NCT00160251

Brief Summary

The primary objective of this study is to determine the safe and effective dose range of boceprevir (SCH 503034) in combination with PEG-Intron in adult subjects who have chronic hepatitis C without cirrhosis, and who have failed an adequate course of combination therapy with peginterferon-alfa plus ribavirin. A secondary objective is to explore whether ribavirin provides an additional benefit when combined with PEG-Intron plus boceprevir.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
357

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2005

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2005

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

September 8, 2005

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 12, 2005

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2007

Completed
4.5 years until next milestone

Results Posted

Study results publicly available

December 29, 2011

Completed
Last Updated

October 14, 2015

Status Verified

October 1, 2015

Enrollment Period

1.8 years

First QC Date

September 8, 2005

Results QC Date

May 13, 2011

Last Update Submit

October 13, 2015

Conditions

Keywords

PEG-IntronRibavirinProtease Inhibitor

Outcome Measures

Primary Outcomes (2)

  • Percent of Participants Who Were Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Negative at the End of Treatment (EoT)

    Sustained Viral Response (SVR) was defined as the percentage of participants with HCV-RNA undetectable at the follow-up Week 24. All percentages were based on the total number of participants originally randomized/enrolled to that particular arm. For Arm 1B, the denominator for the percentages was the number who received at least 1 dose of BOC. Arm 1A was not analyzed.

    Baseline up to Week 49

  • Percent of Participants Who Achieved Sustained Virologic Response (SVR)

    SVR was defined as the percentage of participants with Hepatitis C Virus Ribonucleic Acid (HCV-RNA) undetectable at the follow-up Week 24. All percentages were based on the total number of participants originally randomized/enrolled to that particular arm. For Arm 1B, the denominator for the percentages was the number who received at least 1 dose of BOC. Arm 1A was not analyzed.

    Baseline up to Week 73 [24 weeks after end of treatment (EoT)]

Secondary Outcomes (10)

  • Percent of Participants Who Achieved Sustained Viral Response (SVR) by Time to First Negative HCV-RNA

    Baseline up to Week 73 [24 weeks after EoT]

  • Percentage of Participants Who Were HCV-RNA Negative at EoT After Receiving 1 Week of Treatment With PegIntron (PEG) by Log Drop

    Week 1 and Week 49

  • Percent of Participants With Virologic Response Prior to Amendment 2

    Week 3, Week 5, Week 13

  • Peak Plasma Concentration of Boceprevir (BOC)

    All visits during treatment (baseline to Week 49) except Day 1 of Week 1

  • Area Under the Plasma Concentration-time Curve of Boceprevir Plasma Concentration for an 8-hour Dosing Period

    All visits during treatment (baseline to Week 49) except Day 1 of Week 1

  • +5 more secondary outcomes

Study Arms (9)

Arm 1A: PegIntron (PEG) + Ribavirin (RBV)

ACTIVE COMPARATOR

A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is undetected, PEG + RBV will continue for another 36 weeks.

Biological: PegIntron (PEG)Drug: Ribavirin (RBV)

Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400

ACTIVE COMPARATOR

A single dose of PEG is given first, followed 1 week later by PEG + RBV for 12 weeks. If HCV-RNA is detectable, BOC 400 mg TID will be added for 36 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.

Drug: Boceprevir (BOC)Biological: PegIntron (PEG)Drug: Ribavirin (RBV)

Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks)

EXPERIMENTAL

A single dose of PEG is given first, followed 1 week later by PEB + BOC 100 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.

Drug: Boceprevir (BOC)Biological: PegIntron (PEG)

Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks)

EXPERIMENTAL

A single dose of PEG is given first, followed 1 week later by PEG + BOC 200 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.

Drug: Boceprevir (BOC)Biological: PegIntron (PEG)

Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks)

EXPERIMENTAL

A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.

Drug: Boceprevir (BOC)Biological: PegIntron (PEG)

Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400

EXPERIMENTAL

A single dose of PEG is given first, followed 1 week later by PEG + RBV + BOC 400 for 48 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.

Drug: Boceprevir (BOC)Biological: PegIntron (PEG)Drug: Ribavirin (RBV)

Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks)

EXPERIMENTAL

A single dose of PEG is given first, followed 1 week later by PEG + BOC 400 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.

Drug: Boceprevir (BOC)Biological: PegIntron (PEG)

Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800

EXPERIMENTAL

By first protocol amendment to P03659, this non-randomized arm is added. A single dose of PEG is given first, followed 1 week later by PEG + BOC 800 for 24 weeks. By second protocol amendment to P03659, participants will be rolled over into Arm 8 for the remainder of the treatment period.

Drug: Boceprevir (BOC)Biological: PegIntron (PEG)

Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800

EXPERIMENTAL

By second protocol amendment to P03659, participants from all arms except Arm 1A will be rolled over into PEG + RBV + BOC 800 for the remainder of the treatment period.

Drug: Boceprevir (BOC)Biological: PegIntron (PEG)Drug: Ribavirin (RBV)

Interventions

100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID

Also known as: SCH 503034
Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks)Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks)Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks)Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks)Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800
PegIntron (PEG)BIOLOGICAL

1.5 mcg/kg weekly subcutaneously

Arm 1A: PegIntron (PEG) + Ribavirin (RBV)Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks)Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks)Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks)Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks)Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800

200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight \[weight-based dosing {WBD}\])

Arm 1A: PegIntron (PEG) + Ribavirin (RBV)Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Documented infection with chronic hepatitis C (CHC), genotype 1.
  • Documented failure to respond to an adequate course of treatment (minimum 12 weeks) with peginterferon-alfa plus ribavirin (failure defined as \<2 log drop in HCV-RNA after 12 weeks of therapy or those who never become Hepatitis C Virus Ribonucleic Acid (HCV)-RNA negative)
  • No evidence of cirrhosis on liver biopsy.
  • Results of physical examination and laboratory tests within specified ranges.
  • Abstinence from use of abused substances.

You may not qualify if:

  • Women who are pregnant or nursing a child.
  • Patients with cirrhosis, co-infection with Hepatitis B or human immunodeficiency virus (HIV), and African-American patients (by protocol amendment 2, African-American patients can enroll).
  • Previous treatment with any Hepatitis C Virus (HCV) polymerase or protease inhibitor.
  • Patients who relapsed following response to previous treatment.
  • Evidence of advanced liver disease, or liver disease from a cause other than CHC.
  • Pre-existing psychiatric condition.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

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-carboxamidepeginterferon alfa-2bRibavirin

Condition Hierarchy (Ancestors)

Hepatitis CBlood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The implementation of amendment 2 led to changes in boceprevir dose in all treatment arms and different overall lengths of therapy within the same treatment arm, making the SVR endpoint uninterpretable.

Results Point of Contact

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

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 8, 2005

First Posted

September 12, 2005

Study Start

September 1, 2005

Primary Completion

July 1, 2007

Study Completion

July 1, 2007

Last Updated

October 14, 2015

Results First Posted

December 29, 2011

Record last verified: 2015-10