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peginterferon alfa 2b

Phase 3

Hepatitis C, Chronic | Monoclonal antibody | Infectious Disease |Merck & Company, Inc.|Last Updated: Apr 7, 2017

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials6
Total Enrollment2,582
FDA Designations
No designations recorded
Clinical Trials (6)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00705432Safety and Efficacy of Boceprevir in Previously Untreated Subjects With Chronic Hepatitis C Genotype 1 (Study P05216AM2) (COMPLETED)PHASE3 COMPLETED 1,472Aug 1, 2008May 1, 2010Apr 7, 2017 -
NCT007617355 Year Long-term Follow up in Pediatric Participants Who Received PegIntron Plus Rebetol in P02538 Part I (P02538 Pt 2)PHASE3 COMPLETED 94Jul 1, 2007Jan 1, 2013Apr 4, 2017 -
NCT00687219Efficacy and Safety of Peginterferon Alfa-2b and Ribavirin Therapy in Subjects With Type C Compensated Liver Cirrhosis (Study P05116)PHASE3 COMPLETED 102Jun 1, 2007Oct 1, 2010Apr 7, 2017 -
NCT00104052Study of PEG-Intron Plus REBETOL in Pediatric Subjects With Chronic Hepatitis C (Study P02538 Part 1)PHASE3 COMPLETED 107Feb 1, 2005Nov 1, 2007Apr 4, 2017 -
NCT00302081Three Regimens of PegIntron Plus Ribavirin in Previously Untreated Chronic Hepatitis C, Genotype 2 or 3 (Study P03548)PHASE3 COMPLETED 696Aug 1, 2003Apr 1, 2008Apr 5, 2017 -
NCT00797745A Pharmacokinetics/Pharmacodynamics Study of SCH 900518 in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C (Protocol No. P05104AM2)(COMPLETED)PHASE2 COMPLETED 111Nov 1, 2008Sep 1, 2010Jan 22, 2015 -
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Study Endpoints
Primary Endpoints
Sustained Virologic Response (SVR) Rate
At Follow-up Week (FW) 24

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.

Number of Participants Who Relapsed At End of LTFU Year 5
Part 2 LTFU Year 5

Relapse was defined as Hepatitis C Virus ribonucleic acid (HCV-RNA) that was above the lower limit of quantitation at Year 5 of the LTFU.

Mean Height Percentiles of Participants Over LTFU
Part 1 Pre-treatment Baseline, Part 2 LTFU Year 1, Part 2 LTFU Year 2, Part 2 LTFU Year 3, Part 2 LTFU Year 4, Part 2 LTFU Year 5, Last Available LTFU Visit (up to 5 years)

To determine long-term effects of the Part 1 treatment on height, changes in height during the Part 2 LTFU were evaluated using height percentiles based on 2000 Center For Disease Control growth charts for the general population.

Mean Weight Percentiles of Participants Over LTFU
Part 1 Pre-treatment Baseline, Part 2 LTFU Year 1, Part 2 LTFU Year 2, Part 2 LTFU Year 3, Part 2 LTFU Year 4, Part 2 LTFU Year 5, Last Available LTFU Visit (up to 5 years)

To determine long-term effects of the Part 1 treatment on weight, changes in weight during the Part 2 LTFU were evaluated using weight percentiles based on 2000 Center For Disease Control growth charts for the general population.

Mean Body Mass Index (BMI) Percentiles of Participants Over LTFU
Part 1 Pre-treatment Baseline, Part 2 LTFU Year 1, Part 2 LTFU Year 2, Part 2 LTFU Year 3, Part 2 LTFU Year 4, Part 2 LTFU Year 5, Last Available LTFU Visit (up to 5 years)

To determine long-term effects of the Part 1 treatment on BMI, changes in BMI during the Part 2 LTFU were evaluated using BMI percentiles based on 2000 Center For Disease Control growth charts for the general population.

Mean Age at Attained Tanner Stages (Sexual Maturity) at End of LTFU (Last Observation) By Gender
Last assessment of the Part 2 LTFU (up to 5 years)

The Tanner Stage (TS) defines physical measurements of sexual development based on external primary and secondary sex characteristics. Female participants are evaluated for breast development and pubic hair distribution and male participants are evaluated for genital development and pubic hair distribution, based on a 5-stage ordinal scale ranging from TS 1 (prepubertal/preadolescent characteristics) to TS 5 (mature or adult characteristics). Mean ages for attaining each TS in the normal population have been previously established based on measuring correlating reproductive hormone levels, and are expressed in years as follows for females (F) and males (M): TS 1= 7.1 (F+M); TS 2= 10.5 (F), 12.1 (M); TS 3= 11.6 (F), 13.6 (M); TS 4=, 12.3 (F), 15.1 (M); TS 5= 14.5 (F), 18 (M). To assess sexual maturation at the end of the LTFU (last observation), females and males were staged and the mean age at each TS attained was reported.

Number of Participants With Undetectable HCV-RNA at Week 72 (Sustained Virologic Response)
Measured at 24 weeks after 48 weeks treatment (72 weeks)

Serum HCV-RNA was qualitatively measured by reverse transcriptase polymerase chain reaction (RT-PCR)

Number of Participants With a Sustained Virologic Response (SVR) at 24 Weeks Post-treatment
Up to 48-week treatment duration. Follow-up of 24 weeks.

SVR is defined as undetectable hepatitis C virus ribonucleic acid (HCV-RNA) at 24 weeks post-treatment

The Number of Participants Who Achieve a Sustained Virologic Response (SVR)
24-week treatment duration for Arms [Peg2b 1.5/R(24 weeks)] and [PEG2b 1.0/R(24 weeks]); 16-week treatment duration for Arm [PEG2b 1.5/R(16 weeks]. Follow-up of 24 weeks for each arm.

