Clinical trial NCT02486406: A Study to Evaluate Treatment of Hepatitis C Virus Infection in Pediatric Subjects
Official title: An Open-Label, Multicenter Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Ombitasvir (OBV), Paritaprevir (PTV), Ritonavir (RTV) With or Without Dasabuvir (DSV) and With or Without Ribavirin (RBV) in Pediatric Subjects With Genotype 1 or 4 Chronic Hepatitis C Virus (HCV) Infection (ZIRCON)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Chronic Hepatitis C Infection
Keywords: Hepatitis C Virus
Hepatitis C Genotype 1
Hepatitis C Genotype 4
Pediatric
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2015-07-01
Enrollment: 64
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: This was a Phase 2/3, open-label, multicenter study to evaluate the pharmacokinetics (PK), efficacy, and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/RTV) with or without dasabuvir (DSV) and with or without ribavirin (RBV) in Hepatitis C virus (HCV) genotype 1 or 4 (GT1 or GT4)-infected pediatric participants of ≥ 3 to 17 years of age.

Detailed description: The study population for Part 1, the PK study, included GT1-infected participants who were noncirrhotic and treatment-naïve (TN). Part 2, the safety and efficacy study, included GT1 or GT4-infected participants who were TN or interferon (\[IFN\] or Pegylated-interferon alfa-2a or 2b \[pegIFN\] with or without RBV) treatment-experienced (TE) without cirrhosis or with compensated cirrhosis. In Part 1 and Part 2, the treatment regimen and duration were dependent on HCV GT, GT1 subtype, and cirrhosis status.

Eligibility criteria: Inclusion Criteria:

1. Positive anti-hepatitis C virus antibody (HCV Ab) and HCV ribonucleic acid (RNA) ≥ 1000 IU/mL at the time of screening
2. HCV genotype 1 for enrollment into Part 1 of the study and genotype 1 or 4 for enrollment into Part 2
3. Parent or legal guardian with the willingness and ability to provide written informed consent and participant willing and able to give assent, as appropriate for age and country

Exclusion Criteria:

1. Female participant who is pregnant, breastfeeding or is considering becoming pregnant
2. Use of known strong inducers and inhibitors (e.g., gemfibrozil) of cytochrome P450 2C8 (CYP2C8) in participants receiving dasabuvir, or strong or moderate inducers of CYP3A, within 2 weeks or 10 half-lives, whichever is longer, of the respective medication/supplement prior to study drug administration.
3. Positive test result for Hepatitis B surface antigen (HbsAg) or anti-human immunodeficiency virus antibody (HIV Ab) test
4. Current enrollment in another interventional clinical study, previous enrollment in this study, prior or current use of any investigational or commercially available anti-HCV agents other than interferons or ribavirin or receipt of any investigational product within 6 weeks prior to study drug administration

Primary outcomes:
measure: Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV)
timeFrame: At Week 2
measure: Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV)
timeFrame: At Week 2
measure: Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV)
timeFrame: At Weeks 2 and 8
measure: Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV)
timeFrame: At Week 2
measure: Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV)
timeFrame: At Week 2
measure: Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV)
timeFrame: At Weeks 2 and 8
measure: Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV)
timeFrame: At Week 2
measure: Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV)
timeFrame: At Week 2
measure: Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV)
timeFrame: At Weeks 2 and 8
measure: Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV)
timeFrame: At Week 2
measure: Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV)
timeFrame: At Week 2
measure: Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV)
timeFrame: At Weeks 2 and 8
measure: Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12)
timeFrame: 12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)
Secondary outcomes:
measure: Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12) Summarized by Formulation, Age and Weight Group, and Across All Subjects on the Adult Formulations
timeFrame: 12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)
measure: Parts 1 & 2: Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Actual Dose of Study Drug (SVR24), Summarized by Formulation, Age and Weight Group, Across All Subjects, and Across All Subjects on the Adult Formulations
timeFrame: 24 weeks after last dose of study drug (Week 36 or 48 depending on treatment duration)
measure: Parts 1 and 2: Percentage of Participants With Alanine Aminotransferase (ALT) Normalization During Treatment by Formulation, Age and Weight Group, Across All Subjects, and Across All Subjects on the Adult Formulations
timeFrame: 12 or 24 weeks after starting study drug, depending on treatment duration
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Benioff Childrens Hosp /ID# 136774
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado /ID# 137017
state: Colorado
city: Gainesville
country: United States
facility: University of Florida - Archer /ID# 136830
state: Florida
city: Orlando
country: United States
facility: Advent Health /ID# 167663
state: Florida
city: Indianapolis
country: United States
facility: Indiana University /ID# 137015
state: Indiana
city: Boston
country: United States
facility: Boston Childrens Hospital /ID# 137174
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center /ID# 136831
state: Massachusetts
city: New York
country: United States
facility: Columbia Univ Medical Center /ID# 136431
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia /ID# 137018
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine /ID# 136590
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital /ID# 137019
state: Washington
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc /ID# 136910
state: Bruxelles-Capitale
city: Leuven
country: Belgium
facility: UZ Leuven /ID# 136911
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin /ID# 141620
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg /ID# 141618
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal /ID# 142883
city: San Juan
country: Puerto Rico
facility: San Jorge Children Hospital /ID# 136832
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu /ID# 137096
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 137098
city: Madrid
country: Spain
facility: Hospital Universitario La Paz /ID# 137094
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 137097
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Rosenthal P, Narkewicz MR, Yao BB, Jolley CD, Lobritto SJ, Wen J, Molleston JP, Hsu EK, Jonas MM, Zha J, Liu L, Leung DH. Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir Mini-Tabs Plus Ribavirin for Children Aged 3-11 Years with Hepatitis C Genotype 1a. Adv Ther. 2020 Jul;37(7):3299-3310. doi: 10.1007/s12325-020-01389-9. Epub 2020 May 25.