Chronic Hepatitis CPhase 2NCT01464827

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

A Phase 2 study testing ABT-450, ABT-333 and ABT-267 in people with Chronic Hepatitis C and Hepatitis C (HCV), run by AbbVie (prior sponsor, Abbott) at 97 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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). Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Chronic Hepatitis C, Hepatitis C (HCV), Hepatitis C Genotype 1
What is being tested?: ABT-450, ABT-333 and ABT-267
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 580 participants
Where: 97 sitesin 9 countries
Study dates: Oct 2011to Sep 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

97 sites in 9 countries.

Country

City, postcode or hospital

97 sites in 9 countries

United States60 sites

Site Reference ID/Investigator# 43655
Ann Arbor, Michigan, 48109-0848
Site Reference ID/Investigator# 43662
Annandale, Virginia, 22003
Site Reference ID/Investigator# 43568
Annapolis, Maryland, 21401
Site Reference ID/Investigator# 43910
Aurora, Colorado, 80045
Site Reference ID/Investigator# 61042
Bakersfield, California, 93301
Site Reference ID/Investigator# 55901
Baltimore, Maryland, 21201
Site Reference ID/Investigator# 57583
Birmingham, Alabama, 35209
Site Reference ID/Investigator# 55530
Birmingham, Alabama, 35215
Site Reference ID/Investigator# 55534
Boston, Massachusetts, 02215
Site Reference ID/Investigator# 55383
Bowling Green, Kentucky, 42101
Site Reference ID/Investigator# 43572
Bradenton, Florida, 34209
Site Reference ID/Investigator# 55538
Charlotte, North Carolina, 28207
Site Reference ID/Investigator# 44621
Chicago, Illinois, 60637
Site Reference ID/Investigator# 55533
Cincinnati, Ohio, 45242
Site Reference ID/Investigator# 43665
Cincinnati, Ohio, 45267-0595
Site Reference ID/Investigator# 43651
Coronado, California, 92118
Site Reference ID/Investigator# 43652
Costa Mesa, California, 92626
Site Reference ID/Investigator# 43913
Detroit, Michigan, 48202
Site Reference ID/Investigator# 55385
Dothan, Alabama, 36305
Site Reference ID/Investigator# 55526
Egg Harbor, New Jersey, 08234
Site Reference ID/Investigator# 55522
Fayetteville, North Carolina, 28304
Site Reference ID/Investigator# 43584
Ft. Pierce, Florida, 34982
Site Reference ID/Investigator# 43917
Gainesville, Florida, 32610
Site Reference ID/Investigator# 43592
Germantown, Tennessee, 38138
Site Reference ID/Investigator# 55723
Germantown, Tennessee, 38138
Site Reference ID/Investigator# 59132
Houston, Texas, 77005
Site Reference ID/Investigator# 43576
Indianapolis, Indiana, 46202-5121
Site Reference ID/Investigator# 43661
Jackson, Mississippi, 39202
Site Reference ID/Investigator# 55384
Jacksonville, Florida, 32256
Site Reference ID/Investigator# 43569
Kansas City, Missouri, 64131
Site Reference ID/Investigator# 59130
Los Angeles, California, 90048
Site Reference ID/Investigator# 43588
Lutherville, Maryland, 21093
Site Reference ID/Investigator# 55540
Macon, Georgia, 31201
Site Reference ID/Investigator# 43578
Madison, Wisconsin, 53792-5124
Site Reference ID/Investigator# 43566
Manhasset, New York, 11030
Site Reference ID/Investigator# 55527
Marietta, Georgia, 30060
Site Reference ID/Investigator# 43585
Medford, Oregon, 97504
Site Reference ID/Investigator# 55387
Milwaukee, Wisconsin, 53215
Site Reference ID/Investigator# 59133
Monticello, New York, 12701
Site Reference ID/Investigator# 43659
Nashville, Tennessee, 37203
Site Reference ID/Investigator# 43586
New York, New York, 10016
Site Reference ID/Investigator# 43573
New York, New York, 10021
Site Reference ID/Investigator# 43666
Newport News, Virginia, 23602
Site Reference ID/Investigator# 56622
Philadelphia, Pennsylvania, 19106
Site Reference ID/Investigator# 55500
Phoenix, Arizona, 85054
Site Reference ID/Investigator# 55539
Portland, Oregon, 97225
Site Reference ID/Investigator# 55532
Poughkeepsie, New York, 12601
Site Reference ID/Investigator# 55386
Rochester, New York, 14625
Site Reference ID/Investigator# 43587
Saint Paul, Minnesota, 55114
Site Reference ID/Investigator# 43577
San Antonio, Texas, 78215
Site Reference ID/Investigator# 43565
San Diego, California, 92123
Site Reference ID/Investigator# 43574
Seattle, Washington, 98101
Site Reference ID/Investigator# 59124
Shreveport, Louisiana, 71105
Site Reference ID/Investigator# 43656
Springfield, Massachusetts, 01105
Site Reference ID/Investigator# 44608
St Louis, Missouri, 63104
Site Reference ID/Investigator# 55542
Statesville, North Carolina, 28677
Site Reference ID/Investigator# 55382
Tucson, Arizona, 85724
Site Reference ID/Investigator# 44610
Wellington, Florida, 33414
Site Reference ID/Investigator# 55531
Wellington, Florida, 33414
Site Reference ID/Investigator# 55536
Zephyrhills, Florida, 33542

