Boceprevir (SCH 503034) Plus Peg-Intron, With and Without Added Ribavirin, in Patients With Chronic Hepatitis C, Genotype 1, Who Did Not Respond to Previous Treatment With Peginterferon Alfa Plus Ribavirin (Study P03659AM2)(COMPLETED) - Full Text View

Sponsor:	Schering-Plough
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00160251

Purpose

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.

Condition	Intervention	Phase
Chronic Hepatitis C	Drug: Boceprevir (BOC) Biological: PegIntron (PEG) Drug: Ribavirin (RBV)	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	PEG-Intron/REBETOL vs PEG-Intron/ SCH 503034 With and Without Ribavirin in Chronic Hepatitis C Virus Genotype 1 (HCV-1) Peginterferon Alfa/Ribavirin Nonresponders: A SCH 503034 Dose-Finding Phase 2 Study

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Interferon alfa-2b Peginterferon Alfa-2b Boceprevir

U.S. FDA Resources

Further study details as provided by Schering-Plough:

Primary Outcome Measures:

Percent of Participants Who Were Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Negative at the End of Treatment (EoT) [ Time Frame: Baseline up to Week 49 ] [ Designated as safety issue: No ]
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.
Percent of Participants Who Achieved Sustained Virologic Response (SVR) [ Time Frame: Baseline up to Week 73 [24 weeks after end of treatment (EoT)] ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Percent of Participants Who Achieved Sustained Viral Response (SVR) by Time to First Negative HCV-RNA [ Time Frame: Baseline up to Week 73 [24 weeks after EoT] ] [ Designated as safety issue: No ]
Percentage of participants who became HCV-RNA undetectable within the first 13 weeks and subsequently became HCV-RNA positive were not considered negative for this analysis.
Percentage of Participants Who Were HCV-RNA Negative at EoT After Receiving 1 Week of Treatment With PegIntron (PEG) by Log Drop [ Time Frame: Week 1 and Week 49 ] [ Designated as safety issue: No ]
For each log drop category (<0, 0 to 0.5, 0.5 to <1, 1 to <1.5, ≥1.5, and Missing), the percentage of participants receiving combination therapy who were HCV-RNA negative at EoT (Week 49) was calculated as follows:

Number of participants in a log category who were HCV-RNA negative divided by the total number of participants in that log drop category (n).

Percentages were NOT derived using treatment arm N values. The sum of the n values for all 6 log drop categories within a treatment arm equals the overall N for that treatment group.
Percent of Participants With Virologic Response Prior to Amendment 2 [ Time Frame: Week 3, Week 5, Week 13 ] [ Designated as safety issue: No ]
Virologic response was defined as the percentage of participants with Hepatitis C Virus Ribonucleic Acid (HCV-RNA) ≤10,000 IU/mL.
Peak Plasma Concentration of Boceprevir (BOC) [ Time Frame: All visits during treatment (baseline to Week 49) except Day 1 of Week 1 ] [ Designated as safety issue: No ]
All plasma samples were assayed using a validated liquid chromatography with tandem mass spectrometric detection (LCMS/MS) method.
Area Under the Plasma Concentration-time Curve of Boceprevir Plasma Concentration for an 8-hour Dosing Period [ Time Frame: All visits during treatment (baseline to Week 49) except Day 1 of Week 1 ] [ Designated as safety issue: No ]
All plasma samples were assayed using a validated liquid chromatography with tandem mass spectrometric detection (LCMS/MS) method.

