Clinical trial NCT03379506: Elbasvir (EBR)/Grazoprevir (GZR) in Pediatric Participants With Chronic Hepatitis C Infection (MK-5172-079)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HCV Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-12-20
Enrollment: 57
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Dosing to 24 Hours Postdose (AUC0-24hr) of EBR at Steady State
timeFrame: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Maximum Plasma Concentration (Cmax) of EBR
timeFrame: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Steady State Predose Drug Concentration (Ctrough) of EBR
timeFrame: Week 4: Predose
measure: Apparent Clearance (CL/F) of EBR at Steady State
timeFrame: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: AUC0-24hr of GZR at Steady State
timeFrame: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Cmax of GZR
timeFrame: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
measure: Ctrough of GZR
timeFrame: Week 4: Predose
measure: CL/F of GZR at Steady State
timeFrame: Week 4: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours postdose
Secondary outcomes:
measure: Percentage of Participants With ≥1 Adverse Event (AE)
timeFrame: Up to 36 weeks
measure: Percentage of Participants Discontinuing Study Treatment Due to an AE
timeFrame: Up to 12 weeks
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12)
timeFrame: Week 24
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco ( Site 0020)
state: California
city: Orlando
country: United States
facility: Florida Hospital ( Site 0006)
state: Florida
city: Atlanta
country: United States
facility: Children's Center for Advanced Pediatrics ( Site 0204)
state: Georgia
city: Boston
country: United States
facility: Children's Hospital Boston ( Site 0009)
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center ( Site 0003)
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh ( Site 0024)
state: Pennsylvania
city: San Antonio
country: United States
facility: American Research Corporation ( Site 0200)
state: Texas
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center ( Site 0017)
state: Washington
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover Kinderklinik K10 ( Site 0105)
city: Starnberg
country: Germany
facility: Klinikum Starnberg ( Site 0107)
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal GmbH ( Site 0104)
city: Bydgoszcz
country: Poland
facility: WSOZ im.T.Browicza w Bydgoszczy ( Site 0800)
city: Lodz
country: Poland
facility: Wojewodzki Specjalistyczny Szpital im. dr W. Bieganskiego w Lodzi ( Site 0810)
city: Poznan
country: Poland
facility: MED-POLONIA Sp. z o.o. ( Site 0808)
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge. ( Site 0062)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.