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

NCT03379506 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 5172-079MK-5172-0792015-003006-16
• Study Type: interventional
• Target: 57
• Locations: 4 countries
• Sites: 15

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

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (3)

• Percentage of Participants With ≥1 Adverse Event (AE)

  Up to 36 weeks

• Percentage of Participants Discontinuing Study Treatment Due to an AE

  Up to 12 weeks

• Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12)

  Week 24

Study Arms (1)

EBR/GZR

EXPERIMENTAL

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; Drug: Placebo; Drug: Grazoprevir Oral Granules; Drug: Elbasvir Oral Granules

Interventions

EBR/GZR FDC Tablet 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.

Also known as: MK-5172A, ZEPATIER®

EBR/GZR

Placebo DRUG

Placebo tablet matched to EBR/GZR FDC tablet.

EBR/GZR

Grazoprevir Oral Granules 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.

Also known as: MK-5172

EBR/GZR

Elbasvir Oral Granules 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.

Also known as: MK-8742

EBR/GZR

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (15)

University of California San Francisco ( Site 0020)

San Francisco, California, 94158, United States

Location

Florida Hospital ( Site 0006)

Orlando, Florida, 32803, United States

Location

Children's Center for Advanced Pediatrics ( Site 0204)

Atlanta, Georgia, 30329, United States

Location

Children's Hospital Boston ( Site 0009)

Boston, Massachusetts, 02115, United States

Location

Cincinnati Children's Hospital Medical Center ( Site 0003)

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Pittsburgh ( Site 0024)

Pittsburgh, Pennsylvania, 15224, United States

Location

American Research Corporation ( Site 0200)

San Antonio, Texas, 78215, United States

Location

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

Seattle, Washington, 98105, United States

Location

Medizinische Hochschule Hannover Kinderklinik K10 ( Site 0105)

Hanover, 30625, Germany

Location

Klinikum Starnberg ( Site 0107)

Starnberg, 82319, Germany

Location

Helios Klinikum Wuppertal GmbH ( Site 0104)

Wuppertal, 42283, Germany

Location

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

Bydgoszcz, 85-030, Poland

Location

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

Lodz, 91-347, Poland

Location

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

Poznan, 60-693, Poland

Location

Karolinska Universitetssjukhuset Huddinge. ( Site 0062)

Stockholm, 141 86, Sweden

Location

Related Publications (1)

• 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.

  PMID: 36790337 RESULT

MeSH Terms

Conditions

Hepatitis C

Interventions

elbasvir-grazoprevir drug combination; grazoprevir; elbasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: December 20, 2017
• Study Start: January 25, 2018
• Primary Completion: October 28, 2019
• Study Completion: July 23, 2020
• Last Updated: May 31, 2023
• Results First Posted: August 17, 2020

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

DE (3); SE (1); US (8); PL (3)