Safety and Efficacy of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in Participants With Chronic Hepatitis C and Chronic Kidney Disease (MK-5172-052)

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of combination treatment with grazoprevir (MK-5172) + elbasvir (MK-8742) for cirrhotic and non-cirrhotic participants with chronic Genotype 1 (GT1) hepatitis C virus (HCV) infection and chronic kidney disease (CKD). The primary study hypothesis is that the proportion of HCV GT1-infected CKD participants within the Immediate Treatment and Intensive Pharmacokinetics (PK) groups achieving a sustained viral response 12 weeks after the end of all study treatment (SVR12) will be >45%.

Official Title
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A Phase II/III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic Hepatitis C Virus Infection and Chronic Kidney Disease

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: Grazoprevir
* Drug: Elbasvir
* Drug: Placebo to Grazoprevir
* Drug: Placebo to Elbasvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented chronic (at least 6 months) HCV GT 1 infection (with no evidence of mixed genotypes or genotype that cannot be assigned a type) Evidence or no evidence of liver cirrhosis based on one of the following: Liver biopsy performed within 24 months of Day 1 (if participant is cirrhotic then there is no time restriction on biopsy) Fibroscan performed within 12 months of Day 1 of this study Fibrosure™ (Fibrotest™) plus aspartate aminotransferase to platelet Ratio Index [APRI] obtained during the screening period) Has HCV status that is one of the following: Treatment naïve Prior interferon or pegylated interferon with or without ribavarin failures (null responder, partial responder, or relapser) Intolerant to prior interferon or pegylated intereferon with or without ribavarin regimen Chronic kidney disease (defined as glomerular filtration rate [eGFR] <=29) non-dialysis dependent or on hemodialysis for at least 3 months, including individuals awaiting kidney transplant and those with failed kidney transplants but no longer on immunosuppressant therapy) Female participant of reproductive potential must agree to remain abstinent or use (or have their partner use) 2 acceptable methods of contraception from at least 2 weeks prior to Day 1 through 14 days after the last dose of study drugs, or longer if dictated by local regulations Exclusion Criteria: Evidence of decompensated liver disease On peritoneal dialysis for management of kidney disease Co-infection with hepatitis B virus or human immunodeficiency virus (HIV) History of malignancy <=5 years prior to signing informed consent Clinical diagnosis of substance abuse Pregnant, breast-feeding, expecting to conceive or donate eggs, or donate sperm from Day 1 through 14 days after the last study dose, or longer if dictated by local regulations Organ transplant (including hematopoietic stem cell transplant) other than kidney, cornea, and hair Conditions requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial Uncontrolled or poorly controlled hypertension Significant cardiovascular disorder (e.g. myocardial infarction or unstable angina) or cardiovascular procedure within 3 months prior to signing informed consent New or worsening signs or symptoms of congestive heart failure within 3 months of signing informed consent Severe active peripheral vascular disease Recent (within 3 months prior to signing informed consent) episode or recurrence of stroke, transient ischemic attack (TIA) or neurological disorder, including but not limited to seizures Evidence or history of chronic hepatitis not caused by HCV

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate Treatment<br>Participants receive grazoprevir 100 mg tablet, orally, once per day (QD) + elbasvir 50 mg tablet, orally, QD, for 12 weeks. | Drug: Grazoprevir<br>* Grazoprevir 100 mg tablet<br>* Other names: MK-5172;Drug: Elbasvir<br>* Elbasvir 50 mg tablet<br>* Other names: MK-8742;|
| Experimental: Deferred Treatment<br>Participants receive placebos to both grazoprevir and elbasvir for 12 weeks, and after a 4-week break, grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks. | Drug: Grazoprevir<br>* Grazoprevir 100 mg tablet<br>* Other names: MK-5172;Drug: Elbasvir<br>* Elbasvir 50 mg tablet<br>* Other names: MK-8742;Drug: Placebo to Grazoprevir<br>* Placebo tablet matched to grazoprevir<br>Drug: Placebo to Elbasvir<br>* Placebo tablet matched to elbasvir<br>|
| Experimental: Intensive PK<br>Participants receive grazoprevir 100 mg tablet, orally, QD + elbasvir 50 mg tablet, orally, QD for 12 weeks with intensive PK testing. | Drug: Grazoprevir<br>* Grazoprevir 100 mg tablet<br>* Other names: MK-5172;Drug: Elbasvir<br>* Elbasvir 50 mg tablet<br>* Other names: MK-8742;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12) | SVR12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) lower than the limit of quantification (LLoQ) 12 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL. | Week 24 (Immediate Treatment + Intensive PK) or Week 40 (Deferred Treatment) | 
| Number of Participants Experiencing an Adverse Event (AE) During the Initial Treatment and 14-day Follow-up Periods | 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. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group. | Up to Week 14 | 
| Number of Participants Discontinuing Study Drug Due to AEs During the Initial Treatment Period | 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. This analysis includes the Immediate Treatment + Intensive PK group and the placebo treatment period for the Deferred Treatment group. | Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24) | SVR24 was defined as HCV RNA <LLoQ 24 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL. | Week 36 (Immediate Treatment + Intensive PK) or Week 52 (Deferred Treatment) | 
| Percentage of Participants With Sustained Virologic Response 4 Weeks After Completing Study Therapy (SVR4) | SVR4 was defined as HCV RNA <LLoQ 4 weeks after completing study therapy. HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0®, which has a LLoQ of 15 IU/mL. | Week 16 (Immediate Treatment + Intensive PK) or Week 32 (Deferred Treatment) |