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
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C
Hepatitis C Virus (HCV) Infection
Drug: ABT-267
Drug: Pegylated interferon (pegIFN)
Drug: Ribavirin (RBV)
Other: Placebo for ABT-267
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Enrollment: 37
Study Start Date: March 2011
Study Completion Date: February 2013
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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
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.
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
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.
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.

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01314261

Locations
United States, Alabama
Site Reference ID/Investigator# 56623
Birmingham, Alabama, United States, 35215
United States, California
Site Reference ID/Investigator# 48476
Los Angeles, California, United States, 90048
United States, Florida
Site Reference ID/Investigator# 51345
Orlando, Florida, United States, 32809
United States, Hawaii
Site Reference ID/Investigator# 51498
Honolulu, Hawaii, United States, 96814
United States, Indiana
Site Reference ID/Investigator# 48473
Indianapolis, Indiana, United States, 46202
United States, Missouri
Site Reference ID/Investigator# 52782
Kansas City, Missouri, United States, 64131
United States, Texas
Site Reference ID/Investigator# 48471
Houston, Texas, United States, 77030
Site Reference ID/Investigator# 48474
San Antonio, Texas, United States, 78215
United States, Virginia
Site Reference ID/Investigator# 48477
Fairfax, Virginia, United States, 22031
United States, Washington
Site Reference ID/Investigator# 48472
Seattle, Washington, United States, 98101
Puerto Rico
Site Reference ID/Investigator# 48483
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Armen Asatryan, MD AbbVie
  More Information

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01314261     History of Changes
Other Study ID Numbers: M12-114
Study First Received: March 11, 2011
Results First Received: December 29, 2014
Last Updated: January 21, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis A
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferons
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 01, 2015