ABT-450 With Ritonavir and ABT-267 and/or ABT-333 With and Without Ribavirin in Genotype 1 Hepatitis C Virus Infected Patients

NCT01464827 | Completed Phase 2 Results DMC

• 2 other identifiers: M11-6522010-022455-31
• Study Type: interventional
• Target: 580
• Locations: 9 countries
• Sites: 97

Brief Summary

This is a study of combination direct-acting antiviral agents (DAA) with or without ribavirin (RBV) in patients with chronic Hepatitis C Virus (HCV).

Conditions

Chronic Hepatitis C; Hepatitis C (HCV); Hepatitis C Genotype 1

Keywords

Hepatitis C Genotype 1; Hepatitis C; Interferon-Free; HCV; Chronic Hepatitis C

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (AEs)

  An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs) and to ribavirin, and rated the severity of each event as either: Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening. A serious adverse event was any event that resulted in death, was life-threatening, resulted in or prolonged hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention.

  From the time of study drug administration until 30 days following discontinuation of study drug administration (up to 28 weeks).

• Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin

  The percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (SVR24), defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than the lower limit of quantitation (LLOQ), without any confirmed quantifiable (≥ LLOQ) post-treatment value before that time point. HCV RNA levels were measured from plasma by a central laboratory. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoint was the comparison between treatment-naïve participants following 8 weeks of treatment with 3 DAAs and ribavirin and those with 12 weeks of treatment with 3 DAAs and ribavirin (Group A versus Group G).

  Post Treatment Week 24

Secondary Outcomes (4)

• Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment of Different Durations With 3 Direct-acting Antiviral Agents (DAAs) and Ribavirin

  Post-Treatment Week 24

• Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 2 DAAs and Ribavirin Versus 3 DAAs and Ribavirin

  Post-Treatment Week 24

• Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 3 DAAs With Versus Without Ribavirin

  Post-Treatment Week 24

• Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders

  Post-Treatment Week 24

Study Arms (14)

Group A

EXPERIMENTAL

Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 8 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group B

EXPERIMENTAL

Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: Ribavirin; Drug: Ritonavir

Group C

EXPERIMENTAL

Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.

Drug: ABT-450; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group D

EXPERIMENTAL

Treatment-naïve participants received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks.

Drug: ABT-450; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group E

EXPERIMENTAL

Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ABT-333 400 mg twice daily for 12 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ritonavir

Group F

EXPERIMENTAL

Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group G

EXPERIMENTAL

Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group H

EXPERIMENTAL

Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group I

EXPERIMENTAL

Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group J

EXPERIMENTAL

Participants who were null-responders to previous HCV treatment received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

Drug: ABT-450; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group K

EXPERIMENTAL

Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group L

EXPERIMENTAL

Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group M

EXPERIMENTAL

Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Group N

EXPERIMENTAL

Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks.

Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

Interventions

ABT-450 DRUG

ABT-450 tablets

Group A; Group B; Group C; Group D; Group E; Group F; Group G; Group H; Group I; Group J; Group K; Group L; Group M; Group N

ABT-333 DRUG

ABT-333 tablets

Also known as: Dasabuvir

Group A; Group B; Group E; Group F; Group G; Group H; Group I; Group K; Group L; Group M; Group N

ABT-267 DRUG

ABT-267 tablets

Also known as: Ombitasvir

Group A; Group C; Group D; Group E; Group F; Group G; Group H; Group I; Group J; Group K; Group L; Group M; Group N

Ribavirin DRUG

Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).

Group A; Group B; Group C; Group D; Group F; Group G; Group H; Group I; Group J; Group K; Group L; Group M; Group N

Ritonavir DRUG

Ritonavir capsules

Also known as: Norvir

Group A; Group B; Group C; Group D; Group E; Group F; Group G; Group H; Group I; Group J; Group K; Group L; Group M; Group N

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females 18-70 years old, inclusive
• Females must be post-menopausal for more than 2 years or surgically sterile or practicing specific forms of birth control
• Chronic hepatitis C virus (HCV), genotype 1 infection
• Treatment-naive OR null-responders to previous treatment with pegylated interferon (pegIFN) and ribavirin (at least 12 weeks of treatment and failure to achieve a 2 log10 HCV RNA decrease at Week 12)
• No evidence of liver cirrhosis

You may not qualify if:

• Significant liver disease with any cause other than HCV as the primary cause
• Positive hepatitis B surface antigen and anti-human immunodeficiency virus antibody
• Positive screen for drugs and alcohol
• Significant sensitivity to any drug
• Use of contraindicated or prohibited medications within 1 month of dosing
• Abnormal laboratory tests

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (97)

