Clinical trial NCT01314261: Study of ABT-267 in Treatment Naive Hepatitis C Virus (HCV) Genotype 1 Infected Subjects
Official title: A Blinded, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Pharmacokinetics, and Antiviral Activity of ABT-267 in Combination With Peginterferon Alpha-2a and Ribavirin (pegIFN/RBV) in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C
Hepatitis C Virus (HCV) Infection
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2011-03-14
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
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, pharmacokinetics, and 4-week rapid virologic response (RVR) of 3 different doses of ABT-267 (also known as ombitasvir) in combination with pegylated interferon/ribavirin (pegIFN/RBV) compared with pegIFN/RBV alone (ABT-267 placebo) in treatment naïve, hepatitis C virus (HCV), genotype 1-infected participants.

Detailed description: The study was a randomized, double blind, placebo controlled study consisting of 2 substudies. In substudy 1, participants received 1 of 3 doses of ABT-267 or placebo + pegIFN/RBV for 12 weeks. In substudy 2, participants received pegIFN/RBV for 36 weeks. Participants were followed for 48 weeks post ABT-267 treatment for evaluation of efficacy and safety.

Eligibility criteria: Inclusion Criteria:

* Treatment naïve participants
* Females must be either postmenopausal for at least 2 years or surgically sterile
* Males must be surgically sterile or practicing specific forms of birth control
* Chronic hepatitis C virus (HCV), genotype-1 infected participants
* Documented FibroTest score in combination with an Aspartate Aminotransferase to Platelet Ratio Index (APRI), or a liver biopsy within the last 12 months to document absence of cirrhosis

Exclusion Criteria:

* Pregnant or breastfeeding female
* Use of any medications contraindicated for use with pegylated interferon(pegIFN) or ribavirin (RBV) 2 weeks prior to study drug administration or 10 half-lives, whichever is longer
* Clinically significant cardiac, respiratory (except mild asthma), renal, gastrointestinal, hematologic, neurologic disease, or any uncontrolled medical illness or psychiatric disease or disorder
* Current or past clinical evidence of cirrhosis or bridging fibrosis
* Abnormal screening laboratory results

Primary outcomes:
measure: Percentage of Participants With 4-week Rapid Virologic Response (RVR)
timeFrame: Week 4
measure: Maximum Plasma Concentration (Cmax) of ABT-267
timeFrame: Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
measure: Time to Maximum Plasma Concentration (Tmax) of ABT-267
timeFrame: Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
measure: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-267
timeFrame: Immediately prior to morning dose (time 0 hours); 2, 4, 6, and 8 hours after the morning dose on Day 1; prior to dose on Day 2 (24 hours after Day 1 dose); and at each subsequent study visit up to Week 12
measure: Plasma Concentrations of Ribavirin (RBV)
timeFrame: At each study visit from Week 1 to Week 12
measure: Serum Concentrations of Pegylated Interferon (pegIFN)
timeFrame: At each study visit from Week 1 to Week 12
Secondary outcomes:
measure: Percentage of Participants With Partial Early Virologic Response (pEVR)
timeFrame: Baseline and Week 12
measure: Percentage of Participants With Complete Early Virologic Response (cEVR)
timeFrame: Week 12
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing
timeFrame: 12 weeks after the last dose of pegIFN/RBV
measure: Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing
timeFrame: 24 weeks after the last dose of pegIFN/RBV
measure: Median Time to Suppression of Hepatitis C Virus Ribonucleic Acid (HCV RNA)
timeFrame: Approximately 12 weeks
measure: Percentage of Participants With Extended Rapid Virologic Response (eRVR)
timeFrame: Week 4 through Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Site Reference ID/Investigator# 56623
state: Alabama
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator# 48476
state: California
city: Orlando
country: United States
facility: Site Reference ID/Investigator# 51345
state: Florida
city: Honolulu
country: United States
facility: Site Reference ID/Investigator# 51498
state: Hawaii
city: Indianapolis
country: United States
facility: Site Reference ID/Investigator# 48473
state: Indiana
city: Kansas City
country: United States
facility: Site Reference ID/Investigator# 52782
state: Missouri
city: Houston
country: United States
facility: Site Reference ID/Investigator# 48471
state: Texas
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 48474
state: Texas
city: Fairfax
country: United States
facility: Site Reference ID/Investigator# 48477
state: Virginia
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 48472
state: Washington
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 48483
Study officials:
affiliation: AbbVie
name: Armen Asatryan, 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.