Other trials in United States

France8 sites

Site Reference ID/Investigator# 44755
Clichy, 92110
Site Reference ID/Investigator# 44758
Créteil, 94010
Site Reference ID/Investigator# 58884
Lyon, 69004
Site Reference ID/Investigator# 58887
Marseille, 13285
Site Reference ID/Investigator# 58886
Montpellier, 34295
Site Reference ID/Investigator# 44754
Paris, 75679
Site Reference ID/Investigator# 58889
Pessac, 33600
Site Reference ID/Investigator# 44760
Vandœuvre-lès-Nancy, 54511

Other trials in France

Spain8 sites

Site Reference ID/Investigator# 46485
Barcelona, 08003
Site Reference ID/Investigator# 45363
Barcelona, 08028
Site Reference ID/Investigator# 45668
Barcelona, 08035
Site Reference ID/Investigator# 46484
Madrid, 28034
Site Reference ID/Investigator# 45667
Madrid, 28046
Site Reference ID/Investigator# 45671
Majadahonda (Madrid), 28220
Site Reference ID/Investigator# 46583
Seville, 41014
Site Reference ID/Investigator# 45405
Valencia, 46014

Other trials in Spain

Germany7 sites

Site Reference ID/Investigator# 59304
Berlin, 10969
Site Reference ID/Investigator# 59303
Berlin, 13353
Site Reference ID/Investigator# 46103
Frankfurt, 60590
Site Reference ID/Investigator# 46106
Hamburg, 20099
Site Reference ID/Investigator# 46102
Hanover, 30625
Site Reference ID/Investigator# 58922
Kiel, 24146
Site Reference ID/Investigator# 46105
Würzburg, 97080

Other trials in Germany

United Kingdom6 sites

Site Reference ID/Investigator# 57545
Dundee, DD1 9SY
Site Reference ID/Investigator# 59262
London, E1 1BB
Site Reference ID/Investigator# 57547
London, NW3 2QG
Site Reference ID/Investigator# 58811
London, SE5 9RS
Site Reference ID/Investigator# 57882
Nottingham, NG7 2UH
Site Reference ID/Investigator# 57543
Southampton, SO16 6YD

Other trials in United Kingdom

Australia3 sites

Site Reference ID/Investigator# 44850
Adelaide, 5000
Site Reference ID/Investigator# 44849
Herston, QLD 4029
Site Reference ID/Investigator# 44852
Kogarah, 2217

Other trials in Australia

Canada2 sites

Site Reference ID/Investigator# 44084
Calgary, T2N 4Z6
Site Reference ID/Investigator# 43905
Vancouver, V5Z 1H2

Other trials in Canada

Puerto Rico2 sites

Site Reference ID/Investigator# 43672
San Juan, 00927
Site Reference ID/Investigator# 43675
San Juan, 00936-5067

Other trials in Puerto Rico

New Zealand1 site

Site Reference ID/Investigator# 44847
Auckland, 1142

Other trials in New Zealand

About this study

Official title: A Randomized, Open-Label, Multicenter Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics, of ABT-450 With Ritonavir (ABT-450/r) in Combination With ABT-267 and/or ABT-333 With and Without Ribavirin (RBV) for 8, 12 or 24 Weeks in Treatment-Naïve and Null Responder Subjects With Genotype 1 Chronic Hepatitis C Virus Infection

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

Read the detailed description

A study to evaluate the safety and effectiveness of experimental drugs ABT-450, ABT-267 (also known as ombitasvir), ABT-333 (also known as dasabuvir), ritonavir, and ribavirin in participants with HCV. The study will test the safety and effects of combinations of these drugs in treatments up to 24 weeks.

