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

NCT ID: NCT03067129

Last Updated: 2023-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 129 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-20
• Study Completion Date: 2022-09-12

Brief 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.

Detailed 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.

Conditions

Hepatitis C Virus (HCV)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: Adult Formulation; 12 to < 18 years

Adolescents aged 12 to \< 18 years old received the adult formulation of glecaprevir (GLE)/pibrentasvir (PIB) 100 mg/ 40 mg co-formulated film-coated tablets for a once daily (QD) total dose of 300 mg/120 mg by mouth for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience.

Group Type: EXPERIMENTAL

Glecaprevir/Pibrentasvir Adult Formulation

Intervention Type: DRUG

Co-formulated film-coated tablet (100 mg/40 mg)

Cohort 2: Pediatric Formulation; 9 to < 12 years

Children aged 9 to < 12 years old received a pediatric formulation of GLE + PIB as small film-coated granules taken with a small amount of food once daily for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience.

The initial proposed dose for children 9 to < 12 years old (30 to < 45 kg) was GLE 200 mg + PIB 75 mg. After PK analysis from the first 6 enrolled participants the dose was adjusted to GLE 250 mg + PIB 100 mg.

Group Type: EXPERIMENTAL

Glecaprevir + Pibrentasvir Pediatric Formulation

Intervention Type: DRUG

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.

Cohort 3: Pediatric Formulation; 6 to < 9 years

Children aged 6 to < 9 years old received a pediatric formulation of GLE + PIB as small film-coated granules taken with a small amount of food once daily for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience.

The initial proposed dose for children 6 to < 9 years old (20 to < 30 kg) was GLE 160 mg + PIB 60 mg. After PK analysis from the first 6 enrolled participants the dose was adjusted to GLE 200 mg + PIB 80 mg.

Group Type: EXPERIMENTAL

Glecaprevir + Pibrentasvir Pediatric Formulation

Intervention Type: DRUG

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.

Cohort 4: Pediatric Formulation; 3 to < 6 years

Children aged 3 to < 6 years old received a pediatric formulation of GLE + PIB as small film-coated granules taken with a small amount of food once daily for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience.

The initial proposed dose for children 3 to < 6 years old (12 to < 20 kg) was GLE 120 mg + PIB 45 mg. After PK analysis from the first 5 enrolled participants the dose was adjusted to GLE 150 mg + PIB 60 mg.

Group Type: EXPERIMENTAL

Glecaprevir + Pibrentasvir Pediatric Formulation

Intervention Type: DRUG

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.

Interventions

Glecaprevir/Pibrentasvir Adult Formulation

Co-formulated film-coated tablet (100 mg/40 mg)

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

ABT-493/ABT-530; MAVYRET®; ABT-493/ABT-530

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

Univ of California San Francis /ID# 158002

San Francisco, California, United States

Childrens Hospital Colorado /ID# 157996

Aurora, Colorado, United States

CT Childrens Medical Ctr, US /ID# 158639

Hartford, Connecticut, United States

UF Hepatology Research at CTRB /ID# 158008

Gainesville, Florida, United States

Advent Health /ID# 166022

Orlando, Florida, United States

Indiana University /ID# 158001

Indianapolis, Indiana, United States

Boston Childrens Hospital /ID# 157988

Boston, Massachusetts, United States

Boston Medical Center /ID# 157997

Boston, Massachusetts, United States

Columbia Univ Medical Center /ID# 158000

New York, New York, United States

UNC Health Care /ID# 157991

Chapel Hill, North Carolina, United States

Cincinnati Childrens Hosp Med /ID# 158007

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia /ID# 158003

Philadelphia, Pennsylvania, United States

Child Hosp of Pittsburgh,PA /ID# 158004

Pittsburgh, Pennsylvania, United States

Monroe-Carell Jr. Children's H /ID# 169037

Nashville, Tennessee, United States

Baylor College of Medicine /ID# 157989

Houston, Texas, United States

Cliniques Universitaires Saint Luc /ID# 162173

Woluwe-Saint-Lambert, Brussels Capital, Belgium

UZ Leuven /ID# 162174

Leuven, , Belgium

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, Canada

Universitatsklinikum Freiburg /ID# 165187

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Charite Universitaetsmedizin Berlin /ID# 165186

Berlin, , Germany

Helios Klinikum Wuppertal /ID# 165185

Wuppertal, , Germany

Kurume University Hospital /ID# 165718

Kurume-shi, Fukuoka, Japan

Osaka General Medical Center /ID# 212745

Osaka, Osaka, Japan

Osaka University Hospital /ID# 165709

Suita-shi, Osaka, Japan

Juntendo University Hospital /ID# 212912

Bunkyo-ku, Tokyo, Japan

San Jorge Children Hospital /ID# 160850

San Juan, , Puerto Rico

Federal State Budgetary Institution - Institute of Nutrition /ID# 163345

Moscow, Moscow, Russia

National Medical Scientific Centre of children health /ID# 163344

Moscow, Moscow, Russia

Scientific and Research Institute of pediatric infections /ID# 163343

Saint Petersburg, , Russia

Hospital Sant Joan de Deu /ID# 163282

Esplugues de Llobregat, Barcelona, Spain

Hospital Universitario Vall d'Hebron /ID# 163323

Barcelona, , Spain

Hospital Universitario La Paz /ID# 163283

Madrid, , Spain

Hospital Universitario y Politecnico La Fe /ID# 163325

Valencia, , Spain

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 Kingdom

Countries

United States; Belgium; Canada; Germany; Japan; Puerto Rico; Russia; Spain; United Kingdom

References

Jonas MM, Rhee S, Kelly DA, Del Valle-Segarra A, Feiterna-Sperling C, Gilmour S, Gonzalez-Peralta RP, Hierro L, Leung DH, Ling SC, Lobzin Y, Lobritto S, Mizuochi T, Narkewicz MR, Sabharwal V, Wen J, Kei Lon H, Marcinak J, Topp A, Tripathi R, Sokal E. Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Children With Chronic HCV: Part 2 of the DORA Study. Hepatology. 2021 Jul;74(1):19-27. doi: 10.1002/hep.31841.

Reference Type: DERIVED

PMID: 33811356 (View on PubMed)

Jonas MM, Squires RH, Rhee SM, Lin CW, Bessho K, Feiterna-Sperling C, Hierro L, Kelly D, Ling SC, Strokova T, Del Valle-Segarra A, Lovell S, Liu W, Ng TI, Porcalla A, Gonzalez YS, Burroughs M, Sokal E. Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Adolescents With Chronic Hepatitis C Virus: Part 1 of the DORA Study. Hepatology. 2020 Feb;71(2):456-462. doi: 10.1002/hep.30840. Epub 2019 Aug 13.

Reference Type: DERIVED

PMID: 31254392 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004102-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M16-123

Identifier Type: -

Identifier Source: org_study_id