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

• ClinicalTrials.gov Identifier: NCT03379506
• Recruitment Status: Completed
• First Posted: December 20, 2017
• Results First Posted: August 17, 2020
• Last Update Posted: July 6, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HCV Infection	Drug: EBR/GZR FDC Tablet; Drug: Placebo; Drug: Grazoprevir Oral Granules; Drug: Elbasvir Oral Granules	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 25, 2018
• Actual Primary Completion Date: October 28, 2019
• Actual Study Completion Date: July 23, 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: EBR/GZR; 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; 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.; Other Names: MK-5172A; ZEPATIER®; Drug: Placebo; Placebo tablet matched to EBR/GZR FDC tablet.; Drug: Grazoprevir Oral Granules; 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.; Other Name: MK-5172; Drug: Elbasvir Oral Granules; 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.; Other Name: MK-8742

Outcome Measures

Primary Outcome Measures :

1. Area Under the Plasma Concentration-Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of EBR at Steady State [ Time Frame: 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.
2. Maximum Plasma Concentration (Cmax) of EBR [ Time Frame: 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.
3. Steady State Predose Drug Concentration (Ctrough) of EBR [ Time Frame: Week 4: Predose ]
   The Ctrough of EBR at steady state (Week 4) was determined at steady state prior to dosing in each cohort.
4. Apparent Clearance (CL/F) of EBR at Steady State [ Time Frame: 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.
5. AUC0-24hr of GZR at Steady State [ Time Frame: 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.
6. Cmax of GZR [ Time Frame: 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.
7. Ctrough of GZR [ Time Frame: Week 4: Predose ]
   The Ctrough of GZR at steady state (Week 4) was determined at steady state prior to dosing in each cohort.
8. CL/F of GZR at Steady State [ Time Frame: 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.

Secondary Outcome Measures :

1. Percentage of Participants With ≥1 Adverse Event (AE) [ Time Frame: 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.
2. Percentage of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: 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.
3. Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12) [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California San Francisco ( Site 0020)

San Francisco, California, United States, 94158

United States, Florida

Florida Hospital ( Site 0006)

Orlando, Florida, United States, 32803

United States, Georgia

Children's Center for Advanced Pediatrics ( Site 0204)

Atlanta, Georgia, United States, 30329

United States, Massachusetts

Children's Hospital Boston ( Site 0009)

Boston, Massachusetts, United States, 02115

United States, Ohio

Cincinnati Children's Hospital Medical Center ( Site 0003)

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Children's Hospital of Pittsburgh ( Site 0024)

Pittsburgh, Pennsylvania, United States, 15224

United States, Texas

American Research Corporation ( Site 0200)

San Antonio, Texas, United States, 78215

United States, Washington

Children's Hospital and Regional Medical Center ( Site 0017)

Seattle, Washington, United States, 98105

Germany

Medizinische Hochschule Hannover Kinderklinik K10 ( Site 0105)

Hannover, Germany, 30625

Klinikum Starnberg ( Site 0107)

Starnberg, Germany, 82319

Helios Klinikum Wuppertal GmbH ( Site 0104)

Wuppertal, Germany, 42283

Poland

WSOZ im.T.Browicza w Bydgoszczy ( Site 0800)

Bydgoszcz, Poland, 85-030

Wojewodzki Specjalistyczny Szpital im. dr W. Bieganskiego w Lodzi ( Site 0810)

Lodz, Poland, 91-347

MED-POLONIA Sp. z o.o. ( Site 0808)

Poznan, Poland, 60-693

Sweden

Karolinska Universitetssjukhuset Huddinge. ( Site 0062)

Stockholm, Sweden, 141 86

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme LLC:

Study Protocol and Statistical Analysis Plan  [PDF] February 16, 2018

More Information

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03379506
• Other Study ID Numbers: 5172-079; 2015-003006-16 ( EudraCT Number ); MK-5172-079 ( Other Identifier: Merck Protocol Number )
• First Posted: December 20, 2017
• Results First Posted: August 17, 2020
• Last Update Posted: July 6, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infections; Communicable Diseases; Hepatitis C; Hepatitis C, Chronic; Disease Attributes; Pathologic Processes; Hepatitis; Liver Diseases; Digestive System Diseases; Blood-Borne Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Grazoprevir; Antiviral Agents; Anti-Infective Agents