Site Reference ID/Investigator# 57583

Birmingham, Alabama, 35209, United States

Location

Site Reference ID/Investigator# 55530

Birmingham, Alabama, 35215, United States

Location

Site Reference ID/Investigator# 55385

Dothan, Alabama, 36305, United States

Location

Site Reference ID/Investigator# 55500

Phoenix, Arizona, 85054, United States

Location

Site Reference ID/Investigator# 55382

Tucson, Arizona, 85724, United States

Location

Site Reference ID/Investigator# 61042

Bakersfield, California, 93301, United States

Location

Site Reference ID/Investigator# 43651

Coronado, California, 92118, United States

Location

Site Reference ID/Investigator# 43652

Costa Mesa, California, 92626, United States

Location

Site Reference ID/Investigator# 59130

Los Angeles, California, 90048, United States

Location

Site Reference ID/Investigator# 43565

San Diego, California, 92123, United States

Location

Site Reference ID/Investigator# 43910

Aurora, Colorado, 80045, United States

Location

Site Reference ID/Investigator# 43572

Bradenton, Florida, 34209, United States

Location

Site Reference ID/Investigator# 43584

Ft. Pierce, Florida, 34982, United States

Location

Site Reference ID/Investigator# 43917

Gainesville, Florida, 32610, United States

Location

Site Reference ID/Investigator# 55384

Jacksonville, Florida, 32256, United States

Location

Site Reference ID/Investigator# 44610

Wellington, Florida, 33414, United States

Location

Site Reference ID/Investigator# 55531

Wellington, Florida, 33414, United States

Location

Site Reference ID/Investigator# 55536

Zephyrhills, Florida, 33542, United States

Location

Site Reference ID/Investigator# 55540

Macon, Georgia, 31201, United States

Location

Site Reference ID/Investigator# 55527

Marietta, Georgia, 30060, United States

Location

Site Reference ID/Investigator# 44621

Chicago, Illinois, 60637, United States

Location

Site Reference ID/Investigator# 43576

Indianapolis, Indiana, 46202-5121, United States

Location

Site Reference ID/Investigator# 55383

Bowling Green, Kentucky, 42101, United States

Location

Site Reference ID/Investigator# 59124

Shreveport, Louisiana, 71105, United States

Location

Site Reference ID/Investigator# 43568

Annapolis, Maryland, 21401, United States

Location

Site Reference ID/Investigator# 55901

Baltimore, Maryland, 21201, United States

Location

Site Reference ID/Investigator# 43588

Lutherville, Maryland, 21093, United States

Location

Site Reference ID/Investigator# 55534

Boston, Massachusetts, 02215, United States

Location

Site Reference ID/Investigator# 43656

Springfield, Massachusetts, 01105, United States

Location

Site Reference ID/Investigator# 43655

Ann Arbor, Michigan, 48109-0848, United States

Location

Site Reference ID/Investigator# 43913

Detroit, Michigan, 48202, United States

Location

Site Reference ID/Investigator# 43587

Saint Paul, Minnesota, 55114, United States

Location

Site Reference ID/Investigator# 43661

Jackson, Mississippi, 39202, United States

Location

Site Reference ID/Investigator# 43569

Kansas City, Missouri, 64131, United States

Location

Site Reference ID/Investigator# 44608

St Louis, Missouri, 63104, United States

Location

Site Reference ID/Investigator# 55526

Egg Harbor, New Jersey, 08234, United States

Location

Site Reference ID/Investigator# 43566

Manhasset, New York, 11030, United States

Location

Site Reference ID/Investigator# 59133

Monticello, New York, 12701, United States

Location

Site Reference ID/Investigator# 43586

New York, New York, 10016, United States

Location

Site Reference ID/Investigator# 43573

New York, New York, 10021, United States

Location

Site Reference ID/Investigator# 55532

Poughkeepsie, New York, 12601, United States

Location

Site Reference ID/Investigator# 55386

Rochester, New York, 14625, United States

Location

Site Reference ID/Investigator# 55538

Charlotte, North Carolina, 28207, United States

Location

Site Reference ID/Investigator# 55522

Fayetteville, North Carolina, 28304, United States

Location

Site Reference ID/Investigator# 55542

Statesville, North Carolina, 28677, United States

Location

Site Reference ID/Investigator# 55533

Cincinnati, Ohio, 45242, United States

Location

Site Reference ID/Investigator# 43665

Cincinnati, Ohio, 45267-0595, United States

Location

Site Reference ID/Investigator# 43585

Medford, Oregon, 97504, United States

Location

Site Reference ID/Investigator# 55539

Portland, Oregon, 97225, United States

Location

Site Reference ID/Investigator# 56622

Philadelphia, Pennsylvania, 19106, United States

Location

Site Reference ID/Investigator# 43592

Germantown, Tennessee, 38138, United States

Location

Site Reference ID/Investigator# 55723

Germantown, Tennessee, 38138, United States

Location

