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
DORA
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
2 other identifiers
interventional
129
9 countries
38
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2017
Longer than P75 for phase_2
38 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 24, 2017
CompletedFirst Posted
Study publicly available on registry
March 1, 2017
CompletedStudy Start
First participant enrolled
March 20, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 21, 2020
CompletedResults Posted
Study results publicly available
July 13, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
September 12, 2022
CompletedMay 9, 2023
April 1, 2023
3.2 years
February 24, 2017
May 14, 2021
April 12, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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
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
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 Outcomes (13)
Maximum Plasma Concentration (Cmax) of Glecaprevir
Week 2 from predose to 24 hours post-dose
Apparent Clearance (CL/F) of Glecaprevir From Plasma
Week 2 from predose to 24 hours post-dose
Maximum Plasma Concentration of Pibrentasvir
Week 2 from predose to 24 hours post-dose
Apparent Clearance of Pibrentasvir From Plasma
Week 2 from predose to 24 hours post-dose
Percentage of Participants Who Experienced On-treatment Virologic Failure
Up to Week 8, 12, or 16 (depending on treatment duration)
- +8 more secondary outcomes
Study Arms (4)
Cohort 1: Adult Formulation; 12 to < 18 years
EXPERIMENTALAdolescents 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.
Cohort 2: Pediatric Formulation; 9 to < 12 years
EXPERIMENTALChildren 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.
Cohort 3: Pediatric Formulation; 6 to < 9 years
EXPERIMENTALChildren 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.
Cohort 4: Pediatric Formulation; 3 to < 6 years
EXPERIMENTALChildren 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.
Interventions
Co-formulated film-coated tablet (100 mg/40 mg)
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AbbVielead
Study Sites (38)
Univ of California San Francis /ID# 158002
San Francisco, California, 94158, United States
Childrens Hospital Colorado /ID# 157996
Aurora, Colorado, 80045, United States
CT Childrens Medical Ctr, US /ID# 158639
Hartford, Connecticut, 06106, United States
UF Hepatology Research at CTRB /ID# 158008
Gainesville, Florida, 32610-0272, United States
Advent Health /ID# 166022
Orlando, Florida, 32803, United States
Indiana University /ID# 158001
Indianapolis, Indiana, 46202, United States
Boston Childrens Hospital /ID# 157988
Boston, Massachusetts, 02115, United States
Boston Medical Center /ID# 157997
Boston, Massachusetts, 02118, United States
Columbia Univ Medical Center /ID# 158000
New York, New York, 10032-3725, United States
UNC Health Care /ID# 157991
Chapel Hill, North Carolina, 27514, United States
Cincinnati Childrens Hosp Med /ID# 158007
Cincinnati, Ohio, 45229, United States
Children's Hospital of Philadelphia /ID# 158003
Philadelphia, Pennsylvania, 19104, United States
Child Hosp of Pittsburgh,PA /ID# 158004
Pittsburgh, Pennsylvania, 15213-2583, United States
Monroe-Carell Jr. Children's H /ID# 169037
Nashville, Tennessee, 37232, United States
Baylor College of Medicine /ID# 157989
Houston, Texas, 77030-3411, United States
Cliniques Universitaires Saint Luc /ID# 162173
Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium
UZ Leuven /ID# 162174
Leuven, 3000, Belgium
Alberta Children's Hospital /ID# 163449
Calgary, Alberta, T3B 6A9, Canada
Stollery Children's Hospital /ID# 163450
Edmonton, Alberta, T6G 2X8, Canada
Hospital for Sick Children /ID# 163448
Toronto, Ontario, M5G 1X8, Canada
Universitatsklinikum Freiburg /ID# 165187
Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany
Charite Universitaetsmedizin Berlin /ID# 165186
Berlin, 10117, Germany
Helios Klinikum Wuppertal /ID# 165185
Wuppertal, 42283, Germany
Kurume University Hospital /ID# 165718
Kurume-shi, Fukuoka, 830-0011, Japan
Osaka General Medical Center /ID# 212745
Osaka, Osaka, 558-8558, Japan
Osaka University Hospital /ID# 165709
Suita-shi, Osaka, 565-0871, Japan
Juntendo University Hospital /ID# 212912
Bunkyo-ku, Tokyo, 113-8431, Japan
San Jorge Children Hospital /ID# 160850
San Juan, 00912-3310, Puerto Rico
Federal State Budgetary Institution - Institute of Nutrition /ID# 163345
Moscow, Moscow, 109240, Russia
National Medical Scientific Centre of children health /ID# 163344
Moscow, Moscow, 119296, Russia
Scientific and Research Institute of pediatric infections /ID# 163343
Saint Petersburg, 197022, Russia
Hospital Sant Joan de Deu /ID# 163282
Esplugues de Llobregat, Barcelona, 08950, Spain
Hospital Universitario Vall d'Hebron /ID# 163323
Barcelona, 08035, Spain
Hospital Universitario La Paz /ID# 163283
Madrid, 28046, Spain
Hospital Universitario y Politecnico La Fe /ID# 163325
Valencia, 46026, Spain
Birmingham Childrens Hospital /ID# 162718
Birmingham, B4 6NH, United Kingdom
Queen Elizabeth University Hos /ID# 162719
Glasgow, G514TF, United Kingdom
King's College Hospital NHS /ID# 162717
London, SE5 9RS, United Kingdom
Related Publications (2)
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.
PMID: 33811356DERIVEDJonas 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.
PMID: 31254392DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Medical Services
- Organization
- AbbVie
Study Officials
- STUDY DIRECTOR
AbbVie Inc.
AbbVie
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
February 24, 2017
First Posted
March 1, 2017
Study Start
March 20, 2017
Primary Completion
May 21, 2020
Study Completion
September 12, 2022
Last Updated
May 9, 2023
Results First Posted
July 13, 2021
Record last verified: 2023-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
- Access Criteria
- Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.