Clinical trial NCT01685203: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C Virus
Ribavirin-Free
Hepatitis C Genotype 1
Hepatitis C
Interferon-Free
Chronic Hepatitis C
Compensated cirrhosis
Hepatitis C Genotype 4
Paritaprevir
Ombitasvir
Ritonavir
Ribavirin
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2012-09-14
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment
timeFrame: 12 weeks after the last actual dose of study drug
Secondary outcomes:
measure: Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment
timeFrame: 24 weeks after the last actual dose of study drug
measure: Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure.
timeFrame: 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
measure: Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse.
timeFrame: Within 12 weeks after the last dose of study drug
measure: Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events
timeFrame: 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.
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: Nilou Mobashery, MD
role: STUDY_DIRECTOR
References:
citation: Hezode 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.
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, Hezode 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.