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

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

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 Drug: Placebo Phase 2

Detailed Description:
The present results disclosure includes the sustained virologic response 12 weeks after completing treatment (SVR12) endpoint data with a cutoff date of 10 April 2020. Study results will be updated once the final data analysis has completed.

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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

Resource links provided by the National Library of Medicine


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
Participants who are 12 to <18 years of age will receive oral FDC tablets with EBR 50 mg/GZR 100 mg once daily. Participants who are 3 to <12 years of age will receive oral granules in a soft food vehicle (not to exceed EBR/GRZ 50 mg/100 mg) once daily.
Other Names:
  • MK-5172
  • ZEPATIER®

Drug: Placebo
Placebo tablet matched to EBR/GZR FDC tablet.




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 14 weeks (12 weeks of treatment + first 14 days of follow-up) ]
    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.



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03379506


Locations
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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 Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:
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Responsible Party: Merck Sharp & Dohme Corp.
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    Key Record Dates
Results First Posted: August 17, 2020
Last Update Posted: August 17, 2020
Last Verified: August 2020
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis, Chronic
MK-5172
Antiviral Agents
Anti-Infective Agents