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

Chronic Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01314261
• Other study ID #: M12-114
• Status: Completed
• Phase: Phase 2
• Start date: March 2011
• Est. completion date: February 2013

Study information

• Verified date: January 2015
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: February 2013
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus (HCV) Infection
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Infection

Intervention

Drug:
• ABT-267
5 mg or 25 mg tablets
• Pegylated interferon (pegIFN)
Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly
• Ribavirin (RBV)
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

Other:
• Placebo for ABT-267
Participants received matching placebo tablet at each dose level for ABT-267.

Locations

Country	Name	City	State
Puerto Rico	Site Reference ID/Investigator# 48483	San Juan
United States	Site Reference ID/Investigator# 56623	Birmingham	Alabama
United States	Site Reference ID/Investigator# 48477	Fairfax	Virginia
United States	Site Reference ID/Investigator# 51498	Honolulu	Hawaii
United States	Site Reference ID/Investigator# 48471	Houston	Texas
United States	Site Reference ID/Investigator# 48473	Indianapolis	Indiana
United States	Site Reference ID/Investigator# 52782	Kansas City	Missouri
United States	Site Reference ID/Investigator# 48476	Los Angeles	California
United States	Site Reference ID/Investigator# 51345	Orlando	Florida
United States	Site Reference ID/Investigator# 48474	San Antonio	Texas
United States	Site Reference ID/Investigator# 48472	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

Mensing S, Polepally AR, König 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 4
Primary	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.	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)
Primary	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.	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)
Primary	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.	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
Primary	Plasma Concentrations of Ribavirin (RBV)	Blood samples were collected at each study visit from Week 1 to Week 12. The samples were analyzed for the concentration of RBV (measured in ng/mL) using validated analytical methods and RBV concentrations in plasma were summarized at each visit. Data are reported as the median (range).	At each study visit from Week 1 to Week 12
Primary	Serum Concentrations of Pegylated Interferon (pegIFN)	Blood samples were collected at each study visit from Week 1 to Week 12. The samples were analyzed for the concentration of pegIFN (measured in ng/mL) using validated analytical methods and pegIFN concentrations in serum were summarized at each visit. Data are reported as the median (range).	At each study visit from Week 1 to Week 12
Secondary	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.	Baseline and Week 12
Secondary	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.	Week 12
Secondary	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.	12 weeks after the last dose of pegIFN/RBV
Secondary	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.	24 weeks after the last dose of pegIFN/RBV
Secondary	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.	Approximately 12 weeks
Secondary	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.	Week 4 through Week 12

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