Conditions: Chronic Hepatitis C, Hepatitis C (HCV), Hepatitis C Genotype 1
Being tested: ABT-450, ABT-333, ABT-267, Ribavirin, Ritonavir
Keywords: Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, HCV, Chronic Hepatitis C
Medical subject headings: Hepatitis C, Chronic, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ABT-450Drug
ABT-450 tablets
ABT-333Drug
Also called Dasabuvir
ABT-333 tablets
ABT-267Drug
Also called Ombitasvir
ABT-267 tablets
RibavirinDrug
Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).
RitonavirDrug
Also called Norvir
Ritonavir capsules

Study groups in NCT01464827
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: ABT-450; Drug: ABT-333; Drug: ABT-267; Drug: Ribavirin; Drug: Ritonavir

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
Measured: 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
This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 3 DAAs (ABT-450/ritonavir, ABT-267, and ABT-333) and ribavirin in both treatment naïve and null-responder participants for 8 weeks (Group A) versus 12 weeks (Groups F + G + K + L) versus 24 weeks (Groups H + I + M + N).
Measured: 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
This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 2 DAAs (ABT-450/ritonavir plus ABT-333 [Group B] or ABT-450/ritonavir plus ABT-267 [Groups C + D + J]) and ribavirin versus 3 DAAs (ABT-450/ritonavir plus ABT-333 and ABT-267) and ribavirin (Groups F + G + K + L).
Measured: 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
This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 3 DAAs with or without ribavirin (Group E versus Groups F + G + K + L).
Measured: Post-Treatment Week 24
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders
This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA < LLOQ at post-treatment Week 24) following treatment with 3 DAAs and ribavirin in participants who were treatment-naïve versus those who were null-responders to previous HCV therapy (Groups F + G + H + I versus Groups K + L + M + N).
Measured: Post-Treatment Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2011Sep 2013

First posted4 Nov 2011 (estimated)
Study startOct 2011
Primary completionMar 2013
Study completionSep 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 580 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01464827
Sponsor's protocol ID: M11-652
Other IDs: 2010-022455-31
Status last verified: Apr 2015
First submitted: 28 Sep 2011
Last updated: 22 Apr 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 26100711
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.
PubMed 24428468

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Chronic Hepatitis C trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open-Label, Multicenter Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics, of ABT-450 With Ritonavir (ABT-450/r) in Combination With ABT-267 and/or ABT-333 With and Without Ribavirin (RBV) for 8, 12 or 24 Weeks in Treatment-Naïve and Null Responder Subjects With Genotype 1 Chronic Hepatitis C Virus Infection
ClinicalTrials.gov ID: NCT01464827
Acronym / sponsor ID: M11-652
Conditions: Chronic Hepatitis C, Hepatitis C (HCV), Hepatitis C Genotype 1
Keywords: Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, HCV, Chronic Hepatitis C
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 580 participants (actual)
Lead sponsor: AbbVie (prior sponsor, Abbott)Industry (pharma, biotech, devices)
Study start: Oct 2011
Primary completion: Mar 2013 (actual)
Study completion: Sep 2013 (actual)
First posted: 4 Nov 2011 (estimated)
Results: Posted 6 Jan 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 14

Arm	Type	Receives
Group A	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirTreatment-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.
Group B	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: Ribavirin, Drug: RitonavirTreatment-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.
Group C	Experimental	Drug: ABT-450, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirTreatment-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.
Group D	Experimental	Drug: ABT-450, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirTreatment-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.
Group E	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: RitonavirTreatment-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.
Group F	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirTreatment-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.
Group G	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirTreatment-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.
Group H	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirTreatment-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.
Group I	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirTreatment-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.
Group J	Experimental	Drug: ABT-450, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirParticipants 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.
Group K	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirParticipants 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.
Group L	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirParticipants 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.
Group M	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirParticipants 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.
Group N	Experimental	Drug: ABT-450, Drug: ABT-333, Drug: ABT-267, Drug: Ribavirin, Drug: RitonavirParticipants 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ABT-450ABT-450 tablets	Drug	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-333Also: DasabuvirABT-333 tablets	Drug	Group A, Group B, Group E, Group F, Group G, Group H, Group I, Group K, Group L, Group M, Group N
ABT-267Also: OmbitasvirABT-267 tablets	Drug	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
RibavirinRibavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).	Drug	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
RitonavirAlso: NorvirRitonavir capsules	Drug	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

Primary outcome

Number of Participants With Adverse Events (AEs)
Time frame: From the time of study drug administration until 30 days following discontinuation of study drug administration (up to 28 weeks).
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.
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin
Time frame: Post Treatment Week 24
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).

