Study of ABT-267 in Treatment Naive Hepatitis C Virus (HCV) Genotype 1 Infected Subjects

AbbVie (prior sponsor, Abbott)37 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Chronic Hepatitis C Hepatitis C Virus (HCV) Infection

Interventions

ABT-267DRUG

5 mg or 25 mg tablets

Pegylated interferon (pegIFN)DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly

Ribavirin (RBV)DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (11)

Site Reference ID/Investigator# 56623

Birmingham, Alabama, United States

Site Reference ID/Investigator# 48476

Los Angeles, California, United States

Site Reference ID/Investigator# 51345

Orlando, Florida, United States

Outcomes

Primary Outcomes

Percentage of Participants With 4-week Rapid Virologic Response (RVR)

Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Rapid virologic response was defined as HCV RNA levels \< the lower limit of detection (\< 15 IU/mL) at Week 4. Data are reported as percentage of participants with RVR.

Time frame: Week 4

Maximum Plasma Concentration (Cmax) of ABT-267

Blood samples were collected 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). The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the plasma after administration in a dosing interval. The Cmax of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

Time frame: 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)

Time to Maximum Plasma Concentration (Tmax) of ABT-267

Blood samples were collected 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). The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

Time frame: 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)

Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-267

Blood samples were collected 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. The samples were analyzed for the concentration of ABT-267 using validated analytical methods. The area under the plasma concentration -time curve (AUC; measured in ng\*hr/mL) is a method of measurement of the total exposure of a drug in blood plasma. The AUC24 of ABT-267 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

Data from ClinicalTrials.gov

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Secondary Outcomes

Percentage of Participants With Partial Early Virologic Response (pEVR)

Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Partial EVR was defined as HCV RNA levels that decreased \> 2 log10 IU/mL at Week 12 as compared to baseline HCV RNA levels. Data are reported as the percentage of participants with pEVR.

Time frame: Baseline and Week 12

Percentage of Participants With Complete Early Virologic Response (cEVR)

Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Complete EVR was defined as HCV RNA \< the lower limit of quantification (\< 25 IU/mL) at Week 12. Data are reported as the percentage of participants with cEVR.

Time frame: Week 12

Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing

Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Sustained virologic response was defined as HCV RNA levels \< the lower limit of quantification (\< 25 IU/mL) 12 weeks after the last dose of pegIFN/RBV. Data are reported as the percentage of participants with SVR12.

Time frame: 12 weeks after the last dose of pegIFN/RBV

Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing

Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Sustained virologic response was defined as HCV RNA levels \< the lower limit of quantification (\< 25 IU/mL) 24 weeks after the last dose of pegIFN/RBV. Data are reported as the percentage of participants with SVR24.

Time frame: 24 weeks after the last dose of pegIFN/RBV

Median Time to Suppression of Hepatitis C Virus Ribonucleic Acid (HCV RNA)

Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Time to suppression was defined as the time (measured in days) to HCV RNA levels \< the lower limit of quantification (\< 25 IU/mL). Data are reported as the median number of days.

Time frame: Approximately 12 weeks

Percentage of Participants With Extended Rapid Virologic Response (eRVR)

Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Extended RVR was defined as HCV RNA levels \< the lower level of quantification (\< 25 IU/mL) at Weeks 4 through 12. Data are reported as the percentage of participants with eRVR.

Time frame: Week 4 through Week 12