A Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Pediatric Subjects With Genotypes 1-6 Chronic Hepatitis C Virus (HCV) Infection

Hepatitis C Virus (HCV) Clinical Trial

— DORA  

Official title:

An Open-Label, Multicenter Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Pediatric Subjects With Genotypes 1-6 Chronic Hepatitis C Virus (HCV) Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03067129
• Other study ID #: M16-123
• Secondary ID: 2016-004102-34
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 20, 2017
• Est. completion date: September 12, 2022

Study information

• Verified date: April 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of this study are to assess the pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir adult formulation in adolescents ages 12 to 17 years and a pediatric formulation of glecaprevir and pibrentasvir in children ages 3 to < 12 years.

Description:

This was a multicenter study to evaluate the pharmacokinetics (PK), efficacy, and safety of glecaprevir (GLE) and pibrentasvir (PIB) treatment for 8, 12, or 16 weeks in hepatitis C virus (HCV) genotype 1 - 6 (GT1 - GT6)-infected pediatric participants 3 to < 18 years of age, with or without compensated cirrhosis, with or without human immunodeficiency virus (HIV) coinfection, who are either treatment-naïve (TN), treatment-experienced (TE) with pegylated interferon (pegIFN) with or without ribavirin (RBV), or TE with sofosbuvir (SOF) + RBV with or without pegIFN.

The study was divided into 2 parts, according to the formulation of GLE/PIB administered. Part 1 of the study enrolled HCV GT1 - GT6 infected adolescent participants into the 12 to < 18 years old age group who were willing to swallow the adult formulation of GLE/PIB (Cohort 1). Part 2 of the study enrolled HCV GT1 - GT6 infected pediatric participants divided into the 9 to < 12 (Cohort 2), 6 to < 9 (Cohort 3), and 3 to < 6 (Cohort 4) years old age groups, to receive the pediatric formulation of GLE + PIB. Part 1 enrolled first and once the pediatric formulation was available enrollment into Part 2 commenced, with each cohort enrolled in parallel.

In each cohort, the first group of participants were enrolled into an intense pharmacokinetics (IPK) portion to characterize the PK and safety in each age group, followed by enrollment into a non-IPK safety/efficacy portion. Study participants enrolled in the IPK portion must have been HIV-negative, treatment-naive, and have an identified HCV genotype. In the IPK portion the first approximately six participants received an initial proposed dose of GLE and PIB based on the child's weight and age at screening. PK samples from these participants were evaluated to determine if therapeutic efficacious exposures were attained, comparable to those of adults, and if any dose adjustments were needed. After the intensive PK analysis results for the first six participants were available, enrollment of the remaining IPK portion resumed with subsequent participants receiving an adjusted final dose as applicable. Additional participants may have been required for further intensive PK analysis per age cohort if therapeutic exposure targets were not achieved.

Enrollment into the non-IPK safety and efficacy portions began when the dosing recommendations per age group based on the PK and clinical data from the IPK analysis were ascertained.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 129
• Est. completion date: September 12, 2022
• Est. primary completion date: May 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 17 Years

Eligibility

Inclusion Criteria:

• Hepatitis C virus (HCV) infection demonstrated by positive anti-HCV antibody (Ab) and HCV ribonucleic acid (RNA) greater than or equal to 1000 International Unit (IU)/mL

• Subjects participating in the intense pharmacokinetic (IPK) part must have been HCV treatment-naive, with or without compensated cirrhosis (Child-Pugh A), human immunodeficiency virus type 1 (HIV-1) negative and must have had a Screening laboratory result indicating HCV genotype (GT) 1, 2, 3, 4, 5, or 6-infection.

Exclusion Criteria:

• Females who were pregnant or breastfeeding

• Positive test result for hepatitis B surface antigen (HbsAg) or positive test result for hepatitis B virus deoxyribonucleic acid (DNA)

• Participants with other known liver diseases

• Decompensated cirrhosis defined as: presence of ascites, history of variceal bleeding, lab values consistent with Child-Pugh class B or C cirrhosis

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus (HCV)
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Glecaprevir/Pibrentasvir Adult Formulation
Co-formulated film-coated tablet (100 mg/40 mg)
• Glecaprevir + Pibrentasvir Pediatric Formulation
Film-coated pellets/granules (15.67%/8.25%) administered by mixing with a small amount (1-2 teaspoons) of a soft food vehicle, such as hazelnut spread, Greek yogurt, or peanut butter.

