Short Duration Versus Standard Response-Guided Therapy With Boceprevir Combined With PegIntron and Ribavirin in Previously Untreated Non-Cirrhotic Asian Participants With Chronic HCV Genotype 1 (MK-3034-107)

A Phase 3 Clinical Trial to Study Short Duration Versus Standard Response-Guided Therapy With MK-3034 (SCH 503034)/Boceprevir Combined With PegIntron and Ribavirin in Previously Untreated Non-Cirrhotic Subjects With Chronic HCV Genotype 1 in Asia

The purpose of this study is to estimate the difference in the efficacy between a 16-week treatment regimen of boceprevir (BOC) in combination with peg-intron alpha 2b (P) plus ribavirin (R) (BOC + PR) and a 28-week treatment regimen of BOC + PR in previously untreated participants with chronic hepatitis C (CHC) genotype 1 in Asia who achieve undetectable hepatitis C virus ribonucleic acid (HCV RNA).

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Boceprevir; Biological: Peg-interferon alfa-2b; Drug: Ribavirin

• Study Type: Interventional
• Enrollment (Actual): 257
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• weigh ≥ 40 kg and ≤ 125 kg
• have CHC genotype 1 infection
• has had a liver biopsy or non-invasive liver fibrosis test that shows no evidence of cirrhosis and hepatocellular carcinoma
• must agree that the participant and the participant's partner will each 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 medication, or longer if dictated by local regulations (for a female participant who is of childbearing potential or male participant with female sexual partner who is of childbearing potential)

Exclusion Criteria:

