Elbasvir (EBR)/Grazoprevir (GZR) in Pediatric Participants With Chronic Hepatitis C Infection (MK-5172-079)
- Conditions
- HCV Infection
- Interventions
- Registration Number
- NCT03379506
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 57
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description EBR/GZR Grazoprevir Oral Granules 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. EBR/GZR EBR/GZR FDC Tablet 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. EBR/GZR Placebo 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. EBR/GZR Elbasvir Oral Granules 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.
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration-Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of EBR at Steady State Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose The AUC0-24hr of EBR at steady state (Week 4) was determined in each cohort.
Steady State Predose Drug Concentration (Ctrough) of EBR Week 4: Predose The Ctrough of EBR at steady state (Week 4) was determined at steady state prior to dosing in each cohort.
Maximum Plasma Concentration (Cmax) of EBR Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose The Cmax of EBR at steady state (Week 4) was determined in each cohort.
AUC0-24hr of GZR at Steady State Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose The AUC0-24hr of GZR at steady state (Week 4) was determined in each cohort.
Ctrough of GZR Week 4: Predose The Ctrough of GZR at steady state (Week 4) was determined at steady state prior to dosing in each cohort.
CL/F of GZR at Steady State Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose The CL/F of GZR at steady state (Week 4) was determined in each cohort.
Apparent Clearance (CL/F) of EBR at Steady State Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose The CL/F of EBR at steady state (Week 4) was determined in each cohort.
Cmax of GZR Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose The Cmax of GZR at steady state (Week 4) was determined in each cohort.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With ≥1 Adverse Event (AE) Up to 36 weeks 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.
Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) Week 24 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.
Percentage of Participants Discontinuing Study Treatment Due to an AE Up to 12 weeks 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.
Trial Locations
- Locations (15)
University of California San Francisco ( Site 0020)
🇺🇸San Francisco, California, United States
Children's Hospital and Regional Medical Center ( Site 0017)
🇺🇸Seattle, Washington, United States
Children's Center for Advanced Pediatrics ( Site 0204)
🇺🇸Atlanta, Georgia, United States
Children's Hospital Boston ( Site 0009)
🇺🇸Boston, Massachusetts, United States
Cincinnati Children's Hospital Medical Center ( Site 0003)
🇺🇸Cincinnati, Ohio, United States
Children's Hospital of Pittsburgh ( Site 0024)
🇺🇸Pittsburgh, Pennsylvania, United States
American Research Corporation ( Site 0200)
🇺🇸San Antonio, Texas, United States
Klinikum Starnberg ( Site 0107)
🇩🇪Starnberg, Germany
WSOZ im.T.Browicza w Bydgoszczy ( Site 0800)
🇵🇱Bydgoszcz, Poland
Wojewodzki Specjalistyczny Szpital im. dr W. Bieganskiego w Lodzi ( Site 0810)
🇵🇱Lodz, Poland
MED-POLONIA Sp. z o.o. ( Site 0808)
🇵🇱Poznan, Poland
Karolinska Universitetssjukhuset Huddinge. ( Site 0062)
🇸🇪Stockholm, Sweden
Helios Klinikum Wuppertal GmbH ( Site 0104)
🇩🇪Wuppertal, Germany
Florida Hospital ( Site 0006)
🇺🇸Orlando, Florida, United States
Medizinische Hochschule Hannover Kinderklinik K10 ( Site 0105)
🇩🇪Hannover, Germany