We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03067129
Recruitment Status : Completed
First Posted : March 1, 2017
Results First Posted : July 13, 2021
Last Update Posted : September 30, 2022
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:

This is a Phase 2/3, open-label, multicenter study to evaluate the pharmacokinetics, efficacy,and safety of glecaprevir (GLE)/pibrentasvir (PIB) 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 were 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, who received the pediatric formulation of GLE + PIB.

Interim data are presented for all participants in Parts 1 and 2 who completed post-treatment Week 12 or prematurely discontinued from the study.


Condition or disease Intervention/treatment Phase
Hepatitis C Virus (HCV) Drug: Glecaprevir/pibrentasvir adult formulation Drug: Glecaprevir/pibrentasvir pediatric formulation Phase 2 Phase 3

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 127 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 20, 2017
Actual Primary Completion Date : May 21, 2020
Actual Study Completion Date : September 15, 2022


Arm Intervention/treatment
Experimental: Cohort 1: Adult formulation GLE/PIB, participants 12 to < 18 yrs
Adult formulation of glecaprevir (GLE)/pibrentasvir (PIB) 300 mg/120 mg co-formulated film-coated tablets once daily (QD) by mouth for 8, 12, or 16 weeks depending on hepatitis C virus (HCV) genotype, cirrhosis status, and prior treatment experience in participants 12 to < 18 years of age
Drug: Glecaprevir/pibrentasvir adult formulation
Film-coated tablet (100 mg/40 mg)
Other Name: ABT-493/ABT-530

Experimental: Cohort 2: Pediatric formulation GLE/PIB, participants 9 to < 12 yrs
Pediatric formulation of separate glecaprevir (GLE)/pibrentasvir (PIB)15.67% and 8.25% film-coated pellets/granules dosed based on body weight/age once daily (QD) by mouth for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience in participants 9 to < 12 years of age
Drug: Glecaprevir/pibrentasvir pediatric formulation
Film-coated pellets/granules (15.67%/8.25%)
Other Name: ABT-493/ABT-530

Experimental: Cohort 3: Pediatric formulation GLE/PIB, participants 6 to < 9 yrs
Pediatric formulation of separate glecaprevir (GLE)/pibrentasvir (PIB)15.67% and 8.25% film-coated pellets/granules dosed based on body weight/age once daily (QD) by mouth for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience in participants 6 to < 9 years of age
Drug: Glecaprevir/pibrentasvir pediatric formulation
Film-coated pellets/granules (15.67%/8.25%)
Other Name: ABT-493/ABT-530

Experimental: Cohort 4: Pediatric formulation GLE/PIB, participants 3 to < 6 yrs
Pediatric formulation of separate glecaprevir (GLE)/pibrentasvir (PIB)15.67% and 8.25% film-coated pellets/granules dosed based on body weight/age once daily (QD) by mouth for 8, 12, or 16 weeks depending on HCV genotype, cirrhosis status, and prior treatment experience in participants 3 to < 6 years of age
Drug: Glecaprevir/pibrentasvir pediatric formulation
Film-coated pellets/granules (15.67%/8.25%)
Other Name: ABT-493/ABT-530




Primary Outcome Measures :
  1. Steady-state Area Under the Plasma Concentration-time Curve (AUC) of Glecaprevir (GLE) at Week 2 [ Time Frame: At Week 2 ]
    AUC is a measure of how long and how much drug is present in the body after dosing. The amount of glecaprevir present was measured up to 24 hours after dosing and estimated using non-compartmental analysis.

  2. Steady-state Area Under the Plasma Concentration-time Curve (AUC) of Pibrentasvir (PIB) at Week 2 [ Time Frame: At Week 2 ]
    AUC is a measure of how long and how much drug is present in the body after dosing. The amount of pibrentasvir present was measured up to 24 hours after dosing and estimated using non-compartmental analysis.

  3. Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) [ Time Frame: 12 weeks after last dose of study drug (Week 20, 24, or 28 depending on treatment duration) ]
    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.


Secondary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) of Glecaprevir (GLE) at Week 2 [ Time Frame: At Week 2 ]
    Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administered and before administration of a second dose. It was estimated by non-compartmental pharmacokinetic analysis.

  2. Clearance (CL) of Glecaprevir (GLE) From Plasma at Week 2 [ Time Frame: At Week 2 ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body. It was estimated by non-compartmental pharmacokinetic analysis.

