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)

• 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: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: February 24, 2017
• First Posted Date: March 1, 2017
• Results First Submitted Date: May 14, 2021
• Results First Posted Date: July 13, 2021
• Last Update Posted Date: September 30, 2022
• Actual Study Start Date: March 20, 2017
• Actual Primary Completion Date: May 21, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 14, 2021)

• 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.
• 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.
• 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.

Original Primary Outcome Measures (submitted: February 24, 2017)

• Area under the curve (AUC) of Glecaprevir (GLE) [ Time Frame: Up to 16 weeks ]
  The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma.
• AUC of Pibrentasvir (PIB) [ Time Frame: Up to 16 weeks ]
  The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in blood plasma.

Current Secondary Outcome Measures (submitted: May 14, 2021)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: February 24, 2017)

• Maximum observed plasma concentration (Cmax) of GLE [ Time Frame: Up to 16 weeks ]
  Maximum observed plasma concentration (Cmax) of GLE after administration.
• Maximum observed plasma concentration (Cmax) of PIB [ Time Frame: Up to 16 weeks ]
  Maximum observed plasma concentration (Cmax) of PIB after administration.
• Clearance of GLE [ Time Frame: Up to 16 weeks ]
  Clearance is defined the volume of plasma cleared of the drug per unit time.
• Clearance of PIB [ Time Frame: Up to 16 weeks ]
  Clearance is defined the volume of plasma cleared of the drug per unit time.
• Percentage of participants with sustained virologic response 12 weeks post dosing (SVR12) [ Time Frame: 12 weeks after last dose of study drug ]
  SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) levels less than the lower limit of quantitation (LLOQ) (less than 15 IU/mL) 12 weeks after the last actual dose of study drug.
• Percentage of participants who with post-treatment HCV virologic relapse [ Time Frame: Up to 160 weeks after first dose of study drug ]
  Post-treatment relapse is defined as confirmed HCV RNA greater than or equal to the LLOQ between end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA less than LLOQ at the end of treatment; excluding participants who have been shown to be re-infected.
• Percentage of participants who experience on-treatment virologic failure (i.e., breakthrough or fail to suppress) [ Time Frame: Up to 160 weeks after first dose of study drug ]
  Virologic failure defined as confirmed increase of greater than 1 log10 IU/mL above nadir during treatment, confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA less than LLOQ during treatment, or HCV RNA greater than or equal to LLOQ at the end of treatment with at least 6 weeks of treatment.
• Percentage of participants with new HCV infection at any time up to the last study visit [ Time Frame: Up to 160 weeks after first dose of study drug ]
  Participants with new HCV infection at any time up to the last study visit.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatitis C Virus (HCV)

Intervention

• Drug: Glecaprevir/pibrentasvir adult formulation
  Film-coated tablet (100 mg/40 mg)
  Other Name: ABT-493/ABT-530
• Drug: Glecaprevir/pibrentasvir pediatric formulation
  Film-coated pellets/granules (15.67%/8.25%)
  Other Name: ABT-493/ABT-530

Study Arms

• 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
  Intervention: Drug: Glecaprevir/pibrentasvir adult formulation
• 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
  Intervention: Drug: Glecaprevir/pibrentasvir pediatric formulation
• 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
  Intervention: Drug: Glecaprevir/pibrentasvir pediatric formulation
• 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
  Intervention: Drug: Glecaprevir/pibrentasvir pediatric formulation

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 14, 2021): 127
• Original Estimated Enrollment (submitted: February 24, 2017): 100
• Actual Study Completion Date: September 15, 2022
• Actual Primary Completion Date: May 21, 2020 (Final data collection date for primary outcome measure)

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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Germany, Japan, Puerto Rico, Russian Federation, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03067129
• Other Study ID Numbers: M16-123; 2016-004102-34 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: 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/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: September 2022