A Study to Evaluate Treatment of Hepatitis C Virus Infection in Pediatric Subjects

Chronic Hepatitis C Infection Clinical Trial

— ZIRCON  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02486406
• Other study ID #: M14-748
• Secondary ID: 2015-000111-41
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 28, 2015
• Est. completion date: November 19, 2020

Study information

• Verified date: September 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: November 19, 2020
• Est. primary completion date: November 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis C Infection
• Communicable Diseases
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Infections

Intervention

Drug:
• Ombitasvir/paritaprevir/ritonavir
Film-coated tablet for oral use
• Dasabuvir
Film-coated tablet for oral use
• Ribavirin
Film-coated tablet for oral use
• Ombitasvir mini tablet
Film-coated tablet for oral use
• Paritaprevir mini tablet
Film-coated tablet for oral use
• Ritonavir mini tablet
Film-coated tablet for oral use
• Dasabuvir mini tablet
Film-coated tablet for oral use
• Ribavirin solution
Oral solution

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc /ID# 136910	Brussels	Bruxelles-Capitale
Belgium	UZ Leuven /ID# 136911	Leuven
Germany	Charite Universitaetsmedizin Berlin /ID# 141620	Berlin
Germany	Universitaetsklinikum Freiburg /ID# 141618	Freiburg
Germany	Helios Klinikum Wuppertal /ID# 142883	Wuppertal
Puerto Rico	San Jorge Children Hospital /ID# 136832	San Juan
Spain	Hospital Universitario Vall d'Hebron /ID# 137098	Barcelona
Spain	Hospital Sant Joan de Deu /ID# 137096	Esplugues de Llobregat	Barcelona
Spain	Hospital Universitario La Paz /ID# 137094	Madrid
Spain	Hospital Universitario y Politecnico La Fe /ID# 137097	Valencia
United States	Children's Hospital Colorado /ID# 137017	Aurora	Colorado
United States	Boston Childrens Hospital /ID# 137174	Boston	Massachusetts
United States	Boston Medical Center /ID# 136831	Boston	Massachusetts
United States	University of Florida - Archer /ID# 136830	Gainesville	Florida
United States	Baylor College of Medicine /ID# 136590	Houston	Texas
United States	Indiana University /ID# 137015	Indianapolis	Indiana
United States	Columbia Univ Medical Center /ID# 136431	New York	New York
United States	Advent Health /ID# 167663	Orlando	Florida
United States	Children's Hospital of Philadelphia /ID# 137018	Philadelphia	Pennsylvania
United States	UCSF Benioff Childrens Hosp /ID# 136774	San Francisco	California
United States	Seattle Children's Hospital /ID# 137019	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV)	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.	At Week 2
Primary	Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV)	AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ombitasvir present was measured up to 24 hours after dosing.	At Week 2
Primary	Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV)	Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.	At Weeks 2 and 8
Primary	Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV)	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.	At Week 2
Primary	Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV)	AUC is a measure of how long and how much drug is present in the body after dosing. The amount of paritaprevir present was measured up to 24 hours after dosing.	At Week 2
Primary	Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV)	Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.	At Weeks 2 and 8
Primary	Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV)	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.	At Week 2
Primary	Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV)	AUC is a measure of how long and how much drug is present in the body after dosing. The amount of dasabuvir present was measured up to 12 hours after dosing. For two subjects in the 15-29 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation. For one subject in the 30-44 kg group, the 24 h concentration was used as the 12 h concentration due to the significant sampling time deviation.	At Week 2
Primary	Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV)	Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.	At Weeks 2 and 8
Primary	Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV)	Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administrated and before administration of a second dose.	At Week 2
Primary	Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV)	AUC is a measure of how long and how much drug is present in the body after dosing. The amount of ritonavir present was measured up to 24 hours after dosing.	At Week 2
Primary	Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV)	Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.	At Weeks 2 and 8
Primary	Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12)	SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)
Secondary	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	SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)
Secondary	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	SVR24 is defined as hepatitis C virus ribonucleic acid (HCV RNA) < lower limit of quantification (LLOQ) 24 weeks after the last actual dose of study drug.	24 weeks after last dose of study drug (Week 36 or 48 depending on treatment duration)
Secondary	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	Alanine aminotransferase (ALT) normalization during treatment is defined as ALT = the upper limit of normal (ULN) at the final treatment visit for participants with ALT > ULN at baseline.	12 or 24 weeks after starting study drug, depending on treatment duration