Clinical trial NCT01563536: Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
Official title: An Open-Label, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C Infection
Keywords: Hepatitis C,Genotype 1
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2012-03-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and antiviral activity of multiple, ascending doses of ABT-267 (also known as ombitasvir) administered as two-day monotherapy followed by ABT-267 in combination therapy with other direct-acting antiviral agents (DAAs) ABT-450 with ritonavir (ABT-450/r) and ABT-333 (also known as dasabuvir) plus ribavirin (RBV) in patients with chronic Hepatitis C virus (HCV) infection without cirrhosis.

Detailed description: An open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of ABT-267 as monotherapy for 2 days, followed by ABT-267, ABT-450 with ritonavir (ABT-450/r) and ABT-333 plus ribavirin (RBV) combination therapy for 12 weeks in treatment-naïve, non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. The study included post-treatment follow-up for 48 weeks.

Eligibility criteria: Inclusion Criteria:

* Male or female between the age of 18 and 70 years, inclusive, at time of enrollment.
* Subject has never received antiviral treatment for hepatitis C virus (HCV) infection.
* Body mass index (BMI) is ≥ 18 to \< 38 kg/m\^2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
* Chronic HCV genotype 1-infection for at least 6 months prior to study enrollment.
* 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 are or plan to become pregnant or breastfeeding or males whose partner is pregnant or planning to become pregnant.
* 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.
* Any current or past clinical evidence of cirrhosis (e.g., ascites, esophageal varices), or a liver biopsy or FibroTest/aspartate aminotransferase to platelet ratio (APRI) or FibroScan® showing cirrhosis or extensive bridging fibrosis.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1
timeFrame: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
measure: Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1
timeFrame: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1
timeFrame: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
measure: Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3
timeFrame: Day 2 (pre-dose) and Day 3 (pre-dose)
measure: Number of Participants With Adverse Events (AEs)
timeFrame: All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks).
measure: Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy
timeFrame: Pre-dose on Days 1, 2, and 3
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy
timeFrame: 12 and 24 weeks after last dose of combination study drug
measure: Percentage of Participants With Rapid Virologic Response
timeFrame: 4 weeks
measure: Percentage of Participants With End-of-Treatment Response
timeFrame: 12 weeks
measure: Percentage of Participants With Extended Rapid Virologic Response
timeFrame: Weeks 4 to 12
measure: Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy
timeFrame: Predose on Days 1, 2, and 3
Other outcomes:
measure: Resistance-Associated Variants and Phenotypic Resistance
timeFrame: Day 1 Pre-dose (Baseline) and Day 3 Pre-dose
Locations:
city: Bakersfield
country: United States
facility: Site Reference ID/Investigator# 68002
state: California
city: Orlando
country: United States
facility: Site Reference ID/Investigator# 67383
state: Florida
city: Annapolis
country: United States
facility: Site Reference ID/Investigator# 67382
state: Maryland
city: Poughkeepsie
country: United States
facility: Site Reference ID/Investigator# 67385
state: New York
Study officials:
affiliation: AbbVie
name: Andrew L Campbell, MD
role: STUDY_DIRECTOR
References:
citation: Mensing S, Polepally AR, Konig D, Khatri A, Liu W, Podsadecki TJ, Awni WM, Menon RM, Dutta S. Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Patients with Hepatitis C Virus Genotype 1 Infection: Combined Analysis from 9 Phase 1b/2 Studies. AAPS J. 2016 Jan;18(1):270-80. doi: 10.1208/s12248-015-9846-1. Epub 2015 Nov 23.