  3. Maximum Plasma Concentration (Cmax) of Pibrentasvir (PIB) at Week 2 [ Time Frame: At Week 2 ]
    Cmax is the peak concentration that a drug or drug metabolite achieves in a specified compartment after the drug has been administered and before administration of a second dose. It was estimated by non-compartmental pharmacokinetic analysis.

  4. Clearance (CL) of Pibrentasvir (PIB) From Plasma at Week 2 [ Time Frame: At Week 2 ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body. It was estimated by non-compartmental pharmacokinetic analysis.

  5. Percentage of Participants Who Experienced On-treatment Virologic Failure [ Time Frame: Up to Week 8, 12, or 16 (depending on treatment duration) ]
    On-treatment virologic failure is defined as hepatitis C virus ribonucleic acid (HCV RNA) confirmed increase of > 1 (subscript)10(subscript) IU/mL above nadir during treatment, confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < lower limit of quantification (LLOQ) during treatment, or HCV RNA ≥ LLOQ at the end of treatment with at least 6 weeks of treatment.

  6. Percentage of Participants With Post-treatment Relapse [ Time Frame: Up to 12 weeks after the last dose of study drug (Week 20, 24, or 28 depending on treatment duration) ]
    Post-treatment relapse is defined as confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ the lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA < LLOQ at the end of treatment; excluding participants who had been shown to be re-infected.

  7. Percentage of Participants With New Hepatitis C Virus (HCV) Infection (i.e., Reinfection) [ Time Frame: Up to 12 weeks after last dose of study drug (Week 20, 24, or 28 depending on treatment duration) ]
    Reinfection is defined as confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ the lower limit of quantification (LLOQ) in the post-treatment period along with post-treatment detection of a different HCV genotype, subtype, or clade compared with baseline.

  8. Palatability Questionnaire Question 1: How Convenient or Inconvenient Was it to Prepare the Dose? [ Time Frame: At the End of Treatment visit or at the premature discontinuation visit (up to 8, 12, or 16 weeks, depending on treatment duration) ]
    For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE/PIB formulation.

  9. Palatability Questionnaire Question 2: How Long Did it Typically Take for the Child to Take the Dose? [ Time Frame: At the End of Treatment visit or at the premature discontinuation visit (up to 8, 12, or 16 weeks, depending on treatment duration) ]
    For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE/PIB formulation.

  10. 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? [ Time Frame: At the End of Treatment visit or at the premature discontinuation visit (up to 8, 12, or 16 weeks, depending on treatment duration) ]
    For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE/PIB formulation.

  11. Palatability Questionnaire Question 4: Did You Experience Any Resistance When Feeding the Child the Medicine? [ Time Frame: At the End of Treatment visit or at the premature discontinuation visit (up to 8, 12, or 16 weeks, depending on treatment duration) ]
    For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE/PIB formulation.

  12. Palatability Questionnaire Question 4a: Type of Feeding Resistance [ Time Frame: At the End of Treatment visit or at the premature discontinuation visit (up to 8, 12, or 16 weeks, depending on treatment duration) ]
    For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE/PIB formulation.

  13. Palatability Questionnaire Question 5: How Easy or Difficult Was it for the Child to Swallow the Medicine? [ Time Frame: At the End of Treatment visit or at the premature discontinuation visit (up to 8, 12, or 16 weeks, depending on treatment duration) ]
    For each participant who received the pediatric formulation (Cohorts 2 - 4), the parent(s)/guardian(s) completed a Palatability Questionnaire to provide feedback on the perception of the dosage form. The Palatability Questionnaire included 6 questions related to the administration and ingestion of the pediatric GLE/PIB formulation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 IU/ mL

Exclusion Criteria:

  • Females who are pregnant or breastfeeding
  • Positive test result for Hepatitis B surface antigen (HbsAg) or positive test result for HBV 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03067129


Locations
Show Show 38 study locations
Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: AbbVie Inc. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] March 22, 2019
Statistical Analysis Plan  [PDF] January 24, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03067129    
Other Study ID Numbers: M16-123
2016-004102-34 ( EudraCT Number )
First Posted: March 1, 2017    Key Record Dates
Results First Posted: July 13, 2021
Last Update Posted: September 30, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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/
URL: https://vivli.org/ourmember/abbvie/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis, Chronic
Infections
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Flaviviridae Infections