Elbasvir (EBR)/Grazoprevir (GZR) in Pediatric Participants With Chronic Hepatitis C Infection (MK-5172-079)

Study Overview
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Brief Summary
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The purpose of this study is to assess the pharmacokinetics (PK), safety, and efficacy of oral MK-5172 (a fixed dose combination [FDC] tablet containing elbasvir [EBR] 50 mg and grazoprevir [GZR] 100 mg) and EBR/GZR (varying doses) pediatric granules in pediatric hepatitis C virus (HCV)-infected participants who are 3 to <18 years of age. Within each age cohort (Cohort 1: 12 to <18 years of age; Cohort 2: 7 to <12 years of age; and Cohort 3: 3 to <7 years of age), a Mini Cohort of 7 participants will be enrolled first. For the oldest cohort (Cohort 1), the Mini Cohort will assess ability to swallow a placebo tablet prior to administering active FDC tablets; participants in Cohorts 2 and 3 will take pediatric granules instead of a tablet.

Official Title
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A Phase IIb Clinical Study to Assess the Pharmacokinetics, Safety, and Efficacy of the Combination Regimen of Elbasvir (EBR)/Grazoprevir (GZR) in Participants Aged 3 to Less Than 18 Years With Chronic Hepatitis C Infection

Conditions
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HCV Infection

Intervention / Treatment
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* Drug: EBR/GZR FDC Tablet
* Drug: Placebo
* Drug: Grazoprevir Oral Granules
* Drug: Elbasvir Oral Granules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has documented chronic HCV genotype (GT) 1 or GT4 infection Has the following liver disease staging assessment: absence of cirrhosis or compensated cirrhosis Has one of the following HCV treatment statuses: GT1 and GT4: treatment-naïve (TN), defined as no prior exposure to any interferon (IFN)-containing regimen, ribavirin (RBV), or other HCV-specific direct acting antiviral (DAA) agent GT1 only: treatment-experienced (TE) with no previous treatment with HCV specific DAA agents. If female is not pregnant, not breastfeeding, and is either not of childbearing potential or follows the contraceptive guidance during the treatment period and for at least 14 days after the last dose of study treatment. Exclusion Criteria: Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of advanced liver disease. Is cirrhotic AND has a Child-Turcotte-Pugh score >6, corresponding to a Child Class B or C. Is co-infected with Human Immunodeficiency Virus (HIV). Has evidence of past or present hepatitis B infection. Has a history of malignancy ≤5 years prior to signing informed consent or is under evaluation for other active or suspected malignancy. Female expects to conceive or donate eggs from Day 1 through at least 14 days after the last dose of study treatment or longer. Has any of the following conditions: organ transplants other than cornea and hair; poor venous access; history of gastric surgery or malabsorption disorders; any clinically significant cardiac abnormalities/dysfunction that may interfere with participant treatment, assessment, or compliance; any major medical condition which might interfere with participant treatment, assessment, or compliance; history of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment; medical/surgical conditions that may result in a need for hospitalization during the study duration; any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor antagonists, or immunosuppressant drugs; life-threatening serious adverse event (SAE) during the screening period; history of chronic hepatitis not caused by HCV. If female has a positive urine pregnancy test within 24 hours before the first dose of study treatment. Is taking or plans to take prohibited medications, or is taking herbal supplements. Has had previous HCV direct acting antiviral (DAA) treatment. Is currently participating or has participated in a study with an investigational compound within prior 30 days Has significant emotional problems or a clinically significant psychiatric disorder that may interfere with participant treatment, assessment, or compliance with the protocol. Has clinically relevant drug or alcohol abuse within prior 12 months that may interfere with participant treatment, assessment, or compliance.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBR/GZR<br>Pediatric participants receive EBR/GZR as either FDC tablets or oral granules once daily for 12 weeks. A 24-week follow-up period will follow the 12-week treatment regimen. | Drug: EBR/GZR FDC Tablet<br>* Participants who are 12 to <18 years of age will receive oral FDC tablets with EBR 50 mg/GZR 100 mg once daily by mouth.<br>* Other names: ZEPATIER®;Drug: Placebo<br>* Placebo tablet matched to EBR/GZR FDC tablet.<br>Drug: Grazoprevir Oral Granules<br>* Participants 3 to <12 years of age take grazoprevir granules 0.5 mg by mouth in a soft food vehicle at a dose not to exceed 50 mg.<br>* Other names: MK-5172;Drug: Elbasvir Oral Granules<br>* Participants 3 to <12 years of age take elbasvir oral granules 1 mg by mouth in a soft food vehicle at a dose not to exceed 100 mg.<br>* Other names: MK-8742;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of EBR at Steady State | The AUC0-24hr of EBR at steady state (Week 4) was determined in each cohort. | Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose | 
| Maximum Plasma Concentration (Cmax) of EBR | The Cmax of EBR at steady state (Week 4) was determined in each cohort. | Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose | 
| Steady State Predose Drug Concentration (Ctrough) of EBR | The Ctrough of EBR at steady state (Week 4) was determined at steady state prior to dosing in each cohort. | Week 4: Predose | 
| Apparent Clearance (CL/F) of EBR at Steady State | The CL/F of EBR at steady state (Week 4) was determined in each cohort. | Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose | 
| AUC0-24hr of GZR at Steady State | The AUC0-24hr of GZR at steady state (Week 4) was determined in each cohort. | Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose | 
| Cmax of GZR | The Cmax of GZR at steady state (Week 4) was determined in each cohort. | Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose | 
| Ctrough of GZR | The Ctrough of GZR at steady state (Week 4) was determined at steady state prior to dosing in each cohort. | Week 4: Predose | 
| CL/F of GZR at Steady State | The CL/F of GZR at steady state (Week 4) was determined in each cohort. | Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥1 Adverse Event (AE) | The percentage of participants with ≥1 AE is reported in each cohort. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Up to 36 weeks | 
| Percentage of Participants Discontinuing Study Treatment Due to an AE | The percentage of participants discontinuing study therapy due to an AE is reported in each cohort. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Up to 12 weeks | 
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) | The percentage of participants achieving SVR12, defined as hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantification (LLOQ) 12 weeks after completing study therapy, was determined in each cohort. | Week 24 |