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

HCV Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03379506
• Other study ID #: 5172-079
• Secondary ID: MK-5172-0792015-
• Status: Completed
• Phase: Phase 2
• Start date: January 25, 2018
• Est. completion date: July 23, 2020

Study information

• Verified date: May 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: July 23, 2020
• Est. primary completion date: October 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HCV Infection
• Hepatitis C
• Hepatitis C, Chronic
• Infections

Intervention

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.
• Placebo
Placebo tablet matched to EBR/GZR FDC tablet.
• 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.
• 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.

Locations

Country	Name	City	State
Germany	Medizinische Hochschule Hannover Kinderklinik K10 ( Site 0105)	Hannover
Germany	Klinikum Starnberg ( Site 0107)	Starnberg
Germany	Helios Klinikum Wuppertal GmbH ( Site 0104)	Wuppertal
Poland	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
Sweden	Karolinska Universitetssjukhuset Huddinge. ( Site 0062)	Stockholm
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	Florida Hospital ( Site 0006)	Orlando	Florida
United States	Children's Hospital of Pittsburgh ( Site 0024)	Pittsburgh	Pennsylvania
United States	American Research Corporation ( Site 0200)	San Antonio	Texas
United States	University of California San Francisco ( Site 0020)	San Francisco	California
United States	Children's Hospital and Regional Medical Center ( Site 0017)	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Germany,  Poland,  Sweden, 

References & 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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