A sustained virologic response is defined as undetectable hepatitis C virus ribonucleic acid \[HCV-RNA\] 24 weeks post-treatment. Serum HCV-RNA is measured by HCV-PCR in local laboratories. HCV-RNA below the limit of detection is considered undetectable.

The primary efficacy endpoint is the proportion of subjects with undetectable HCV-RNA after 4 weeks of treatment with SCH 900518.
After 4 weeks of treatment with SCH 900518
Secondary Endpoints
Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo)
At FW 24
Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization.
At FW 12 and at 72 weeks after randomization
Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20)
At Treatment Week 2, 4, 8, 12, 16, or 20
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
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.
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.
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.
PEG-IFN + RBV: LTFUOTHERPediatric participants who completed treatment with peginterferon alfa-2b (PEG-IFN) plus ribavirin (RBV) in P02538 Part 1 of this study (NCT00104052) were enrolled in a 5-year Long Term Follow-Up (LTFU) during P02538 Part 2 (NCT00761735). No study treatment was administered in Part 2.
Peginterferon alfa-2b + RibavirinEXPERIMENTAL -
PEG-Intron alfa 2b (PEG2b) plus REBETOL (RBV)EXPERIMENTALPEG2b 1.5 μg/kg/wk given subcutaneously (once weekly) and RBV 400-1200 mg/day by mouth divided in 2 daily doses (administered twice daily with food, dosed 12 hours apart) for 48 weeks. Subjects treated up to 48 weeks and followed for additional 24 weeks after the end of treatment (total of 72 weeks study participation).
PEG2b 1.5/R (24 weeks)ACTIVE_COMPARATORPegIntron (peginterferon alfa-2b; SCH 54031) 1.5 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg daily for 24 weeks
PEG 2b 1.0/R (24 weeks)EXPERIMENTALPegIntron (peginterferon alfa-2b; SCH 54031) 1.0 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg/day for 24 weeks
PEG2b 1.5/R (16 weeks)EXPERIMENTALPegIntron (peginterferon alfa-2b; SCH 54031) 1.5 mcg/kg QW SC plus ribavirin (SCH 18908) 800-1200 mg/day for 16 weeks
Standard of CareACTIVE_COMPARATORPegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily for 48 weeks. * Subjects with \>= 1 log decrease from baseline in HCV-RNA levels after 12 weeks, but still above the lower limit of quantitation, have the option of crossing over to PegIntron, ribavirin plus SCH 900518 400 mg and ritonavir 100 mg daily for 12 weeks. This is followed by standard of care, PegIntron and ribavirin, for a total treatment duration of up to 48 weeks.
2EXPERIMENTALPegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily plus SCH 900518 200 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 12 or 36 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.
3EXPERIMENTALPegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily plus SCH 900518 400 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 12 or 36 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.
4EXPERIMENTAL4 week lead-in with PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily followed by PegIntron plus ribavirin plus SCH 900518 200 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 8 or 32 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.
5EXPERIMENTAL4 week lead-in with PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily followed by PegIntron plus ribavirin plus SCH 900518 400 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 8 or 32 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.
6EXPERIMENTALPegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily plus SCH 900518 100 mg twice daily plus ritonavir 100 mg twice daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 12 or 36 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.
7EXPERIMENTAL4 week lead-in with PegIntron 1.5 mcg/kg SC weekly plus ribavirin 600 to 1400 mg daily (weight-based) by mouth twice daily followed by PegIntron plus ribavirin plus SCH 900518 600 mg daily plus ritonavir 100 mg daily for 12 weeks. Depending on HCV-RNA levels after 4 weeks of SCH 900518, patients will receive an additional 8 or 32 weeks of PegIntron/ribavirin. Total treatment duration will be 24 or 48 weeks.
Interventions
NameTypeDescription
Peginterferon alfa-2b (PEG)BIOLOGICALPeginterferon alfa-2b 1.5 μg/kg/week subcutaneously (SC)
Ribavirin (RBV)DRUGRibavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day administered orally, divided twice daily (BID).
PlaceboDRUGPlacebo to boceprevir, 800 mg (4 x 200mg capsules) administered orally three times a day (TID).
BoceprevirDRUGBoceprevir, 800 mg (4 x 200 mg capsules) administered orally TID.
Peginterferon alfa-2bBIOLOGICALIn the previous treatment protocol (P02538 Part 1), peginterferon alfa-2b was administered at a dose of 60 μg/m\^2 by subcutaneous injection weekly for up to 48 weeks. No treatment was administered on the current follow-up study (P02538 Part 2).
RibavirinDRUGIn the previous treatment protocol (P02538 Part 1), ribavirin was administered at a dose of 15 mg/kg/day orally in two divided doses for up to 48 weeks. No treatment was administered on the current follow-up study (P02538 Part 2).
peginterferon alfa-2b (PEG2b) (SCH 54031)BIOLOGICALPEG2b 1.5 μg/kg/wk given subcutaneously (once weekly) for 48 weeks.
ribavirin (SCH 18908)DRUG15 mg/kg/day for up to 48 weeks
peginterferon alfa-2b (SCH 54031)BIOLOGICAL1.5 mcg/kg QW SC for 24 weeks
peginterferon alfa 2bBIOLOGICAL1.5 mcg/kg subcutaneously weekly for up to 24 or 48 weeks
SCH 900518DRUGSCH 900518 100 mg tablets taken as 200 mg PO QD, 100 mg PO BID, 400 mg PO QD, or 600 mg PO QD for 12 weeks.
ritonavirDRUGRitonavir 100 mg capsules taken as 100 mg PO QD or 100 mg PO BID for 12 weeks.
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo

Inclusion Criteria: * 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 Vi...

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