegIntron (PEG) + Ribavirin (RBV) (weight-based dosing [WBD]) in previously untreated adult participants with chronic hepatitis C (CHC) genotype 1. 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?
Peginterferon alfa-2b (PEG), Ribavirin (RBV) and Boceprevir
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,472 participants
Where
No sites listed yet
Study dates
Aug 2008to May 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

  • Participant must have previously documented CHC genotype 1 infection.
  • Participant must have a liver biopsy with histology consistent with CHC and no other etiology.
  • Participants 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).
  • Participant must be >=18 years of age.
  • Participant must weigh between 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 drug, or longer if dictated by local regulations.
  • Participants must be willing to give written informed consent.

Who cannot join

  • Coinfection with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive).
  • Participants 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 participants with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality.
Show all 23Show fewer
  • 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 participant'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). Participants under evaluation for malignancy are not eligible.
  • Participants who are pregnant or nursing. Participants who intend to become pregnant during the study period. Male participants 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 participant unsuitable for enrollment or could interfere with the participant participating in and completing the study.
  • Participants who are part of the site personnel directly involved with this study.
  • Participants who are family members of the investigational study staff.
  • Participants 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.

About this study

Official title: A Phase 3, Safety and Efficacy Study of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1

This study involves treatment with boceprevir or placebo in combination with PegIntron (PEG) + Ribavirin (RBV) (weight-based dosing [WBD]) in previously untreated adult participants with chronic hepatitis C (CHC) genotype 1. It is hypothesized that the addition of a third active anti- Hepatitis C Virus (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 sustained virologic response (SVR) and shorter treatment durations (in some populations) than treatment with PegIntron plus ribavirin alone.

The study includes two separate cohorts, Cohort I (White participants) and Cohort II (Black participants). Participants from each cohort are assigned (randomized) to one of three study arms, all of which have a 4-week lead-in period with (PEG + RBV).

Read the detailed description

Participants from Cohort I and Cohort II are assigned (randomized) to one of three study arms, all of which have a 4-week lead-in period with (PEG + RBV).

  1. Control arm, participants are treated with (PEG + RBV + placebo) for 44 weeks after the lead-in.
  2. Experimental arm with Response Guided Therapy (RGT) In this experimental arm, participants are treated with all three drugs (PEG + RBV + boceprevir) for 24 weeks after the lead-in. At treatment week 28, those participants with undetectable Hepatitis C Virus - ribonucleic acid (HCV-RNA) from week 8 (up to treatment week 24), will be considered to complete treatment, and will enter follow-up. Participants with detectable for HCV-RNA at week 8 or later will receive an additional 20 weeks of therapy with PegIntron and Ribavirin (PEG + RBV + placebo).
  3. Experimental arm, participants are treated with all three drugs (PEG + RBV + Ribavirin) for 44 weeks after the lead-in.

All participants were followed up to 72 weeks following randomization.

Being tested
Peginterferon alfa-2b (PEG), Ribavirin (RBV), Placebo, Boceprevir
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.

  • Peginterferon alfa-2b (PEG)Biological

    Also called PegIntron, PEG, SCH 54031

    Peginterferon alfa-2b 1.5 μg/kg/week subcutaneously (SC)

  • Ribavirin (RBV)Drug

    Also called Rebetol, RBV, SCH 18908

    Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day administered orally, divided twice daily (BID).

  • PlaceboDrug

    Placebo to boceprevir, 800 mg (4 x 200mg capsules) administered orally three times a day (TID).

  • BoceprevirDrug

    Also called SCH 503034, Victrelis

    Boceprevir, 800 mg (4 x 200 mg capsules) administered orally TID.

