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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.

Tracking Information
First Submitted Date  ICMJE December 13, 2017
First Posted Date  ICMJE December 20, 2017
Results First Submitted Date  ICMJE July 29, 2020
Results First Posted Date  ICMJE August 17, 2020
Last Update Posted Date August 17, 2020
Actual Study Start Date  ICMJE January 25, 2018
Actual Primary Completion Date October 28, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 29, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2017)
  • Area under the concentration-time curve of EBR [ Time Frame: Week 4: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hr ]
    Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) of plasma EBR
  • Area under the concentration-time curve of GZR [ Time Frame: Week 4: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hr ]
    Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) of plasma GZR
  • Maximum Concentration of EBR [ Time Frame: Week 4: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hr ]
    Maximum observed concentration (Cmax) of plasma EBR
  • Maximum Concentration of GZR [ Time Frame: Week 4: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hr ]
    Maximum observed concentration (Cmax) of plasma GZR
  • Clearance of EBR [ Time Frame: Week 4: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hr ]
    Apparent clearance (CL/F) of plasma EBR
  • Clearance of GZR [ Time Frame: Week 4: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 24 hr ]
    Apparent clearance (CL/F) of plasma GZR
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2020)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2017)
  • Adverse Events (AEs) [ Time Frame: Up to 24 weeks ]
    Number of participants experiencing adverse events (AEs).
  • Discontinuations due to an AE [ Time Frame: Up to 12 weeks ]
    Number of participants discontinuing study drug due to AEs.
  • Sustained Virologic Response [ Time Frame: Week 24 ]
    Percentage of participants achieving sustained virologic response defined as HCV RNA <lower limit of quantification (LLOQ) 12 weeks after the end of all study therapy (SVR12).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Elbasvir (EBR)/Grazoprevir (GZR) in Pediatric Participants With Chronic Hepatitis C Infection (MK-5172-079)
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HCV Infection
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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.
Interventions:
  • Drug: EBR/GZR
  • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 10, 2019)
57
Original Estimated Enrollment  ICMJE
 (submitted: December 18, 2017)
56
Actual Study Completion Date  ICMJE July 23, 2020
Actual Primary Completion Date October 28, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Poland,   Sweden,   United States
Removed Location Countries Australia,   Belgium,   Czechia,   New Zealand,   Norway,   Portugal,   Romania,   Russian Federation,   Spain,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT03379506
Other Study ID Numbers  ICMJE 5172-079
2015-003006-16 ( EudraCT Number )
MK-5172-079 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP