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

Phase 2

Completed

Conditions: Chronic Hepatitis C
Hepatitis C Virus (HCV) Infection

Interventions: Drug: Pegylated interferon (pegIFN)
Drug: ABT-267
Drug: Ribavirin (RBV)
Other: Placebo for ABT-267

Registration Number: NCT01314261

Lead Sponsor: AbbVie (prior sponsor, Abbott)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ABT-267 (5 mg) once daily + pegIFN/RBV	Ribavirin (RBV)	Participants were given 5 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
ABT-267 (50 mg) once daily + pegIFN/RBV	Ribavirin (RBV)	Participants were given 50 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
ABT-267 (200 mg) once daily + pegIFN/RBV	Ribavirin (RBV)	Participants were given 200 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
Placebo + pegIFN/RBV	Pegylated interferon (pegIFN)	Participants were given matching placebo to ABT-267 once daily in combination with pegIFN/RBV for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
ABT-267 (5 mg) once daily + pegIFN/RBV	ABT-267	Participants were given 5 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
ABT-267 (5 mg) once daily + pegIFN/RBV	Pegylated interferon (pegIFN)	Participants were given 5 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
ABT-267 (50 mg) once daily + pegIFN/RBV	Pegylated interferon (pegIFN)	Participants were given 50 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
ABT-267 (50 mg) once daily + pegIFN/RBV	ABT-267	Participants were given 50 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
ABT-267 (200 mg) once daily + pegIFN/RBV	Pegylated interferon (pegIFN)	Participants were given 200 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
ABT-267 (200 mg) once daily + pegIFN/RBV	ABT-267	Participants were given 200 mg ABT-267 once daily in combination with pegylated interferon/ribavirin (pegIFN/RBV) for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
Placebo + pegIFN/RBV	Ribavirin (RBV)	Participants were given matching placebo to ABT-267 once daily in combination with pegIFN/RBV for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.
Placebo + pegIFN/RBV	Placebo for ABT-267	Participants were given matching placebo to ABT-267 once daily in combination with pegIFN/RBV for 12 weeks, followed by 36 weeks of pegIFN/RBV treatment alone. Pegylated interferon was dosed 180 µg subcutaneously once a week. Ribavirin was dosed 1000 or 1200 mg daily divided twice a day.

Primary Outcome Measures

Name	Time	Method
Time to Maximum Plasma Concentration (Tmax) of ABT-267	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)	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.
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-267	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	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.
Percentage of Participants With 4-week Rapid Virologic Response (RVR)	Week 4	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.
Plasma Concentrations of Ribavirin (RBV)	At each study visit from Week 1 to Week 12	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).
Serum Concentrations of Pegylated Interferon (pegIFN)	At each study visit from Week 1 to Week 12	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).
Maximum Plasma Concentration (Cmax) of ABT-267	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)	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Partial Early Virologic Response (pEVR)	Baseline and Week 12	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.
Percentage of Participants With Complete Early Virologic Response (cEVR)	Week 12	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.
Median Time to Suppression of Hepatitis C Virus Ribonucleic Acid (HCV RNA)	Approximately 12 weeks	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.
Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing	12 weeks after the last dose of pegIFN/RBV	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.
Percentage of Participants With Extended Rapid Virologic Response (eRVR)	Week 4 through Week 12	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.
Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing	24 weeks after the last dose of pegIFN/RBV	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.

Trial Locations

Locations (11): Site Reference ID/Investigator# 52782
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Kansas City, Missouri, United States
Site Reference ID/Investigator# 51498
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Honolulu, Hawaii, United States
Site Reference ID/Investigator# 48483
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San Juan, Puerto Rico
Site Reference ID/Investigator# 56623
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Birmingham, Alabama, United States
Site Reference ID/Investigator# 48476
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Los Angeles, California, United States
Site Reference ID/Investigator# 51345
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Orlando, Florida, United States
Site Reference ID/Investigator# 48473
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Indianapolis, Indiana, United States
Site Reference ID/Investigator# 48471
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Houston, Texas, United States
Site Reference ID/Investigator# 48474
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San Antonio, Texas, United States
Site Reference ID/Investigator# 48477
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Fairfax, Virginia, United States
Site Reference ID/Investigator# 48472
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Seattle, Washington, United States