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

NCT ID: NCT01074008

Last Updated: 2015-01-08

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

74 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-31

Study Completion Date

2012-01-31

Brief Summary

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This study assessed the safety, tolerability, pharmacokinetics, and antiviral activity of multiple oral doses of ABT-450/ritonavir (r), ABT-333 (also known as dasabuvir), or ABT-072 in hepatitis C virus (HCV), genotype 1-infected, treatment-naïve adults.

Detailed Description

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This was a Phase 2a, randomized, blinded, placebo-controlled, dose-ranging study in chronically, hepatitis C virus (HCV) genotype 1-infected participants designed to explore the safety, tolerability, pharmacokinetics, antiviral activity, as well as the evolution and persistence to resistance of ABT-450/r, ABT-333, or ABT-072. Participants were treated with ABT-450/r, ABT-333, or ABT-072 monotherapy for 3 days, followed by 81 days (12 weeks minus 3 days of monotherapy) of ABT-450/r, ABT-333, or ABT-072 combined with pegylated interferon/ribavirin (pegIFN/RBV), followed by 36 weeks of pegIFN/RBV alone. Participants randomized to an ABT-450/r treatment group who achieved rapid virologic response (RVR) and had HCV ribonucleic acid (RNA) levels \< 25 IU/mL at all subsequent visits were eligible to stop pegIFN/RBV therapy on or after Week 24.

Conditions

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Hepatitis C HCV Chronic Hepatitis C Infection Hepatitis C Genotype 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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ABT-450/r (50/100 mg) once daily (QD) + pegIFN/RBV

Participants received 50 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-450

Intervention Type DRUG

50 mg capsules co-administered with ritonavir

Ritonavir

Intervention Type DRUG

100 mg capsules co-administered with ABT-450

Peginterferon alpha-2a

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-450/r (100/100 mg) once daily (QD) + pegIFN/RBV

Participants received 100 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-450

Intervention Type DRUG

50 mg capsules co-administered with ritonavir

Ritonavir

Intervention Type DRUG

100 mg capsules co-administered with ABT-450

Peginterferon alpha-2a

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-450/r (200/100 mg) once daily (QD) + pegIFN/RBV

Participants received 200 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-450

Intervention Type DRUG

50 mg capsules co-administered with ritonavir

Ritonavir

Intervention Type DRUG

100 mg capsules co-administered with ABT-450

Peginterferon alpha-2a

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-072 (100 mg) once daily (QD) + pegIFN/RBV

Participants received 100 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-072

Intervention Type DRUG

50 mg tablet

Peginterferon alpha-2a

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-072 (300 mg) once daily (QD) + pegIFN/RBV

Participants received 300 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-072

Intervention Type DRUG

50 mg tablet

Peginterferon alpha-2a

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-072 (600 mg) once daily (QD) + pegIFN/RBV

Participants received 600 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-072

Intervention Type DRUG

50 mg tablet

Peginterferon alpha-2a

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-333 (400 mg) twice a day (BID) + pegIFN/RBV

Participants received 400 mg ABT-333 monotherapy twice a day for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-333

Intervention Type DRUG

400 mg tablet

Peginterferon alpha-2a

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

ABT-333 (800 mg) twice daily (BID) + pegIFN/RBV

Participants received 800 mg ABT-333 monotherapy twice a day for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type EXPERIMENTAL

ABT-333

Intervention Type DRUG

400 mg tablet

Peginterferon alpha-2a

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

Placebo + pegIFN/RBV

Participants received matching placebo for ABT-450/r, ABT-072, or ABT-333 monotherapy at each dose level for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.