Site Reference ID/Investigator# 43659

Nashville, Tennessee, 37203, United States

Location

Site Reference ID/Investigator# 59132

Houston, Texas, 77005, United States

Location

Site Reference ID/Investigator# 43577

San Antonio, Texas, 78215, United States

Location

Site Reference ID/Investigator# 43662

Annandale, Virginia, 22003, United States

Location

Site Reference ID/Investigator# 43666

Newport News, Virginia, 23602, United States

Location

Site Reference ID/Investigator# 43574

Seattle, Washington, 98101, United States

Location

Site Reference ID/Investigator# 43578

Madison, Wisconsin, 53792-5124, United States

Location

Site Reference ID/Investigator# 55387

Milwaukee, Wisconsin, 53215, United States

Location

Site Reference ID/Investigator# 44850

Adelaide, 5000, Australia

Location

Site Reference ID/Investigator# 44849

Herston, QLD 4029, Australia

Location

Site Reference ID/Investigator# 44852

Kogarah, 2217, Australia

Location

Site Reference ID/Investigator# 44084

Calgary, T2N 4Z6, Canada

Location

Site Reference ID/Investigator# 43905

Vancouver, V5Z 1H2, Canada

Location

Site Reference ID/Investigator# 44755

Clichy, 92110, France

Location

Site Reference ID/Investigator# 44758

Créteil, 94010, France

Location

Site Reference ID/Investigator# 58884

Lyon, 69004, France

Location

Site Reference ID/Investigator# 58887

Marseille, 13285, France

Location

Site Reference ID/Investigator# 58886

Montpellier, 34295, France

Location

Site Reference ID/Investigator# 44754

Paris, 75679, France

Location

Site Reference ID/Investigator# 58889

Pessac, 33600, France

Location

Site Reference ID/Investigator# 44760

Vandœuvre-lès-Nancy, 54511, France

Location

Site Reference ID/Investigator# 59304

Berlin, 10969, Germany

Location

Site Reference ID/Investigator# 59303

Berlin, 13353, Germany

Location

Site Reference ID/Investigator# 46103

Frankfurt, 60590, Germany

Location

Site Reference ID/Investigator# 46106

Hamburg, 20099, Germany

Location

Site Reference ID/Investigator# 46102

Hanover, 30625, Germany

Location

Site Reference ID/Investigator# 58922

Kiel, 24146, Germany

Location

Site Reference ID/Investigator# 46105

Würzburg, 97080, Germany

Location

Site Reference ID/Investigator# 44847

Auckland, 1142, New Zealand

Location

Site Reference ID/Investigator# 43672

San Juan, 00927, Puerto Rico

Location

Site Reference ID/Investigator# 43675

San Juan, 00936-5067, Puerto Rico

Location

Site Reference ID/Investigator# 46485

Barcelona, 08003, Spain

Location

Site Reference ID/Investigator# 45363

Barcelona, 08028, Spain

Location

Site Reference ID/Investigator# 45668

Barcelona, 08035, Spain

Location

Site Reference ID/Investigator# 46484

Madrid, 28034, Spain

Location

Site Reference ID/Investigator# 45667

Madrid, 28046, Spain

Location

Site Reference ID/Investigator# 45671

Majadahonda (Madrid), 28220, Spain

Location

Site Reference ID/Investigator# 46583

Seville, 41014, Spain

Location

Site Reference ID/Investigator# 45405

Valencia, 46014, Spain

Location

Site Reference ID/Investigator# 57545

Dundee, DD1 9SY, United Kingdom

Location

Site Reference ID/Investigator# 59262

London, E1 1BB, United Kingdom

Location

Site Reference ID/Investigator# 57547

London, NW3 2QG, United Kingdom

Location

Site Reference ID/Investigator# 58811

London, SE5 9RS, United Kingdom

Location

Site Reference ID/Investigator# 57882

Nottingham, NG7 2UH, United Kingdom

Location

Site Reference ID/Investigator# 57543

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• Krishnan P, Tripathi R, Schnell G, Reisch T, Beyer J, Irvin M, Xie W, Larsen L, Cohen D, Podsadecki T, Pilot-Matias T, Collins C. Resistance analysis of baseline and treatment-emergent variants in hepatitis C virus genotype 1 in the AVIATOR study with paritaprevir-ritonavir, ombitasvir, and dasabuvir. Antimicrob Agents Chemother. 2015 Sep;59(9):5445-54. doi: 10.1128/AAC.00998-15. Epub 2015 Jun 22.

  PMID: 26100711 DERIVED

• Kowdley KV, Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, Everson GT, Kwo P, Foster GR, Sulkowski MS, Xie W, Pilot-Matias T, Liossis G, Larsen L, Khatri A, Podsadecki T, Bernstein B. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014 Jan 16;370(3):222-32. doi: 10.1056/NEJMoa1306227.

  PMID: 24428468 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

paritaprevir; dasabuvir; ombitasvir; Ribavirin; Ritonavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Daniel Cohen, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2011
• First Posted: November 4, 2011
• Study Start: October 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: September 1, 2013
• Last Updated: April 22, 2015
• Results First Posted: January 6, 2015

Record last verified: 2015-04

Locations

FR (8); ES (8); DE (7); PR (2); CA (2); US (60); AU (3); GB (6); NZ (1)