• participates in any other interventional clinical trial within 30 days of the screening visit in this trial or intends to participate in another interventional clinical trial during participation in this trial
• is co-infected with human immunodeficiency virus (HIV) or hepatitis B virus
• has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis
• has evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy
• has evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
• has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years
• has been previously treated with an interferon or ribavirin regimen or HCV direct acting anti-viral regimen, or treated for hepatitis C with any investigational medication
• taking/plans to take significant inducers of inhibitors of Cytochrome P450 3A4 (CYP3A4) substrates 2 weeks prior to start of study medications, or herbal supplements, including but not limited to St. John's Wort 2 weeks prior to start of study medications (Day 1)
• has pre-existing psychiatric condition(s)
• has a clinical diagnosis of substance abuse
• has any known medical condition that could interfere with the participation in and completion of the trial including immunologically-mediated disease, chronic pulmonary disease, or current or history of any clinically significant cardiac abnormalities/dysfunction
• is pregnant or nursing (for female participant) or female partner intends to become pregnant (for male participant)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: 16-week Treatment Arm; All screened and enrolled participants initially underwent a 12-week (4 weeks PR + 8 weeks BOC + PR) lead-in treatment period prior to randomization to Arms 1 or 2 (participants with undetectable HCV RNA) or allocation to Arm 3 (participants with detectable HCV RNA). After completing the 12-week lead-in, participants with undetectable HCV RNA were randomized to receive an additional 4 weeks of BOC + PR, for a total of 16 weeks of treatment. At Week 16, participants underwent 12 weeks of follow-up (participation complete at Week 28).	Drug: Boceprevir; 800 mg three times daily orally; Other Names: MK-3034; Biological: Peg-interferon alfa-2b; 1.5 mcg/kg weekly subcutaneously; Other Names: PegIntron; Drug: Ribavirin; 800-1400 mg twice-daily divided orally based on body weight; Other Names: Rebetol
Experimental: Arm 2: 28-week Treatment Arm; All screened and enrolled participants initially underwent a 12-week (4 weeks PR + 8 weeks BOC + PR) lead-in treatment period prior to randomization to Arms 1 or 2 (participants with undetectable HCV RNA) or allocation to Arm 3 (participants with detectable HCV RNA). After completing the 12-week lead-in, participants with undetectable HCV RNA were randomized to receive an additional 16 weeks of BOC + PR, for a total of 28 weeks of treatment. At Week 28, participants underwent 12 weeks of follow-up (participation complete at Week 40).	Drug: Boceprevir; 800 mg three times daily orally; Other Names: MK-3034; Biological: Peg-interferon alfa-2b; 1.5 mcg/kg weekly subcutaneously; Other Names: PegIntron; Drug: Ribavirin; 800-1400 mg twice-daily divided orally based on body weight; Other Names: Rebetol
Experimental: Arm 3: 48-week Treatment Arm; All screened and enrolled participants initially underwent a 12-week (4 weeks PR + 8 weeks BOC + PR) lead-in treatment period prior to randomization to Arms 1 or 2 (participants with undetectable HCV RNA) or allocation to Arm 3 (participants with detectable HCV RNA). After completing the 12-week lead-in, participants with detectable HCV RNA were allocated to receive an additional 24 weeks of BOC + PR and an additional 12 weeks of PR, for a total of 48 weeks of treatment. At Week 48, participants underwent 12 weeks of follow-up (participation complete at Week 60).	Drug: Boceprevir; 800 mg three times daily orally; Other Names: MK-3034; Biological: Peg-interferon alfa-2b; 1.5 mcg/kg weekly subcutaneously; Other Names: PegIntron; Drug: Ribavirin; 800-1400 mg twice-daily divided orally based on body weight; Other Names: Rebetol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Undetectable HCV RNA Who Achieve Sustained Viral Response at Follow-up Week 12 (SVR12) [16-Week Arm vs. 28-Week Arm]	SVR12 was declared when participants who had undetectable HCV RNA (HCV RNA < Lower Limit of Quantification [LLoQ]) after the 12-week lead-in also had undetectable HCV RNA 12 weeks after completing their assigned BOC treatment regimen. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL.	Follow-up Week (FW) 12 (up to 40 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Undetectable HCV RNA Across Treatment	The percentage of participants with undetectable HCV RNA (HCV RNA <LLoQ) at TW4, TW8, and TW12 is summarized for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL.	TW4, TW8, and TW12
Percentage of Participants Achieving SVR12 Among Participants With Undetectable HCV RNA Across Treatment	The percentage of participants achieving SVR12 who had undetectable HCV RNA (HCV RNA <LLoQ) at Week 4, Week 8, and Week 12 is summarized for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL.	TW4, TW8, and TW12
Percentage of Participants With Relapse	The percentage of viral relapse (defined as confirmed HCV RNA >15 IU/mL after End-of-Treatment [EOT]) among participants who had undetectable HCV RNA at EOT was determined for each arm. The Roche COBAS™ Taqman™ automated HCV test (v2.0 assay) used in this study has a LLoQ of 15 IU/mL.	From EOT to FW12 (up to 12 weeks)
Percentage of Participants With Neutropenia	The percentage of participants with neutropenia (neutrophil count <0.75 x10^9/L) is summarized for each arm.	Up to 60 weeks
Percentage of Participants With Anemia	The percentage of participants with anemia (hemoglobin [Hgb] <10 g/dL) was determined in each arm.	Up to 60 weeks
Percentage of Participants With Dose Discontinuation Due to Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The percentage of participants who discontinued from BOC, BOC + RBV, or all medications due to an AE are reported.	From TW1 through TW48
Percentage of Participants With Treatment-Related Serious AEs (SAEs)	A SAE is any AE that results in death, is life threatening, results in persistent or significant disability, results in or prolongs an existing inpatient hospitalization, is a congenital birth defect, is a cancer, is associated with an overdose, or is another important medical event.	Up to 60 weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2013
• Primary Completion (Actual): August 5, 2015
• Study Completion (Actual): November 4, 2015

Study Registration Dates

• First Submitted: September 13, 2013
• First Submitted That Met QC Criteria: September 13, 2013
• First Posted (Estimate): September 18, 2013

Study Record Updates

• Last Update Posted (Actual): July 12, 2018
• Last Update Submitted That Met QC Criteria: June 14, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Ribavirin; Interferon alpha-2; Peginterferon alfa-2b
• Other Study ID Numbers: 3034-107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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