The dosing interval of 8 hours is represented as the hr in the unit of measure.
Trough Plasma Concentration Level [ Time Frame: All visits during treatment (baseline to Week 49) except Day 1 of Week 1 ] [ Designated as safety issue: No ]
All plasma samples were assayed using a validated liquid chromatography with tandem mass spectrometric detection (LCMS/MS) method.
Change in Alanine Aminotransferase (ALT) Levels [ Time Frame: Baseline up to dosing change (> 25 weeks) ] [ Designated as safety issue: Yes ]
Change in ALT levels during initial treatment regimen and after rolling into amendment 2 as compared to baseline.
Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on Arms 2 (PEG+BOC 100), 3 (PEG+BOC 200), 4 (PEG+BOC 400 [48 Weeks]), 6 (PEG+BOC 400 [24 Weeks]) [ Time Frame: From dosing change to end of follow-up (Week 73)(up to 48 weeks) ] [ Designated as safety issue: No ]
Log drop at baseline of dosing change = difference of log viral loads between baseline (closest to the treatment begin date) and dosing change baseline (virology value closest to the dosing change begin date).
Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Rebetol (RVB) + Boceprevir (BOC) 400 (Arm 5) [ Time Frame: From dosing change to end of follow-up (Week 73)(up to 48 weeks) ] [ Designated as safety issue: No ]
Log drop at baseline of dosing change = difference of log viral loads between baseline (closest to the treatment begin date) and dosing change baseline (virology value closest to the dosing change begin date).
Number of Participants Who Were HCV-RNA Negative During Amendment 2 (AM2) for Those Who Started on PegIntron (PEG) + Boceprevir (BOC) 800 (Arm 7) [ Time Frame: From dosing change to end of follow-up (Week 73) (up to 48 weeks) ] [ Designated as safety issue: No ]
Log drop at baseline of dosing change = difference of log viral loads between baseline (closest to the treatment begin date) and dosing change baseline (virology value closest to the dosing change begin date).

Enrollment:	357
Study Start Date:	September 2005
Study Completion Date:	July 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm 1A: PegIntron (PEG) + Ribavirin (RBV) 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) 1.5 mcg/kg weekly subcutaneously Drug: Ribavirin (RBV) 200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight [weight-based dosing {WBD}])
Active Comparator: Arm 1B: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400 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) 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID Other Name: SCH 503034 Biological: PegIntron (PEG) 1.5 mcg/kg weekly subcutaneously Drug: Ribavirin (RBV) 200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight [weight-based dosing {WBD}])
Experimental: Arm 2: PegIntron (PEG) + Boceprevir (BOC) 100 (48 weeks) 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) 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID Other Name: SCH 503034 Biological: PegIntron (PEG) 1.5 mcg/kg weekly subcutaneously
Experimental: Arm 3: PegIntron (PEG) + Boceprevir (BOC) 200 (48 Weeks) 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) 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID Other Name: SCH 503034 Biological: PegIntron (PEG) 1.5 mcg/kg weekly subcutaneously
Experimental: Arm 4: PegIntron (PEG) + Boceprevir (BOC) 400 (48 weeks) 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) 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID Other Name: SCH 503034 Biological: PegIntron (PEG) 1.5 mcg/kg weekly subcutaneously
Experimental: Arm 5: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 400 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) 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID Other Name: SCH 503034 Biological: PegIntron (PEG) 1.5 mcg/kg weekly subcutaneously Drug: Ribavirin (RBV) 200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight [weight-based dosing {WBD}])
Experimental: Arm 6: PegIntron (PEG) + Boceprevir (BOC) 400 (24 Weeks) 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) 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID Other Name: SCH 503034 Biological: PegIntron (PEG) 1.5 mcg/kg weekly subcutaneously
Experimental: Arm 7: PegIntron (PEG) + Boceprevir (BOC) 800 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) 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID Other Name: SCH 503034 Biological: PegIntron (PEG) 1.5 mcg/kg weekly subcutaneously
Experimental: Arm 8: PegIntron (PEG)+Ribavirin (RBV)+Boceprevir (BOC) 800 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) 100 or 200 mg capusles taken orally as 100 mg, 200 mg, 400 mg, or 800 mg TID Other Name: SCH 503034 Biological: PegIntron (PEG) 1.5 mcg/kg weekly subcutaneously Drug: Ribavirin (RBV) 200 mg capsules taken twice daily (BID) (total daily dose of 800-1400 mg/day, depending on weight [weight-based dosing {WBD}])

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Key inclusion criteria:

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.

Key exclusion criteria:

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Vice President, Late Stage Development Group Leader, Schering-Plough
ClinicalTrials.gov Identifier:	NCT00160251 History of Changes
Other Study ID Numbers:	P03659
Study First Received:	September 8, 2005
Results First Received:	May 13, 2011
Last Updated:	November 23, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Schering-Plough:

PEG-Intron
Ribavirin
Protease Inhibitor

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections

RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2b
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012