A Study to Evaluate the Safety and Effect of Co-administration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection

Hepatitis C, Chronic Clinical Trial

— PEARL-I  

Official title:

A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Coadministration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection (PEARL-I)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01685203
• Other study ID #: M13-393
• Secondary ID: 2011-005762-38
• Status: Completed
• Phase: Phase 2
• Start date: August 2012
• Est. completion date: February 2015

Study information

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

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of co-administration of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adults with chronic hepatitis C virus infection.

Description:

This was a Phase 2, randomized, open-label, combination treatment study of the 2-DAA regimen (ABT-450 150 mg QD + ritonavir 100 mg QD + ABT-267 25 mg QD) in adult HCV GT1b-infected treatment-naïve and Pegylated-interferon/ribavirin (pegIFN/RBV) treatment-experienced participants without cirrhosis and with compensated cirrhosis, and in adult GT4-infected treatment-naïve and pegIFN/RBV treatment-experienced participants without cirrhosis. Treatment Group 5 was not open to enrollment, based on a protocol-specified interim review of results from the treatment-naïve GT4 Groups 1 and 4 that indicated higher sustained virologic response (SVR) rates among participants receiving the 2-DAA regimen with RBV. All other groups completed the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 316
• Est. completion date: February 2015
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile

• Subjects must meet one of the following:

• Treatment-naive: Subject has never received antiviral treatment for hepatitis C infection OR

• Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegIFN/RBV);

• Body mass index (BMI) is = 18 to < 38 kg/m^2.

• Chronic HCV genotype 1b infection/with or without cirrhosis or HCV genotype 4 infection/without cirrhosis for at least 6 months prior to study screening.

• Subject has plasma HCV RNA level > 10,000 IU/mL at Screening

Exclusion Criteria:

• History of severe, life-threatening or other significant sensitivity to any drug.

• Females who were pregnant or planned to become pregnant, or breastfeeding, or GT4-infected males whose partners were pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug/RBV.

• Recent history of drug or alcohol abuse that could preclude adherence to the protocol.

• Positive test result for hepatitis B surface antigen or anti-Human Immunodeficiency Virus (HIV) antibodies.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Virus Diseases

Intervention

Drug:
• ABT-450/r
Tablet; ABT-450; Capsule; ritonavir
• ABT-267
Tablet
• Ribavirin (RBV)
Tablet

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

References & Publications (2)

Hézode C, Asselah T, Reddy KR, Hassanein T, Berenguer M, Fleischer-Stepniewska K, Marcellin P, Hall C, Schnell G, Pilot-Matias T, Mobashery N, Redman R, Vilchez RA, Pol S. Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial. Lancet. 2015 Jun 20;385(9986):2502-9. doi: 10.1016/S0140-6736(15)60159-3. Epub 2015 Mar 31. — View Citation

Lawitz E, Makara M, Akarca US, Thuluvath PJ, Preotescu LL, Varunok P, Morillas RM, Hall C, Mobashery N, Redman R, Pilot-Matias T, Vilchez RA, Hézode C. Efficacy and Safety of Ombitasvir, Paritaprevir, and Ritonavir in an Open-Label Study of Patients With Genotype 1b Chronic Hepatitis C Virus Infection With and Without Cirrhosis. Gastroenterology. 2015 Oct;149(4):971-80.e1. doi: 10.1053/j.gastro.2015.07.001. Epub 2015 Jul 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment	The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [	12 weeks after the last actual dose of study drug
Secondary	Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment	The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [	24 weeks after the last actual dose of study drug
Secondary	Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure.	Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [= LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment), or fail to suppress (HCV RNA = LLOQ persistently during treatment with at least 6 weeks [= 36 days] of treatment).	Baseline (Day 1), Day 3, and Treatment Weeks 1, 2 ,3 ,4, 6, 8, 10, and 12 for all participants and Treatment Weeks 16, 20 and 24 for Groups 7 and 8
Secondary	Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse.	Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) = 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 with HCV RNA < LLOQ at the end of treatment.	Within 12 weeks after the last dose of study drug
Secondary	Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events	Treatment-emergent adverse events were defined as any event that began or worsened in severity after initiation of study drug through 30 days after the last dose of study drug.	From the start of study drug administration until 30 days after the last dose,16 weeks for Groups 1, 2, 3, 4, and 6, and 28 weeks for Groups 7 and 8.

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