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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01314261
First received: March 11, 2011
Last updated: January 21, 2015
Last verified: January 2015

March 11, 2011
January 21, 2015
March 2011
January 2012   (final data collection date for primary outcome measure)
  • Percentage of Participants With 4-week Rapid Virologic Response (RVR) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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.
  • Maximum Plasma Concentration (Cmax) of ABT-267 [ 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) ] [ Designated as safety issue: No ]
    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 to Maximum Plasma Concentration (Tmax) of ABT-267 [ 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.
  • Plasma Concentrations of Ribavirin (RBV) [ Time Frame: At each study visit from Week 1 to Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: At each study visit from Week 1 to Week 12 ] [ Designated as safety issue: No ]
    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).
Assess 4-week rapid virologic response (RVR) [ Time Frame: At Week 4 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01314261 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Partial Early Virologic Response (pEVR) [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.
  • Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing [ Time Frame: 12 weeks after the last dose of pegIFN/RBV ] [ Designated as safety issue: No ]
    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 Sustained Virologic Response 24 Weeks (SVR24) Post-pegylated Interferon/Ribavirin (pegIFN/RBV) Dosing [ Time Frame: 24 weeks after the last dose of pegIFN/RBV ] [ Designated as safety issue: No ]
    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.
  • Median Time to Suppression of Hepatitis C Virus Ribonucleic Acid (HCV RNA) [ Time Frame: Approximately 12 weeks ] [ Designated as safety issue: No ]
    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 Extended Rapid Virologic Response (eRVR) [ Time Frame: Week 4 through Week 12 ] [ Designated as safety issue: No ]
    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.
  • Assess percentage of subjects with partial early virologic response (EVR). [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
  • Assess percentage of subjects with complete early virologic response (cEVR). [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of ABT-267 in Treatment Naive Hepatitis C Virus (HCV) Genotype 1 Infected Subjects
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
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.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Chronic Hepatitis C
  • Hepatitis C Virus (HCV) Infection
  • Drug: ABT-267
    5 mg or 25 mg tablets
    Other Name: Ombitasvir
  • Drug: Pegylated interferon (pegIFN)
    Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly
  • Drug: 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.
  • Experimental: ABT-267 (5 mg) once daily + pegIFN/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.
    Interventions:
    • Drug: ABT-267
    • Drug: Pegylated interferon (pegIFN)
    • Drug: Ribavirin (RBV)
  • Experimental: ABT-267 (50 mg) once daily + pegIFN/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.
    Interventions:
    • Drug: ABT-267
    • Drug: Pegylated interferon (pegIFN)
    • Drug: Ribavirin (RBV)
  • Experimental: ABT-267 (200 mg) once daily + pegIFN/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.
    Interventions:
    • Drug: ABT-267
    • Drug: Pegylated interferon (pegIFN)
    • Drug: Ribavirin (RBV)
  • Placebo Comparator: Placebo + pegIFN/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.
    Interventions:
    • Drug: Pegylated interferon (pegIFN)
    • Drug: Ribavirin (RBV)
    • Other: Placebo for ABT-267
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
37
February 2013
January 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT01314261
M12-114
No
Not Provided
Not Provided
AbbVie (prior sponsor, Abbott)
AbbVie (prior sponsor, Abbott)
Not Provided
Study Director: Armen Asatryan, MD AbbVie
AbbVie
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP