Clinical trial NCT00851890: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
Official title: A Blinded, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C Virus Infection
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2009-02-26
Enrollment: 30
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 was to assess the safety, tolerability, pharmacokinetics and antiviral activity of ABT-333 (also known as dasabuvir) in treatment-naïve, hepatitis C virus (HCV)-infected participants.

Detailed description: This was a Phase 2a, blinded, randomized, placebo-controlled clinical trial in hepatitis C virus (HCV)-infected adults with 2 planned sequential evaluations, Part 1 and Part 2. The study evaluated the safety, tolerability, antiviral activity, and pharmacokinetics of ABT-333 or placebo monotherapy, followed by 26 days of ABT-333 or placebo with pegylated interferon a-2a (pegIFN) and ribavirin (RBV) combination therapy. Review of safety and efficacy in Part 1 of the study showed similar response rates across ABT-333 doses so Part 2 of the study was not performed. The study also assessed emergence of resistant HCV in conjunction with kinetics of viral load decay and rebound in treatment-naïve, HCV-infected participants.

Eligibility criteria: Inclusion Criteria:

* Participant has provided written consent.
* If female, participant is postmenopausal or surgically sterile.
* If male, must be practicing two effective methods of birth control.
* Participant is hepatitis C virus (HCV) genotype 1 with HCV ribonucleic acid levels \>50,000 IU/mL.
* Participants must demonstrate chronic hepatitis C infection for at least 6 months prior to study enrollment.
* Participants must have a liver biopsy with histology consistent with HCV-induced liver damage, and with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV.
* Condition of general good health other then HCV infection.
* Participants with a history of thyroid disease must have a thyroid stimulating hormone (TSH) value in the normal range.

Exclusion Criteria:

* No prior history of receiving therapy for HCV infection.
* Positive test result for hepatitis A virus immunoglobulin M (HAV-IgM), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus antibody (HIV Ab).
* Pregnant or breastfeeding females or male partners of women who are pregnant.
* History of seizures or cancer.
* History of major depressive disorder within 2 years.
* Any current or past history of cirrhosis.
* Any cause of liver disease other than chronic HCV infection.

Primary outcomes:
measure: Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Monotherapy Treatment
timeFrame: Prior to the first dose on Day 1 to before first dose on Day 3
measure: Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28
timeFrame: Prior to the first dose on Day 1 through Day 28
measure: Maximum Plasma Concentration (Cmax) of ABT-333
timeFrame: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2
measure: Time to Maximum Plasma Concentration (Tmax) of ABT-333
timeFrame: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2
measure: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC12) of ABT-333
timeFrame: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2
measure: Serum Concentrations of Pegylated Interferon (pegIFN)
timeFrame: Prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28
measure: Plasma Concentrations of Ribavirin (RBV)
timeFrame: Prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28
measure: Number of Participants Having Treatment-emergent Adverse Events (AEs)
timeFrame: AEs were collected from the time of study drug administration to 30 days after last dose of study drug (8 Weeks)
Secondary outcomes:
measure: Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28 or Final Visit
timeFrame: Day 28 and Final Visit
measure: Percentage of Participants With at Least a 2 log10 Maximal Decrease in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Treatment
timeFrame: Prior to the first dose on Day 1 and Day 28
measure: Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 25 IU/mL (the Lower Limit of Quantitation [LLOQ]) at Day 28 or Final Visit
timeFrame: Day 28 or Final Visit
measure: Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 10 IU/mL (Lower Limit of Detection [LLOD]) at Day 28 or Final Visit
timeFrame: Day 28 or Final Visit
measure: Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28
timeFrame: Days 1, 5, 10, 17, 24 and 28
measure: Number of Participants With Maximal Phenotypic Resistance to ABT-333 >10 Fold Relative to Baseline Through Day 28
timeFrame: Days 1 through 28
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Site Reference ID/Investigator# 16103
state: California
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator# 16124
state: California
city: Orlando
country: United States
facility: Site Reference ID/Investigator# 16102
state: Florida
city: Baton Rouge
country: United States
facility: Site Reference ID/Investigator# 16105
state: Louisiana
city: Chapel Hill
country: United States
facility: Site Reference ID/Investigator# 16106
state: North Carolina
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 16107
state: Texas
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 16123
state: Texas
city: Santurce
country: Puerto Rico
facility: Site Reference ID/Investigator# 16182
Study officials:
affiliation: AbbVie
name: Daniel Cohen, 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.