A Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-072 and Ribavirin (RBV)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of ABT-450 with ritonavir (ABT-450/r) dosed in combination with ABT-072 and ribavirin (RBV) in treatment-naïve participants with genotype 1 chronic hepatitis C virus (HCV) infection.

Detailed Description
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This was a Phase 2a multicenter, open-label, single arm, combination treatment study of a regimen of ABT-450/r/ABT-072, and ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-(1a or 1b) infected treatment-naïve participants.

Official Title
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An Open-Label Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-072 and Ribavirin (RBV) in Treatment-Naive Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Conditions
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Hepatitis C, HCV, Chronic Hepatitis C Infection, Hepatitis C Genotype 1

Intervention / Treatment
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* Drug: ABT-450
* Drug: ABT-072
* Drug: Ribavirin
* Drug: Ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis C, genotype 1 infection with interleukin 28B (IL28B) rs12979860 genotype C/C. Liver biopsy within 3 years with histology consistent with hepatitis C virus (HCV) - induced liver damage, with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV. Treatment naïve male or female between the ages of 18 and 65. Females must be postmenopausal for at least 2 years or surgically sterile. Be in a condition of general good health, as perceived by the investigator, other than hepatitis C virus infection. Body mass index 18 to < 35 kg/m^2 . Exclusion Criteria: Significant sensitivity to any drug. Use of herbal supplements within 2 weeks prior to study drug dosing. Positive screen for certain drugs or alcohol. Positive hepatitis B surface antigen or anti-human immunodeficiency virus (HIV) 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. Prior treatment with any investigational or commercially available anti-hepatitis C virus agents. Abnormal laboratory tests. Cirrhosis or extensive bridging fibrosis. History of cardiac disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-450/r and ABT-072, plus ribavirin (RBV)<br>ABT-450/r (150/100 mg) once daily (QD) and ABT-072 (400 mg) QD plus weight-based RBV divided twice daily (BID) for 12 weeks. | Drug: ABT-450<br>* tablets<br>Drug: ABT-072<br>* tablets<br>Drug: Ribavirin<br>* tablets<br>Drug: Ritonavir<br>* capsules<br>* Other names: Norvir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Quantitation (LLOQ) From Week 4 Through Week 12 | Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (< 25 IU/mL). | Week 4 through Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) < 1000 International Units Per Milliliter (IU/mL) | Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2. | Week 2 | 
| Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Below the Lower Limit of Quantitation (LLOQ) 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 | 
| 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 | 
| 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 | 
| Time to Failure to Suppress or Rebound During Treatment | The time to failure to suppress was defined as first day a participant met any virologic stopping criteria during treatment. The virologic stopping criteria also includes failure to achieve a 2 log10 IU/mL decrease in HCV RNA by Week 1, failure to achieve HCV RNA <LLOQ by Week 6, or rebound, defined as first day of 2 consecutive increases of at least 0.5 log10 IU/mL above nadir (local minimum value) or confirmed HCV RNA > lower limit of detection (LLOD) for participants who previously achieved HCV RNA < LLOD. | Day 1 through Week 12 | 
| Time to Virologic Relapse Through 24 Weeks Post-treatment | Time to confirmed hepatitis C virus (HCV) ribonucleic acid (RNA) ≥ lower limit of quantitation (LLOQ) (2 consecutive measurements ≥ 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 24 |