Group Type PLACEBO_COMPARATOR

Peginterferon alpha-2a

Intervention Type DRUG

Syringe, 180 µg/0.5 mL for subcutaneous injections

Ribavirin

Intervention Type DRUG

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

Placebo

Intervention Type OTHER

Matching placebo for ABT-450/r, ABT-072, or ABT-333 monotherapy at each dose level

Interventions

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ABT-450

50 mg capsules co-administered with ritonavir

Intervention Type DRUG

ABT-072

50 mg tablet

Intervention Type DRUG

ABT-333

400 mg tablet

Intervention Type DRUG

Ritonavir

100 mg capsules co-administered with ABT-450

Intervention Type DRUG

Peginterferon alpha-2a

Syringe, 180 µg/0.5 mL for subcutaneous injections

Intervention Type DRUG

Ribavirin

200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day

Intervention Type DRUG

Placebo

Matching placebo for ABT-450/r, ABT-072, or ABT-333 monotherapy at each dose level

Intervention Type OTHER

Other Intervention Names

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Dasabuvir ABT-538 Norvir

Eligibility Criteria

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Inclusion Criteria

* Chronic hepatitis C virus (HCV), genotype 1 infection (HCV ribonucleic acid 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 hepatitis B surface antigen (HBsAg) and anti-human immunodeficiency virus antibodies (anti-HIV Ab)
* No use of cytochrome P450 3A (CYP3A) and cytochrome P450 2C8 (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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Cohen

Role: STUDY_DIRECTOR

AbbVie

Locations

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Site Reference ID/Investigator# 23392

Phoenix, Arizona, United States

Site Status

Site Reference ID/Investigator# 23370

Anaheim, California, United States

Site Status

Site Reference ID/Investigator# 23387

La Jolla, California, United States

Site Status

Site Reference ID/Investigator# 23388

Los Angeles, California, United States

Site Status

Site Reference ID/Investigator# 23371

Aurora, Colorado, United States

Site Status

Site Reference ID/Investigator# 23369

Orlando, Florida, United States

Site Status

Site Reference ID/Investigator# 26362

Orlando, Florida, United States

Site Status

Site Reference ID/Investigator# 23373

Chicago, Illinois, United States

Site Status

Site Reference ID/Investigator# 24908

Chicago, Illinois, United States

Site Status

Site Reference ID/Investigator# 23381

Indianapolis, Indiana, United States

Site Status

Site Reference ID/Investigator# 23372

Baton Rouge, Louisiana, United States

Site Status

Site Reference ID/Investigator# 24710

New Orleans, Louisiana, United States

Site Status

Site Reference ID/Investigator# 23391

Baltimore, Maryland, United States

Site Status

Site Reference ID/Investigator# 23377

Detroit, Michigan, United States

Site Status

Site Reference ID/Investigator# 24909

Saint Paul, Minnesota, United States

Site Status

Site Reference ID/Investigator# 35842

New York, New York, United States

Site Status

Site Reference ID/Investigator# 23379

New York, New York, United States

Site Status

Site Reference ID/Investigator# 23375

Chapel Hill, North Carolina, United States

Site Status

Site Reference ID/Investigator# 23385

Durham, North Carolina, United States

Site Status

Site Reference ID/Investigator# 23376

Dallas, Texas, United States

Site Status

Site Reference ID/Investigator# 24891

Houston, Texas, United States

Site Status

Site Reference ID/Investigator# 23382

San Antonio, Texas, United States

Site Status

Site Reference ID/Investigator# 24715

Salt Lake City, Utah, United States

Site Status

Site Reference ID/Investigator# 25463

Seattle, Washington, United States

Site Status

Site Reference ID/Investigator# 23383

Madison, Wisconsin, United States

Site Status

Site Reference ID/Investigator# 23363

Ponce, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Pilot-Matias T, Tripathi R, Cohen D, Gaultier I, Dekhtyar T, Lu L, Reisch T, Irvin M, Hopkins T, Pithawalla R, Middleton T, Ng T, McDaniel K, Or YS, Menon R, Kempf D, Molla A, Collins C. In vitro and in vivo antiviral activity and resistance profile of the hepatitis C virus NS3/4A protease inhibitor ABT-450. Antimicrob Agents Chemother. 2015 Feb;59(2):988-97. doi: 10.1128/AAC.04227-14. Epub 2014 Dec 1.

Reference Type DERIVED
PMID: 25451053 (View on PubMed)

Related Links

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Other Identifiers

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M11-602

Identifier Type: -

Identifier Source: org_study_id

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