Study of Efficacy and Safety of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Chronic Hepatitis C Participants With Child-Pugh (CP)-B Hepatic Insufficiency (MK-5172-059)
- Conditions
- Chronic Hepatitis C
- Interventions
- Registration Number
- NCT02115321
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study is being done to evaluate the efficacy and safety of the drug combination grazoprevir (GZR; MK-5172) + elbasvir (EBR; MK-8742) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1, 4, or 6 infection and who have cirrhosis and Child-Pugh (CP) score 7-9 moderate hepatic insufficiency (CP-B). The primary hypothesis is that the percentage of HCV-infected participants with hepatic insufficiency (the CP-B population) achieving sustained viral response (SVR) 12 weeks after the end of all treatment (SVR12) will be greater than 60%. Additionally, ten non-cirrhotic (NC) HCV-infected GT1 participants will also be given GZR + EBR at the beginning of the study; this will be done for the purpose of collecting plasma pharmacokinetic (PK) data in HCV GT1-infected participants who do not have hepatic insufficiency.
- Detailed Description
The study will be conducted sequentially in 3 Parts. Each participant will participate in only one Part.
Participants will be enrolled in either Part A, Part B, or Part C:
* Part A: CP-B participants will receive GZR 50 mg+ EBR 50 mg; NC participants will receive GZR 100 mg/EBR 50 mg.
* Part B: CP-B participants will receive GZR 100 mg + EBR 50 mg.
* Part C: CP-B participants will receive either GZR 50 mg or 100 mg + EBR 50 mg. Study progression from Part A to Part B and from Part B to Part C will be based upon a review of safety and efficacy in Parts A and B, respectively. Depending upon safety and efficacy in Part A, the study may progress directly from Part A to Part C using GZR 50 mg + EBR 50 mg, without performing Part B.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B: CP-B GZR 100 mg + EBR 50 mg Elbasvir CP-B participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks. Part B: CP-B GZR 100 mg + EBR 50 mg MK-5172A CP-B participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks. Part A: CP-B GZR 50 mg + EBR 50 mg Grazoprevir CP-B participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks. Part A: NC GZR 100 mg + EBR 50 mg Elbasvir NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks. Part A: NC GZR 100 mg + EBR 50 mg MK-5172A NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks. Part B: CP-B GZR 100 mg + EBR 50 mg Grazoprevir CP-B participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks. Part C: CP-B GZR 50 mg or 100 mg + EBR 50 mg MK-5172A CP-B participants take GZR 50 mg or GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks (GZR dose chosen based on results of Part A CP-B arm). Part A: CP-B GZR 50 mg + EBR 50 mg Elbasvir CP-B participants take GZR 50 mg + EBR 50 mg once daily (q.d.) by mouth for 12 weeks. Part A: NC GZR 100 mg + EBR 50 mg Grazoprevir NC participants take GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks. Part C: CP-B GZR 50 mg or 100 mg + EBR 50 mg Elbasvir CP-B participants take GZR 50 mg or GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks (GZR dose chosen based on results of Part A CP-B arm). Part C: CP-B GZR 50 mg or 100 mg + EBR 50 mg Grazoprevir CP-B participants take GZR 50 mg or GZR 100 mg + EBR 50 mg q.d. by mouth for 12 weeks (GZR dose chosen based on results of Part A CP-B arm).
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Sustained Viral Response 12 Weeks After Completing Study Therapy (SVR12) Week 24 SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels below the lower limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Number of Participants Experiencing an Adverse Event (AE) During Treatment and First 14 Follow-up Days Up to 14 weeks 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.
Number of Participants Discontinuing Study Drug Due to an AE Up to 12 weeks 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With HCV RNA <LLoQ at Weeks 2, 4, and 12 Weeks 2, 4, and 12 HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Mean Change From Baseline in Model for End-Stage Liver Disease (MELD) Scores in CP-B Participants Baseline and Weeks 12, 24, and 36 The MELD score provides an objective and granular assessment of liver improvement as a continuous variable. The calculation of MELD score is based on three biochemical variables (serum bilirubin, creatinine and international normalized ratio \[INR\] of prothrombin time). The MELD equation is as follows: 9.57 x ln(creatinine mg/dL) +3.78 x ln(bilirubin mg/dL) +11.2 x ln (INR) + 6.43. Scores are multiplied by 10 and rounded to the nearest whole number and range from 6 (less ill) to 40 (gravely ill). MELD scores were determined at Baseline (Day 1) and again at Week 12, Follow-up (FU) Week 12 (Week 24), and FU Week 24 (Week 36). Change from baseline in MELD score = Post-baseline MELD score - baseline MELD score.
Percentage of Participants Achieving Sustained Viral Response 4 Weeks After Completing Study Therapy (SVR4) Week 16 SVR4 was defined as HCV RNA levels \<LLoQ 4 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Percentage of Participants Achieving Sustained Viral Response 24 Weeks After Completing Study Therapy (SVR24) Week 36 SVR24 was defined as HCV RNA levels \<LLoQ 24 weeks after completing study therapy. HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.
Percentage of Participants With HCV RNA Undetectable at Weeks 2, 4, and 12 Week 2, 4, and 12 HCV RNA was measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay which has a LLoQ of 15 IU/mL and a limit of detection of 15 IU/mL.