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

NCT ID: NCT03379506

Last Updated: 2023-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-25
• Study Completion Date: 2020-07-23

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.

Conditions

HCV Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

EBR/GZR FDC Tablet

Intervention Type: DRUG

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.

Placebo

Intervention Type: DRUG

Placebo tablet matched to EBR/GZR FDC tablet.

Grazoprevir Oral Granules

Intervention Type: DRUG

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.

Elbasvir Oral Granules

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Placebo

Placebo tablet matched to EBR/GZR FDC tablet.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

MK-5172A; ZEPATIER®; MK-5172; MK-8742

Eligibility 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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

University of California San Francisco ( Site 0020)

San Francisco, California, United States

Florida Hospital ( Site 0006)

Orlando, Florida, 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

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

Seattle, Washington, United States

Medizinische Hochschule Hannover Kinderklinik K10 ( Site 0105)

Hanover, , Germany

Klinikum Starnberg ( Site 0107)

Starnberg, , Germany

Helios Klinikum Wuppertal GmbH ( Site 0104)

Wuppertal, , 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

Countries

United States; Germany; Poland; Sweden

References

Gonzalez-Peralta RP, Wirth S, Squires RH, Mutschler F, Lang T, Pawlowska M, Sluzewski W, Majda-Stanislawska E, Fischler B, Balistreri WF, Jonas MM, Blondet N, Rosenthal P, Alkhouri N, Romero R, Grandhi A, Castronuovo P, Caro L, Du L, Rosenbloom DIS, Haber BA. Elbasvir/grazoprevir in children aged 3-18 years with chronic HCV genotype 1 or 4 infection: a pharmacokinetic modeling study. Hepatol Commun. 2023 Feb 14;7(3):e0031. doi: 10.1097/HC9.0000000000000031. eCollection 2023 Mar 1.

Reference Type: RESULT

PMID: 36790337 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-5172-079

Identifier Type: OTHER

Identifier Source: secondary_id

2015-003006-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

5172-079

Identifier Type: -

Identifier Source: org_study_id