Locations

Country	Name	City	State
Belgium	UZ Leuven /ID# 162174	Leuven
Belgium	Cliniques Universitaires Saint Luc /ID# 162173	Woluwe-Saint-Lambert	Bruxelles-Capitale
Canada	Alberta Children's Hospital /ID# 163449	Calgary	Alberta
Canada	Stollery Children's Hospital /ID# 163450	Edmonton	Alberta
Canada	Hospital for Sick Children /ID# 163448	Toronto	Ontario
Germany	Charite Universitaetsmedizin Berlin /ID# 165186	Berlin
Germany	Universitatsklinikum Freiburg /ID# 165187	Freiburg im Breisgau	Baden-Wuerttemberg
Germany	Helios Klinikum Wuppertal /ID# 165185	Wuppertal
Japan	Juntendo University Hospital /ID# 212912	Bunkyo-ku	Tokyo
Japan	Kurume University Hospital /ID# 165718	Kurume-shi	Fukuoka
Japan	Osaka General Medical Center /ID# 212745	Osaka-shi	Osaka
Japan	Osaka University Hospital /ID# 165709	Suita-shi	Osaka
Puerto Rico	San Jorge Children Hospital /ID# 160850	San Juan
Russian Federation	Federal State Budgetary Institution - Institute of Nutrition /ID# 163345	Moscow	Moskva
Russian Federation	National Medical Scientific Centre of children health /ID# 163344	Moscow	Moskva
Russian Federation	Scientific and Research Institute of pediatric infections /ID# 163343	Saint-petersburg
Spain	Hospital Universitario Vall d'Hebron /ID# 163323	Barcelona
Spain	Hospital Sant Joan de Deu /ID# 163282	Esplugues de Llobregat	Barcelona
Spain	Hospital Universitario La Paz /ID# 163283	Madrid
Spain	Hospital Universitario y Politecnico La Fe /ID# 163325	Valencia
United Kingdom	Birmingham Childrens Hospital /ID# 162718	Birmingham
United Kingdom	Queen Elizabeth University Hos /ID# 162719	Glasgow
United Kingdom	King's College Hospital NHS /ID# 162717	London
United States	Childrens Hospital Colorado /ID# 157996	Aurora	Colorado
United States	Boston Childrens Hospital /ID# 157988	Boston	Massachusetts
United States	Boston Medical Center /ID# 157997	Boston	Massachusetts
United States	UNC Health Care /ID# 157991	Chapel Hill	North Carolina
United States	Cincinnati Childrens Hosp Med /ID# 158007	Cincinnati	Ohio
United States	UF Hepatology Research at CTRB /ID# 158008	Gainesville	Florida
United States	CT Childrens Medical Ctr, US /ID# 158639	Hartford	Connecticut
United States	Baylor College of Medicine /ID# 157989	Houston	Texas
United States	Indiana University /ID# 158001	Indianapolis	Indiana
United States	Monroe-Carell Jr. Children's H /ID# 169037	Nashville	Tennessee
United States	Columbia Univ Medical Center /ID# 158000	New York	New York
United States	Advent Health /ID# 166022	Orlando	Florida
United States	Children's Hospital of Philadelphia /ID# 158003	Philadelphia	Pennsylvania
United States	Child Hosp of Pittsburgh,PA /ID# 158004	Pittsburgh	Pennsylvania
United States	Univ of California San Francis /ID# 158002	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Japan,  Puerto Rico,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Steady-state Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Glecaprevir	The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma. The steady-state exposure of GLE was measured up to 24 hours after dosing at Week 2 and estimated using non-compartmental analysis.	Week 2 from predose to 24 hours post-dose
Primary	Steady-state AUC0-24 of Pibrentasvir	The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma. The steady-state exposure of PIB was measured up to 24 hours after dosing at Week 2 and estimated using non-compartmental analysis.	Week 2 from predose to 24 hours post-dose
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12)	SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last actual dose of study drug. Plasma HCV RNA levels were collected using the COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test v2.0.; SVR12 was considered a primary efficacy endpoint by the United States (US) regulatory agency and was considered secondary outside of the US.	12 weeks after last dose of study drug (Week 20, 24, or 28 depending on treatment duration)
Secondary	Maximum Plasma Concentration (Cmax) of Glecaprevir	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administered and before administration of a second dose.	Week 2 from predose to 24 hours post-dose
Secondary	Apparent Clearance (CL/F) of Glecaprevir From Plasma	CL/F is a quantitative measure of the rate at which a drug substance is removed from the body. It was estimated by non-compartmental pharmacokinetic analysis.	Week 2 from predose to 24 hours post-dose
