Grazoprevir (MK-5172) With Peg-Interferon and Ribavirin in Participants With Chronic Genotype 2 or 3 Hepatitis C (MK-5172-012)
Primary Purpose
Hepatitis C, Chronic
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Grazoprevir
Placebo to Grazoprevir
Peginterferon alfa-2b (Peg-IFN)
Ribavirin (RBV)
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic
Eligibility Criteria
Inclusion Criteria:
- Body weight ≥ 88 lbs and ≤ 275 lbs
- Documented chronic Hepatitis C (CHC) GT2 or GT3 infection
- No known cirrhosis
- Agrees to use two acceptable methods of birth control during study and through 6 months after last dose of study drug
- Chest X-ray within the last 6 months
- Eye exam within the last 6 months
Exclusion Criteria:
- Known to be human immunodeficiency virus (HIV) positive or co-infected with active hepatitis B virus (positive for Hepatitis B surface antigen)
- Prior approved or investigational treatment for hepatitis C
- Evidence of hepatocellular carcinoma
- Diabetic and/or high blood pressure with clinically significant eye exam findings
- Pre-existing psychiatric condition
- Clinical diagnosis of abuse of certain substances within specified timeframes
- Known medical condition that could interfere with participation
- Active or suspected cancer within the last 5 years
- Female who is pregnant, breastfeeding, or expecting to conceive or donate eggs
- Male who is planning to impregnate partner or donate sperm
- Male with a pregnant female partner
- Chronic hepatitis not caused by HCV
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Arm Label
Grazoprevir 200 mg + Peg-IFN + RBV
Grazoprevir 400 mg + Peg-IFN + RBV
Placebo + Peg-IFN + RBV
Grazoprevir 800 mg + Peg-IFN + RBV
Arm Description
Grazoprevir 200 mg in combination with Peg-IFN and RBV for 12 weeks.
Grazoprevir 400 mg in combination with Peg-IFN and RBV for 12 weeks.
Placebo to grazoprevir in combination with Peg-IFN and RBV for 12 weeks, followed by open-label Peg-IFN and RBV for an additional 12 weeks.
Grazoprevir 800 mg in combination with Peg-IFN and RBV for 12 weeks.
Outcomes
Primary Outcome Measures
Number of Participants Achieving Complete Early Virologic Response (cEVR) in the Grazoprevir Treatment Arms
cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v.2.0 assay.
Secondary Outcome Measures
Time to First Achievement of Undetectable HCV Ribonucleic Acid (RNA)
Time to first achievement of undetectable HCV RNA was determined by measuring HCV RNA at Treatment Days 1, 3, and 7; Treatment Weeks 2, 4, 8, 12, 16, 20, and 24; as well as Follow-up Weeks 4, 12, and 24. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Number of Participants Achieving Rapid Viral Response (RVR)
RVR was defined as undetectable HCV RNA at Week 4. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Number of Participants Achieving Sustained Viral Response 12 Weeks After Completion of Therapy (SVR12)
SVR12 was defined as undetectable HCV RNA 12 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Number of Participants Achieving Sustained Viral Response 24 Weeks After Completion of Therapy (SVR24)
SVR24 was defined as undetectable HCV RNA 24 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Number of Participants Achieving Undetectable HCV RNA at Week 12 in the Placebo Arm
HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Number of Participants Achieving Complete Early Virologic Response (cEVR) at Week 24 in the Placebo Arm
cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 24 (i.e., after 12 weeks of placebo + 12 weeks of grazoprevir treatment). HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Full Information
NCT ID
NCT01440595
First Posted
September 22, 2011
Last Updated
August 16, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01440595
Brief Title
Grazoprevir (MK-5172) With Peg-Interferon and Ribavirin in Participants With Chronic Genotype 2 or 3 Hepatitis C (MK-5172-012)
Official Title
A Randomized, Partially Double-Blind, Active-Controlled, Dose-Ranging Estimation Study to Evaluate the Safety, Tolerability, and Efficacy of Different Regimens of MK-5172 When Administered Concomitantly With Pegylated-Interferon and Ribavirin in Treatment-Naive Patients With Chronic Genotype 2 or 3 Hepatitis C Virus Infection
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Terminated
Why Stopped
Preliminary results of MK-5172 PN003 (NCT01353911) suggested a possible dose relationship to elevated transaminase levels in treatment with grazoprevir.
Study Start Date
November 28, 2011 (Actual)
Primary Completion Date
May 1, 2012 (Actual)
Study Completion Date
May 1, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the safety, tolerability, and antiviral activity of grazoprevir (MK-5172) when administered concomitantly with peg-interferon alfa-2b (Peg-IFN) and ribavirin (RBV) to treatment-naïve participants with chronic genotype 2 (GT2) or genotype 3 (GT3) hepatitis C virus (HCV) infections.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Grazoprevir 200 mg + Peg-IFN + RBV
Arm Type
Experimental
Arm Description
Grazoprevir 200 mg in combination with Peg-IFN and RBV for 12 weeks.
Arm Title
Grazoprevir 400 mg + Peg-IFN + RBV
Arm Type
Experimental
Arm Description
Grazoprevir 400 mg in combination with Peg-IFN and RBV for 12 weeks.
Arm Title
Placebo + Peg-IFN + RBV
Arm Type
Placebo Comparator
Arm Description
Placebo to grazoprevir in combination with Peg-IFN and RBV for 12 weeks, followed by open-label Peg-IFN and RBV for an additional 12 weeks.
Arm Title
Grazoprevir 800 mg + Peg-IFN + RBV
Arm Type
Experimental
Arm Description
Grazoprevir 800 mg in combination with Peg-IFN and RBV for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Grazoprevir
Other Intervention Name(s)
MK-5172
Intervention Description
Grazoprevir 100 mg tablets once daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo to Grazoprevir
Intervention Description
Placebo to Grazoprevir once daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Peginterferon alfa-2b (Peg-IFN)
Other Intervention Name(s)
PegIntron®, SCH 054031
Intervention Description
Peg-IFN weekly subcutaneous injection at 1.5 mcg/kg/week for 12 or 24 weeks
Intervention Type
Drug
Intervention Name(s)
Ribavirin (RBV)
Other Intervention Name(s)
Rebetol®, SCH 018908
Intervention Description
Ribavirin 200 mg capsules twice daily at a dose of 600 mg to 1400 mg based on weight for 12 or 24 weeks
Primary Outcome Measure Information:
Title
Number of Participants Achieving Complete Early Virologic Response (cEVR) in the Grazoprevir Treatment Arms
Description
cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v.2.0 assay.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Time to First Achievement of Undetectable HCV Ribonucleic Acid (RNA)
Description
Time to first achievement of undetectable HCV RNA was determined by measuring HCV RNA at Treatment Days 1, 3, and 7; Treatment Weeks 2, 4, 8, 12, 16, 20, and 24; as well as Follow-up Weeks 4, 12, and 24. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time Frame
Baseline to Week 12 for Grazoprevir treatment arms, Week 24 for Placebo arm
Title
Number of Participants Achieving Rapid Viral Response (RVR)
Description
RVR was defined as undetectable HCV RNA at Week 4. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time Frame
Week 4
Title
Number of Participants Achieving Sustained Viral Response 12 Weeks After Completion of Therapy (SVR12)
Description
SVR12 was defined as undetectable HCV RNA 12 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time Frame
Week 24 for Grazoprevir treatment arms, Week 36 for Placebo arm
Title
Number of Participants Achieving Sustained Viral Response 24 Weeks After Completion of Therapy (SVR24)
Description
SVR24 was defined as undetectable HCV RNA 24 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time Frame
Week 36 for Grazoprevir treatment arms, Week 48 for Placebo arm
Title
Number of Participants Achieving Undetectable HCV RNA at Week 12 in the Placebo Arm
Description
HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time Frame
Week 12
Title
Number of Participants Achieving Complete Early Virologic Response (cEVR) at Week 24 in the Placebo Arm
Description
cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 24 (i.e., after 12 weeks of placebo + 12 weeks of grazoprevir treatment). HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay.
Time Frame
Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Body weight ≥ 88 lbs and ≤ 275 lbs
Documented chronic Hepatitis C (CHC) GT2 or GT3 infection
No known cirrhosis
Agrees to use two acceptable methods of birth control during study and through 6 months after last dose of study drug
Chest X-ray within the last 6 months
Eye exam within the last 6 months
Exclusion Criteria:
Known to be human immunodeficiency virus (HIV) positive or co-infected with active hepatitis B virus (positive for Hepatitis B surface antigen)
Prior approved or investigational treatment for hepatitis C
Evidence of hepatocellular carcinoma
Diabetic and/or high blood pressure with clinically significant eye exam findings
Pre-existing psychiatric condition
Clinical diagnosis of abuse of certain substances within specified timeframes
Known medical condition that could interfere with participation
Active or suspected cancer within the last 5 years
Female who is pregnant, breastfeeding, or expecting to conceive or donate eggs
Male who is planning to impregnate partner or donate sperm
Male with a pregnant female partner
Chronic hepatitis not caused by HCV
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=5172-012&kw=5172-012&tab=access
Learn more about this trial
Grazoprevir (MK-5172) With Peg-Interferon and Ribavirin in Participants With Chronic Genotype 2 or 3 Hepatitis C (MK-5172-012)
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