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

NCT02486406 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: M14-7482015-000111-41
• Study Type: interventional
• Target: 64
• Locations: 5 countries
• Sites: 21

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.

Conditions

Chronic Hepatitis C Infection

Keywords

Hepatitis C Virus; Hepatitis C Genotype 1; Hepatitis C Genotype 4; Pediatric

Outcome Measures

Primary Outcomes (13)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (3)

• 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

  12 weeks after last dose of study drug (Week 24 or 36 depending on treatment duration)

• 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

  24 weeks after last dose of study drug (Week 36 or 48 depending on treatment duration)

• 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

  12 or 24 weeks after starting study drug, depending on treatment duration

Study Arms (4)

Adult tablet, 12-17 yr, Part 1

EXPERIMENTAL

Participants with HCV GT1b without cirrhosis received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75 mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label.

Drug: Ombitasvir/paritaprevir/ritonavir; Drug: Dasabuvir; Drug: Ribavirin

Adult tablet, 12-17 yr, Part 2

EXPERIMENTAL

Participants with HCV GT1b received the adult 3-DAA (OBV/PTV/RTV and DSV) regimen: two 12.5 mg ombitasvir /75mg paritaprevir /50 mg ritonavir tablets taken orally every morning (QD) and one dasabuvir 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis received 12-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT1a with compensated cirrhosis received 24-week treatment with the adult 3-DAA regimen and ribavirin 200 mg tablets were administered orally per local label. Participants with HCV GT4 received 12-week treatment with the OBV/PTV/RTV formulation and ribavirin 200 mg tablets were administered orally per local label.

Drug: Ombitasvir/paritaprevir/ritonavir; Drug: Dasabuvir; Drug: Ribavirin

Mini tablet, 9-11 yr, Part 1

EXPERIMENTAL

Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.

Drug: Ombitasvir mini tablet; Drug: Paritaprevir mini tablet; Drug: Ritonavir mini tablet; Drug: Dasabuvir mini tablet; Drug: Ribavirin solution

Mini tablet, 3-8 yr, Part 1

EXPERIMENTAL

Participants with HCV GT1b without cirrhosis were to receive the mini-tablet 3-DAA (OBV, PTV, RTV, and DSV) regimen for 12 weeks: ombitasvir 0.3 mg, paritaprevir 1.0 mg, and ritonavir 1.0 mg mini-tablets administered orally QD based on body weight and dasabuvir taken orally BID as 3.08 mg mini-tablets based on body weight. Participants with HCV GT1a without cirrhosis received 12-week treatment with the mini-tablet 3-DAA regimen and ribavirin was provided as a 40 mg/mL oral solution and administered per local label.

Drug: Ombitasvir mini tablet; Drug: Paritaprevir mini tablet; Drug: Ritonavir mini tablet; Drug: Dasabuvir mini tablet; Drug: Ribavirin solution

Interventions

Ombitasvir/paritaprevir/ritonavir DRUG

Film-coated tablet for oral use

Also known as: Ombitasvir also known as ABT-267, Paritaprevir also known as ABT-450, Ombitsvir/paritaprevir/ritonavir also known as Viekirax

Adult tablet, 12-17 yr, Part 1; Adult tablet, 12-17 yr, Part 2

Dasabuvir DRUG

Film-coated tablet for oral use

Also known as: Exviera, ABT-333

Adult tablet, 12-17 yr, Part 1; Adult tablet, 12-17 yr, Part 2

Ribavirin DRUG

Film-coated tablet for oral use

Adult tablet, 12-17 yr, Part 1; Adult tablet, 12-17 yr, Part 2

Ombitasvir mini tablet DRUG

Film-coated tablet for oral use

Also known as: ABT-267

Mini tablet, 3-8 yr, Part 1; Mini tablet, 9-11 yr, Part 1

Paritaprevir mini tablet DRUG

Film-coated tablet for oral use

Also known as: ABT-450

Mini tablet, 3-8 yr, Part 1; Mini tablet, 9-11 yr, Part 1

Ritonavir mini tablet DRUG

Film-coated tablet for oral use

Mini tablet, 3-8 yr, Part 1; Mini tablet, 9-11 yr, Part 1

Dasabuvir mini tablet DRUG

Film-coated tablet for oral use

Also known as: Exviera, ABT-333

Mini tablet, 3-8 yr, Part 1; Mini tablet, 9-11 yr, Part 1

Ribavirin solution DRUG

Oral solution

Mini tablet, 3-8 yr, Part 1; Mini tablet, 9-11 yr, Part 1

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Positive anti-hepatitis C virus antibody (HCV Ab) and HCV ribonucleic acid (RNA) ≥ 1000 IU/mL at the time of screening
• HCV genotype 1 for enrollment into Part 1 of the study and genotype 1 or 4 for enrollment into Part 2
• 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

You may not qualify if:

• Female participant who is pregnant, breastfeeding or is considering becoming pregnant
• 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.
• Positive test result for Hepatitis B surface antigen (HbsAg) or anti-human immunodeficiency virus antibody (HIV Ab) test
• 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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (21)

UCSF Benioff Childrens Hosp /ID# 136774

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado /ID# 137017

Aurora, Colorado, 80045, United States

Location

University of Florida - Archer /ID# 136830

Gainesville, Florida, 32610, United States

Location

Advent Health /ID# 167663

Orlando, Florida, 32803, United States

Location

Indiana University /ID# 137015

Indianapolis, Indiana, 46202, United States

Location

Boston Childrens Hospital /ID# 137174

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center /ID# 136831

Boston, Massachusetts, 02118, United States

Location

Columbia Univ Medical Center /ID# 136431

New York, New York, 10032-3725, United States

Location

Children's Hospital of Philadelphia /ID# 137018

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine /ID# 136590

Houston, Texas, 77030-3411, United States

Location

Seattle Children's Hospital /ID# 137019

Seattle, Washington, 98105, United States

Location

Cliniques Universitaires Saint-Luc /ID# 136910

Brussels, Brussels Capital, 1200, Belgium

Location

UZ Leuven /ID# 136911

Leuven, 3000, Belgium

Location

Charite Universitaetsmedizin Berlin /ID# 141620

Berlin, 10117, Germany

Location

Universitaetsklinikum Freiburg /ID# 141618

Freiburg im Breisgau, 79106, Germany

Location

Helios Klinikum Wuppertal /ID# 142883

Wuppertal, 42283, Germany

Location

San Jorge Children Hospital /ID# 136832

San Juan, 00912-3310, Puerto Rico

Location

Hospital Sant Joan de Deu /ID# 137096

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Hospital Universitario Vall d'Hebron /ID# 137098

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz /ID# 137094

Madrid, 28046, Spain

Location

Hospital Universitario y Politecnico La Fe /ID# 137097

Valencia, 46026, Spain

Location

Related Publications (1)

• 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.

  PMID: 32451952 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

ombitasvir; paritaprevir; dasabuvir; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

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

Study Record Dates

• First Submitted: June 17, 2015
• First Posted: July 1, 2015
• Study Start: October 28, 2015
• Primary Completion: November 19, 2020
• Study Completion: November 19, 2020
• Last Updated: October 5, 2021
• Results First Posted: October 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• 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 (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.

Locations

US (11); ES (4); PR (1); BE (2); DE (3)