Secondary	Maximum Plasma Concentration of Pibrentasvir	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administered and before administration of a second dose.	Week 2 from predose to 24 hours post-dose
Secondary	Apparent Clearance of Pibrentasvir From Plasma	CL/F is a quantitative measure of the rate at which a drug substance is removed from the body. It was estimated by non-compartmental pharmacokinetic analysis.	Week 2 from predose to 24 hours post-dose
Secondary	Percentage of Participants Who Experienced On-treatment Virologic Failure	On-treatment virologic failure is defined as meeting one of the following: A confirmed (defined as two consecutive HCV RNA measurements) increase of > 1 log10 IU/mL above nadir during treatment; Confirmed HCV RNA = 100 IU/mL after HCV RNA < 15 IU/mL during treatment; HCV RNA = 15 IU/mL at the end of treatment with at least 6 weeks of treatment.	Up to Week 8, 12, or 16 (depending on treatment duration)
Secondary	Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment	Post-treatment relapse is defined as confirmed HCV RNA = 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA < 15 IU/mL at the end of treatment; excluding participants who had been shown to be re-infected.	Up to 12 weeks after the last dose of study drug (Week 20, 24, or 28 depending on treatment duration)
Secondary	Percentage of Participants With New Hepatitis C Virus Infection (Reinfection)	Reinfection is defined as confirmed HCV RNA = 15 IU/mL in the post-treatment period in a participant who had HCV RNA < 15 IU/mL at the Final Treatment Visit, along with post-treatment detection of a different HCV genotype, subtype, or clade compared with Baseline, as determined by phylogenetic analysis of the nonstructural viral protein 3 (NS3) or NS5A, and/or NS5B gene sequences.	From the end of treatment up to post-treatment Week 144
Secondary	Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose?	For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation.; Question 1 "How Convenient or Inconvenient Was it to Prepare the Dose?" was answered as "very convenient", "convenient", "borderline", "inconvenient", or "very inconvenient".	Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration)
Secondary	Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose?	For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation.; Question 2 "How Long Did it Typically Take for the Child to Take the Dose?" was answered as "5 minutes or less", "5 to 15 minutes", "15 to 30 minutes", or "more than 30 minutes".	Final treatment visit (up to Week 8, 12, or 16, depending on duration of treatment)
Secondary	Palatability Questionnaire Question 3: Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food?	For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation.; Question 3 "Were You Able to Successfully Administer the Whole Dose to the Child With 1 to 2 Teaspoons (5 to 10 mL) of Soft Food?" was answered as "Yes" or "No".	Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration)
Secondary	Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine?	For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 4 "Did You Experience Any Resistance When Feeding the Child the Medicine?" was answered as "Yes" or "No".	Final treatment visit (up to Week 8, 12, or 16 depending on treatment duration)
Secondary	Palatability Questionnaire Question 4a: Type of Feeding Resistance	For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE + PIB formulation. Question 4a "Type of feeding resistance?" tracks feeding resistance experienced at any time during treatment, and was answered as "Did not like taste of medicine", "Did not like texture of medicine", "Did not like the soft food used", "Did not like to swallow the amount of medicine", or "Unrelated to the medicine".	Up to final treatment visit (up to Week 8, 12, or 16 depending on treatment duration)
Secondary	Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine?	For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE/PIB formulation. Question 5 "How Easy or Difficult Was it for the Child to Swallow the Medicine?" was answered as "very easy", "easy", "borderline", "difficult", or "very difficult."	Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration)