A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) When Given Together With ABT-333 and Ribavirin (RBV) in Treatment-Naïve and Non-responder Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Hepatitis C Clinical Trial

Official title:

An Open-Label Pilot Study to Evaluate the Antiviral Activity, Safety and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-333 and Ribavirin (RBV) in Treatment-Naive and Non-responder Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01306617
• Other study ID #: M12-746
• Status: Completed
• Phase: Phase 2
• First received: February 28, 2011
• Last updated: December 29, 2014
• Start date: February 2011
• Est. completion date: October 2012

Study information

• Verified date: December 2014
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the antiviral activity, safety, and pharmacokinetics of ABT-450 with ritonavir (ABT-450/r) dosed in combination with ABT-333 (also known as dasabuvir) and ribavirin (RBV) in treatment-naïve and non responder participants with genotype 1 chronic hepatitis C virus (HCV) infection.

Description:

This was a phase 2a multicenter, open-label, sequential, 3-arm, combination treatment study of a regimen of ABT-450/r/ABT-333, and ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected treatment-naïve participants and previous non-responders to pegylated interferon (pegIFN)/RBV treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: October 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Chronic hepatitis C virus (HCV)

• Treatment naive, null or partial responders to previous treatment with peginterferon and ribavirin

• Males and females 18-65 years old

• Body mass index 18 to < 35 kg/m^2

• Females must be postmenopausal for at least 2 years or surgically sterile

Exclusion Criteria:

• Cirrhosis or extensive bridging fibrosis

• History of cardiac disease

• Positive screen for certain drugs or alcohol

• Abnormal laboratory results

• Significant sensitivity to any drug

• Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody

• Use of strong cytochrome P450 3A (CYP3A), cytochrome P450 2C8 (CYP2C8), and organic anion transporting polypeptide 1B1 (OATP1B1) enzyme inducers or inhibitors within 1 month of dosing

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C Infection
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Infection

Intervention

Drug:
• ABT-450
tablets
• ABT-333
tablets
• ribavirin
tablets
• ritonavir
capsules

Locations

Country	Name	City	State
United States	Site Reference ID/Investigator# 48264	Aurora	Colorado
United States	Site Reference ID/Investigator# 51282	Gainesville	Florida
United States	Site Reference ID/Investigator# 50423	Kansas City	Missouri
United States	Site Reference ID/Investigator# 48263	Los Angeles	California
United States	Site Reference ID/Investigator# 50424	Madison	Wisconsin
United States	Site Reference ID/Investigator# 48268	New York	New York
United States	Site Reference ID/Investigator# 50427	Newport News	Virginia
United States	Site Reference ID/Investigator# 48266	San Antonio	Texas
United States	Site Reference ID/Investigator# 48265	Seattle	Washington
United States	Site Reference ID/Investigator# 50425	Springfield	Massachusetts
United States	Site Reference ID/Investigator# 50428	Statesville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Detection (LLOD) From Week 4 Through Week 12	Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of detection (< 15 IU/mL).	Week 4 through Week 12	No
Secondary	Percentage of Participants With HCV RNA < 1000 International Units Per Milliliter (IU/mL)	Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2.	Week 2	No
Secondary	Percentage of Participants With HCV RNA Below the Lower Limit of Quantitation (LLOQ; <25 IU/mL) at Week 4	Analysis of percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL).	Week 4	No
Secondary	Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment	Sustained virologic response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; < 25 IU/mL) 12 weeks after the last dose of study drug.	Post-treatment Day 1 to Post-treatment Week 12	No
Secondary	Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment	Sustained virologic response 24 (SVR24) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; < 25 IU/mL) 24 weeks after the last dose of study drug.	Post-treatment Day 1 to Post-treatment Week 24	No
Secondary	Time to Failure to Suppress or Rebound During Treatment	Time to failure to achieve a 2 log10 IU/mL HCV RNA decrease at Week 1, failure to achieve HCV RNA < Lower Limit of Detection (LLOD) at Week 6, or a confirmed increase of at least 0.5 log10 IU/mL above nadir (local minimum value) or confirmed HCV RNA > lower limit of quantitation (LLOQ) for participants who previously achieved HCV RNA < LLOQ.	Day 1 through Week 12	No
Secondary	Time to Virologic Relapse Post-treatment	Time to the first of 2 consecutive measurements of confirmed HCV RNA = lower limit of quantitation (LLOQ) at any point in the post-treatment period among participants with HCV RNA < LLOQ at the end of treatment.	Post-treatment Day 1 to post-treatment week 48	No
Secondary	Resistance-Associated Variants and Phenotypic Resistance	Baseline samples were analyzed for resistance-associated amino acid variants using population sequencing. Phenotypic resistance to ABT-450 or ABT-333 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Participants not achieving SVR12 were analyzed for resistance-associated variants at the time of failure using population sequencing and were compared with the baseline and appropriate reference sequences to assess amino acid changes. Phenotypic resistance to ABT-450 or ABT-333 at the time of failure was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance at baseline and at the time of failure are presented.	Day 1 to post-treatment week 48	No
Secondary	Pharmacokinetics (C Trough) of ABT 450 in HCV Infected Participants	Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.	Day 1 to Week 12	No
Secondary	Pharmacokinetics (C Trough) of ABT-333 in HCV Infected Participants	Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.	Day 1 to Week 12	No
Secondary	Pharmacokinetics (C Trough) of Ritonavir in HCV Infected Participants	Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.	Day 1 to Week 12	No
Secondary	Pharmacokinetics (C Trough) of Ribavirin in HCV Infected Participants	Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.	Day 1 to Week 12	No

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