4 secondary outcomes

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
Time frame: 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
Time frame: 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
Time frame: Post-Treatment Week 24
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders
Time frame: Post-Treatment Week 24

Results and safety

Results posted to the registry on 6 Jan 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A	80	77
Group B	43	36
Group C	39	39
Group D	40	36
Group E	80	72
Group F	39	38
Group G	41	37
Group H	40	37
Group I	40	37
Group J	47	44
Group K	23	21
Group L	23	21
Group M	23	21
Group N	22	19

Primary outcome: Number of Participants With Adverse Events (AEs)

Time frame: From the time of study drug administration until 30 days following discontinuation of study drug administration (up to 28 weeks).. Number. Unit: participants

Measure	Group A n = 80	Group B n = 41	Group C + D n = 79	Group E n = 79	Group F + G n = 79	Group H + I n = 80	Group J n = 45	Group K + L n = 45	Group M + N n = 45
Any adverse event	67	36	71	68	71	77	42	39	37
Any adverse event at least possibly DAA-related	58	29	53	51	57	68	35	30	28
Any severe adverse event	3	0	3	5	3	3	1	1	1
Any serious adverse event	0	0	2	2	1	1	0	0	2
Any AE leading to discontinuation of study drug	1	0	0	0	3	3	1	0	1
Any AE leading to interruption of study drug	0	1	2	1	0	1	0	0	0
Any AE leading to ribavirin dose modification	2	2	4	0	9	10	3	1	3
Any fatal adverse events	0	0	0	0	0	0	0	0	0

Population analysed: Safety population. Treatment groups differing only in ABT-450 dose (100 mg, 150 mg or 200 mg) were combined for safety analyses.

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

Time frame: Post Treatment Week 24. Number. Unit: percentage of participants

Measure	Group A n = 80	Group B n = 41	Group C n = 39	Group D n = 40	Group E n = 79	Group F n = 39	Group G n = 40	Group H n = 40	Group I n = 40	Group J n = 45	Group K n = 23	Group L n = 22	Group M n = 23	Group N n = 20
Value	87.5	82.9	84.6	92.5	88.6	97.4	95.0	92.5	90.0	88.9	91.3	95.5	91.3	100.0

Group A vs Group G: Odds Ratio (OR): 0.49 (95% CI 0.09 to 2.61), p = 0.406, Regression, Logistic

Population analysed: Intent-to-treat population (all participants who received at least 1 dose of direct-acting antiviral agent); participants with missing data were counted as non-responders.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 28 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A	0 of 80 (0%)	64 of 80 (80%)	Not reported
Group B	0 of 41 (0%)	33 of 41 (80.5%)	Not reported
Group C + D	2 of 79 (2.5%)	66 of 79 (83.5%)	Not reported
Group E	2 of 79 (2.5%)	59 of 79 (74.7%)	Not reported
Group F + G	1 of 79 (1.3%)	66 of 79 (83.5%)	Not reported
Group H + I	1 of 80 (1.3%)	74 of 80 (92.5%)	Not reported
Group J	0 of 45 (0%)	40 of 45 (88.9%)	Not reported
Group K + L	0 of 45 (0%)	36 of 45 (80%)	Not reported
Group M + N	2 of 43 (4.7%)	34 of 43 (79.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26100711Krishnan 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.
Derived from this study: PubMed 24428468Kowdley 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.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Daniel Cohen, MD study director

AbbVie

97 sites in 9 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ABT-450, ABT-333 and ABT-267 in people with Chronic Hepatitis C and Hepatitis C (HCV), run by AbbVie (prior sponsor, Abbott) at 97 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 97 sites in United States, France, Spain, Germany, United Kingdom and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs) (time frame: From the time of study drug administration until 30 days following discontinuation of study drug administration (up to 28 weeks).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01464827, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2015.