Study groups in NCT00705432
Study groupRoleWhat they receive
1. Placebo + PEG + RBVPlacebo comparatorPegIntron (PEG) 1.5 μg/kg + Ribavirin (RBV) (weight-based dosing [WBD]) for 4 weeks (lead in treatment) followed by placebo + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.
Receives: Biological: Peginterferon alfa-2b (PEG); Drug: Ribavirin (RBV); Drug: Placebo
2. Boceprevir + PEG + RBV - 24 Weeks (RGT)ExperimentalPEG 1.5 μg/kg + RBV (WBD) for 4 weeks (lead in treatment) followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 24 weeks. Participants were offered a response guided therapy (RGT) at treatment week 28. * At the Treatment Week 28 visit, participants whose HCV-RNA was undetectable from Treatment Weeks 8 to Treatment Week 24, will proceed to the 44-week follow-up. * At the Treatment Week 28 visit, participants 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.
Receives: Biological: Peginterferon alfa-2b (PEG); Drug: Ribavirin (RBV); Drug: Boceprevir
3. Boceprevir + PEG + RBV - 44 WeeksExperimentalPEG 1.5 μg/kg + RBV (WBD) for 4 weeks (lead in treatment) followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up.
Receives: Biological: Peginterferon alfa-2b (PEG); Drug: Ribavirin (RBV); Drug: Boceprevir

What is being measured

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

  1. Sustained Virologic Response (SVR) Rate

    Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate is the percent of participants achieving SVR.

    HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.

    If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have SVR.

    Measured: At Follow-up Week (FW) 24

Secondary outcomes (4)

  1. Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo)

    Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate was the percentage of participants treated with at least one dose of boceprevir or placebo who had achieved SVR.

    HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.

    If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have a SVR.

    Measured: At FW 24

  2. Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization.

    Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. The number of participants who had undetectable plasma HCV-RNA at FW 12, and 72 weeks after randomization are reported.

    HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.

    Measured: At FW 12 and at 72 weeks after randomization

  3. Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20)

    Early virologic response was defined as undetectable HCV-RNA at in participants by treatment week 2, 4, 8, 12, 16, or 20.

    HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.

    Measured: At Treatment Week 2, 4, 8, 12, 16, or 20

  4. Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR

    Participants with early virologic response were those who had undetectable HCV-RNA by treatment week 4, 8, 12, 16, or 20. Participants who had undetectable plasma HCV-RNA at FW 24 had SVR. The number of participants with early virologic response that also achieved SVR is reported.

    HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.

    Measured: At Treatment Week 4, 8, 12, 16, 20

Timeline

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

  1. First posted26 Jun 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionMay 2010
  4. Study completionMay 2010

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
1,472 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00705432
Sponsor's protocol ID
P05216
Other IDs
EUDRACT # 2007-005508-42
Acronym
SPRINT-2
Status last verified
Mar 2017
First submitted
24 Jun 2008
Last updated
7 Apr 2017
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

  • Ferrante SA, Chhatwal J, Brass CA, El Khoury AC, Poordad F, Bronowicki JP, Elbasha EH. Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study. BMC Infect Dis. 2013 Apr 27;13:190. doi: 10.1186/1471-2334-13-190.

    PubMed 23621902

  • Poordad F, Bronowicki JP, Gordon SC, Zeuzem S, Jacobson IM, Sulkowski MS, Poynard T, Morgan TR, Molony C, Pedicone LD, Sings HL, Burroughs MH, Sniukiene V, Boparai N, Goteti VS, Brass CA, Albrecht JK, Bacon BR; SPRINT-2 and RESPOND-2 Investigators. Factors that predict response of patients with hepatitis C virus infection to boceprevir. Gastroenterology. 2012 Sep;143(3):608-618.e5. doi: 10.1053/j.gastro.2012.05.011. Epub 2012 May 21.

    PubMed 22626609

  • Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP; SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31;364(13):1195-206. doi: 10.1056/NEJMoa1010494.

    PubMed 21449783

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Peginterferon alfa-2b (PEG), Ribavirin (RBV) and Boceprevir 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 7 inclusion and 23 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 14 Jun 2011). 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 (time frame: At Follow-up Week (FW) 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 NCT00705432, which also lists 3 linked publications.

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.

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