A Study to Evaluate Treatment of Hepatitis C Virus Infection in Pediatric Subjects (ZIRCON)
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| ClinicalTrials.gov Identifier: NCT02486406 |
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Recruitment Status :
Completed
First Posted : July 1, 2015
Results First Posted : October 5, 2021
Last Update Posted : October 5, 2021
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Sponsor:
AbbVie
Information provided by (Responsible Party):
AbbVie
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Hepatitis C Infection | Drug: Ombitasvir/paritaprevir/ritonavir Drug: Dasabuvir Drug: Ribavirin Drug: Ombitasvir mini tablet Drug: Paritaprevir mini tablet Drug: Ritonavir mini tablet Drug: Dasabuvir mini tablet Drug: Ribavirin solution | Phase 2 Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 64 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 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) |
| Actual Study Start Date : | October 28, 2015 |
| Actual Primary Completion Date : | November 19, 2020 |
| Actual Study Completion Date : | November 19, 2020 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Adult tablet, 12-17 yr, Part 1
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.
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Drug: Ombitasvir/paritaprevir/ritonavir
Film-coated tablet for oral use
Other Names:
Drug: Dasabuvir Film-coated tablet for oral use
Other Names:
Drug: Ribavirin Film-coated tablet for oral use |
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Experimental: Adult tablet, 12-17 yr, Part 2
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.
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Drug: Ombitasvir/paritaprevir/ritonavir
Film-coated tablet for oral use
Other Names:
Drug: Dasabuvir Film-coated tablet for oral use
Other Names:
Drug: Ribavirin Film-coated tablet for oral use |
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Experimental: Mini tablet, 9-11 yr, Part 1
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.
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Drug: Ombitasvir mini tablet
Film-coated tablet for oral use
Other Name: ABT-267 Drug: Paritaprevir mini tablet Film-coated tablet for oral use
Other Name: ABT-450 Drug: Ritonavir mini tablet Film-coated tablet for oral use Drug: Dasabuvir mini tablet Film-coated tablet for oral use
Other Names:
Drug: Ribavirin solution Oral solution |
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Experimental: Mini tablet, 3-8 yr, Part 1
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
Film-coated tablet for oral use
Other Name: ABT-267 Drug: Paritaprevir mini tablet Film-coated tablet for oral use
Other Name: ABT-450 Drug: Ritonavir mini tablet Film-coated tablet for oral use Drug: Dasabuvir mini tablet Film-coated tablet for oral use
Other Names:
Drug: Ribavirin solution Oral solution |
Primary Outcome Measures :
- Part 1: Maximum Plasma Concentration (Cmax) of Ombitasvir (OBV) [ 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 administrated and before administration of a second dose.
- Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ombitasvir (OBV) [ 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 ombitasvir present was measured up to 24 hours after dosing.
- Part 1: Lowest Plasma Concentration (Ctrough) of Ombitasvir (OBV) [ Time Frame: At Weeks 2 and 8 ]Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
- Part 1: Maximum Plasma Concentration (Cmax) of Paritaprevir (PTV) [ 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 administrated and before administration of a second dose.
- Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Paritaprevir (PTV) [ 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 paritaprevir present was measured up to 24 hours after dosing.
- Part 1: Lowest Plasma Concentration (Ctrough) of Paritaprevir (PTV) [ Time Frame: At Weeks 2 and 8 ]Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
- Part 1: Maximum Plasma Concentration (Cmax) of Dasabuvir (DSV) [ 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 administrated and before administration of a second dose.
- Part 1: Concentration of Drug in Blood Plasma Against Time [Area Under the Curve (AUC)] of Dasabuvir (DSV) [ 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 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.
- Part 1: Lowest Plasma Concentration (Ctrough) of Dasabuvir (DSV) [ Time Frame: At Weeks 2 and 8 ]Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
- Part 1: Maximum Plasma Concentration (Cmax) of Ritonavir (RTV) [ 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 administrated and before administration of a second dose.
- Part 1: Concentration of Drug in Blood Plasma Over Time [Area Under the Curve (AUC)] of Ritonavir (RTV) [ 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 ritonavir present was measured up to 24 hours after dosing.
- Part 1: Lowest Plasma Concentration (Ctrough) of Ritonavir (RTV) [ Time Frame: At Weeks 2 and 8 ]Minimum plasma concentration (Ctrough; measured in ng/mL) was directly determined from the concentration-time data.
- Parts 1 and 2: Percentage of Participants With Sustained Virologic Response 12 Weeks After the Last Actual Dose of Study Drug (SVR12) [ Time Frame: 12 weeks after last dose of study drug (Week 24 or 36 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 :
- 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 [ Time Frame: 12 weeks after last dose of study drug (Week 24 or 36 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.
- 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 [ Time Frame: 24 weeks after last dose of study drug (Week 36 or 48 depending on treatment duration) ]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.
- 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 [ Time Frame: 12 or 24 weeks after starting study drug, depending on treatment duration ]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.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 3 Years to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
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): NCT02486406
Locations
Show 21 study locations
Sponsors and Collaborators
AbbVie
Investigators
| Study Director: | AbbVie Inc. | AbbVie |
Study Documents (Full-Text)
Documents provided by AbbVie:
Documents provided by AbbVie:
Study Protocol [PDF] August 21, 2017
Statistical Analysis Plan [PDF] May 31, 2018
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT02486406 |
| Other Study ID Numbers: |
M14-748 2015-000111-41 ( EudraCT Number ) |
| First Posted: | July 1, 2015 Key Record Dates |
| Results First Posted: | October 5, 2021 |
| Last Update Posted: | October 5, 2021 |
| Last Verified: | September 2021 |
| 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: | 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. |
| URL: | https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html |
| 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:
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Hepatitis C Virus Hepatitis C Genotype 1 Hepatitis C Genotype 4 Pediatric |
Additional relevant MeSH terms:
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Infections Communicable Diseases Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic Disease Attributes Pathologic Processes Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections |
RNA Virus Infections Blood-Borne Infections Flaviviridae Infections Chronic Disease Ritonavir Ribavirin HIV Protease Inhibitors Viral Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |