Clinical trial NCT03067129: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hepatitis C Virus (HCV)
Keywords: Chronic Hepatitis C Virus
Glecaprevir
Pibrentasvir
Pharmacokinetic
Treatment naïve
Treatment experienced
Interferon (IFN)
Pegylated interferon (pegIFN)
Ribavirin (RBV)
Sofosbuvir
Non-cirrhotic cirrhosis
Compensated (Child-Pugh A) cirrhosis
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-03-01
Enrollment: 129
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Steady-state Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Glecaprevir
timeFrame: Week 2 from predose to 24 hours post-dose
measure: Steady-state AUC0-24 of Pibrentasvir
timeFrame: Week 2 from predose to 24 hours post-dose
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
timeFrame: 12 weeks after last dose of study drug (Week 20, 24, or 28 depending on treatment duration)
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Glecaprevir
timeFrame: Week 2 from predose to 24 hours post-dose
measure: Apparent Clearance (CL/F) of Glecaprevir From Plasma
timeFrame: Week 2 from predose to 24 hours post-dose
measure: Maximum Plasma Concentration of Pibrentasvir
timeFrame: Week 2 from predose to 24 hours post-dose
measure: Apparent Clearance of Pibrentasvir From Plasma
timeFrame: Week 2 from predose to 24 hours post-dose
measure: Percentage of Participants Who Experienced On-treatment Virologic Failure
timeFrame: Up to Week 8, 12, or 16 (depending on treatment duration)
measure: Percentage of Participants With Post-treatment Relapse up to 12 Weeks Post Treatment
timeFrame: Up to 12 weeks after the last dose of study drug (Week 20, 24, or 28 depending on treatment duration)
measure: Percentage of Participants With New Hepatitis C Virus Infection (Reinfection)
timeFrame: From the end of treatment up to post-treatment Week 144
measure: Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose?
timeFrame: Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration)
measure: Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose?
timeFrame: Final treatment visit (up to Week 8, 12, or 16, depending on duration of treatment)
measure: 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?
timeFrame: Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration)
measure: Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine?
timeFrame: Final treatment visit (up to Week 8, 12, or 16 depending on treatment duration)
measure: Palatability Questionnaire Question 4a: Type of Feeding Resistance
timeFrame: Up to final treatment visit (up to Week 8, 12, or 16 depending on treatment duration)
measure: Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine?
timeFrame: Final treatment visit (up to Week 8, 12, or 16, depending on treatment duration)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Univ of California San Francis /ID# 158002
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado /ID# 157996
state: Colorado
city: Hartford
country: United States
facility: CT Childrens Medical Ctr, US /ID# 158639
state: Connecticut
city: Gainesville
country: United States
facility: UF Hepatology Research at CTRB /ID# 158008
state: Florida
city: Orlando
country: United States
facility: Advent Health /ID# 166022
state: Florida
city: Indianapolis
country: United States
facility: Indiana University /ID# 158001
state: Indiana
city: Boston
country: United States
facility: Boston Childrens Hospital /ID# 157988
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center /ID# 157997
state: Massachusetts
city: New York
country: United States
facility: Columbia Univ Medical Center /ID# 158000
state: New York
city: Chapel Hill
country: United States
facility: UNC Health Care /ID# 157991
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hosp Med /ID# 158007
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia /ID# 158003
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Child Hosp of Pittsburgh,PA /ID# 158004
state: Pennsylvania
city: Nashville
country: United States
facility: Monroe-Carell Jr. Children's H /ID# 169037
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine /ID# 157989
state: Texas
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint Luc /ID# 162173
state: Bruxelles-Capitale
city: Leuven
country: Belgium
facility: UZ Leuven /ID# 162174
city: Calgary
country: Canada
facility: Alberta Children's Hospital /ID# 163449
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital /ID# 163450
state: Alberta
city: Toronto
country: Canada
facility: Hospital for Sick Children /ID# 163448
state: Ontario
city: Freiburg im Breisgau
country: Germany
facility: Universitatsklinikum Freiburg /ID# 165187
state: Baden-Wuerttemberg
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin /ID# 165186
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal /ID# 165185
city: Kurume-shi
country: Japan
facility: Kurume University Hospital /ID# 165718
state: Fukuoka
city: Osaka-shi
country: Japan
facility: Osaka General Medical Center /ID# 212745
state: Osaka
city: Suita-shi
country: Japan
facility: Osaka University Hospital /ID# 165709
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital /ID# 212912
state: Tokyo
city: San Juan
country: Puerto Rico
facility: San Jorge Children Hospital /ID# 160850
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution - Institute of Nutrition /ID# 163345
state: Moskva
city: Moscow
country: Russian Federation
facility: National Medical Scientific Centre of children health /ID# 163344
state: Moskva
city: Saint-petersburg
country: Russian Federation
facility: Scientific and Research Institute of pediatric infections /ID# 163343
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu /ID# 163282
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 163323
city: Madrid
country: Spain
facility: Hospital Universitario La Paz /ID# 163283
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 163325
city: Birmingham
country: United Kingdom
facility: Birmingham Childrens Hospital /ID# 162718
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hos /ID# 162719
city: London
country: United Kingdom
facility: King's College Hospital NHS /ID# 162717
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.