A Randomized Study to Evaluate the Safety, Tolerability and Antiviral Activity of ABT-450, ABT-333 and ABT-072 - Full Text View

Purpose

A 12-week study of combination direct-acting antiviral agent (DAA) and pegIFN/RBV in subjects with chronic HCV.

Condition	Intervention	Phase
Hepatitis C HCV Chronic Hepatitis C Genotype 1	Drug: ABT-450 Drug: ABT-072 Drug: ABT-333 Drug: ritonavir Drug: pegIFN Drug: ribavirin Other: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Blinded, Randomized, Placebo-controlled, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-450 With Ritonavir (ABT-450/r), ABT-333 or ABT-072 Each Administered Alone and in Combination With Peginterferon α-2a and Ribavirin (PegIFN/RBV) in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Ritonavir

U.S. FDA Resources

Further study details as provided by AbbVie:

Primary Outcome Measures:

Efficacy endpoint of maximum decrease from baseline in log10 HCV RNA levels during ABT-450/r, ABT-333 or ABT-072 monotherapy treatment [ Time Frame: Baseline to Study Day 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percentage of subjects with RVR (HCV RNA level < 25 IU/mL) at Study Week 4. [ Time Frame: Baseline to Study Week 4 ] [ Designated as safety issue: No ]
Percentage of subjects with partial EVR (HCV RNA decrease > 2 log10 IU/mL) or with complete EVR (HCV RNA level < 25 IU/mL) at Study Week 12 or the last treatment visit with DAA. [ Time Frame: Baseline to Study Week 12 ] [ Designated as safety issue: No ]

Enrollment:	74
Study Start Date:	March 2010
Study Completion Date:	January 2012
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 8. ABT-333 Groups 7-8 ABT-333 or matching placebo monotherapy for 3 days followed by the addition of pegIFN/RBV for a total of 12 weeks of combination treatment. Followed by 36 weeks of pegIFN/RBV alone.	Drug: ABT-333 ABT-333 active Drug: pegIFN pegylated interferon-alpha (syringe) Other Name: Pegasys Drug: ribavirin ribavirin (tablet) Other: Placebo Placebo
Experimental: 7. ABT-333 Groups 7-8 ABT-333 or matching placebo monotherapy for 3 days followed by the addition of pegIFN/RBV for a total of 12 weeks of combination treatment. Followed by 36 weeks of pegIFN/RBV alone.	Drug: ABT-333 ABT-333 active Drug: pegIFN pegylated interferon-alpha (syringe) Other Name: Pegasys Drug: ribavirin ribavirin (tablet) Other: Placebo Placebo
Experimental: 6. ABT-072 Groups 4-6 ABT-072 or matching placebo monotherapy for 3 days followed by the addition of pegIFN/RBV for a total of 12 weeks of combination treatment. Followed by 36 weeks of pegIFN/RBV alone.	Drug: ABT-072 ABT-072 active Drug: pegIFN pegylated interferon-alpha (syringe) Other Name: Pegasys Drug: ribavirin ribavirin (tablet) Other: Placebo Placebo
Experimental: 5. ABT-072 Groups 4-6 ABT-072 or matching placebo monotherapy for 3 days followed by the addition of pegIFN/RBV for a total of 12 weeks of combination treatment. Followed by 36 weeks of pegIFN/RBV alone.	Drug: ABT-072 ABT-072 active Drug: pegIFN pegylated interferon-alpha (syringe) Other Name: Pegasys Drug: ribavirin ribavirin (tablet) Other: Placebo Placebo
Experimental: 4. ABT-072 Groups 4-6 ABT-072 or matching placebo monotherapy for 3 days followed by the addition of pegIFN/RBV for a total of 12 weeks of combination treatment. Followed by 36 weeks of pegIFN/RBV alone	Drug: ABT-072 ABT-072 active Drug: pegIFN pegylated interferon-alpha (syringe) Other Name: Pegasys Drug: ribavirin ribavirin (tablet) Other: Placebo Placebo
Experimental: 1. ABT-450/r Groups 1-3 ABT-450/r or matching placebo monotherapy for 3 days followed by the addition of pegIFN/RBV for a total of 12 weeks of combination treatment. Followed by 36 weeks of pegIFN/RBV alone. Subjects randomized to an ABT-450/r treatment group who achieve RVR and have HCV RNA < 25 IU/mL at all subsequent visits will be eligible to stop SOC on or after Study Week 24.	Drug: ABT-450 ABT-450 active Drug: ritonavir ritonavir active Other Name: ABT-538, Norvir Drug: pegIFN pegylated interferon-alpha (syringe) Other Name: Pegasys Drug: ribavirin ribavirin (tablet) Other: Placebo Placebo
Experimental: 2. ABT-450/r Groups 1-3 ABT-450/r or matching placebo monotherapy for 3 days followed by the addition of pegIFN/RBV for a total of 12 weeks of combination treatment. Followed by 36 weeks of pegIFN/RBV alone. Subjects randomized to an ABT-450/r treatment group who achieve RVR and have HCV RNA < 25 IU/mL at all subsequent visits will be eligible to stop SOC on or after Study Week 24.	Drug: ABT-450 ABT-450 active Drug: ritonavir ritonavir active Other Name: ABT-538, Norvir Drug: pegIFN pegylated interferon-alpha (syringe) Other Name: Pegasys Drug: ribavirin ribavirin (tablet) Other: Placebo Placebo
Experimental: 3. ABT-450/r Groups 1-3 ABT-450/r or matching placebo monotherapy for 3 days followed by the addition of pegIFN/RBV for a total of 12 weeks of combination treatment. Followed by 36 weeks of pegIFN/RBV alone. Subjects randomized to an ABT-450/r treatment group who achieve RVR and have HCV RNA < 25 IU/mL at all subsequent visits will be eligible to stop SOC on or after Study Week 24.	Drug: ABT-450 ABT-450 active Drug: ritonavir ritonavir active Other Name: ABT-538, Norvir Drug: pegIFN pegylated interferon-alpha (syringe) Other Name: Pegasys Drug: ribavirin ribavirin (tablet) Other: Placebo Placebo

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Chronic hepatitis C, genotype 1 infection (HCV RNA level greater than or equal to 100,000 IU/mL) at screening.
Liver biopsy within 3 years with histology consistent with 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 post-menopausal for more than 2 years or surgically sterile.
Negative screen for drugs and alcohol.
Negative HBsAg and anti-HIV Ab.
No use of CYP3A and CYP2C8 enzyme inducers or inhibitors within 1 month of dosing.
Be in a condition of general good health, as perceived by the investigator, other than HCV infection.

Exclusion Criteria:

Significant sensitivity to any drug.
Use of herbal supplements within 2 weeks prior to study drug dosing. History of major depression within 2 years.
Prior treatment with any investigational or commercially available anti-HCV agents.
Abnormal laboratory tests.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01074008

Show 26 Study Locations

Sponsors and Collaborators

AbbVie (prior sponsor, Abbott)

Investigators

Study Director:

Daniel Cohen

AbbVie

More Information

No publications provided

Responsible Party:	AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:	NCT01074008 History of Changes
Other Study ID Numbers:	M11-602
Study First Received:	February 22, 2010
Last Updated:	February 6, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

Antiviral Agents
Ribavirin
Ritonavir
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on May 16, 2013

A Randomized Study to Evaluate the Safety, Tolerability and Antiviral Activity of ABT-450, ABT-333 and ABT-072 (Champion2)