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

Chronic Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01464827
• Other study ID #: M11-652
• Secondary ID: 2010-022455-31
• Status: Completed
• Phase: Phase 2
• First received: September 28, 2011
• Last updated: April 2, 2015
• Start date: October 2011
• Est. completion date: September 2013

Study information

• Verified date: April 2015
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaFrance: Afssaps - Agence francaise de securite sanitaire des produits de sante (Saint-Denis)Spain: Agencia Española de Medicamentos y Productos SanitariosGermany: Federal Institute for Drugs and Medical DevicesNew Zealand: MedsafeCzech Republic: State Institute for Drug ControlUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyChile: Ministry of HealthMexico: Ministry of HealthBrazil: National Health Surveillance AgencyArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 580
• Est. completion date: September 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C (HCV)
• Hepatitis C Genotype 1
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• ABT-450
ABT-450 tablets
• ABT-333
ABT-333 tablets
• ABT-267
ABT-267 tablets
• Ribavirin
Ribavirin tablets administered at a weight-based dose, between 1,000 to 1,200 mg daily (divided).
• Ritonavir
Ritonavir capsules

Locations

Country	Name	City	State
Australia	Site Reference ID/Investigator# 44850	Adelaide
Australia	Site Reference ID/Investigator# 44849	Herston
Australia	Site Reference ID/Investigator# 44852	Kogarah
Canada	Site Reference ID/Investigator# 44084	Calgary
Canada	Site Reference ID/Investigator# 43905	Vancouver
France	Site Reference ID/Investigator# 44755	Clichy
France	Site Reference ID/Investigator# 44758	Creteil
France	Site Reference ID/Investigator# 58884	Lyon
France	Site Reference ID/Investigator# 58887	Marseilles
France	Site Reference ID/Investigator# 58886	Montpellier - Cedex 5
France	Site Reference ID/Investigator# 44754	Paris
France	Site Reference ID/Investigator# 58889	Pessac
France	Site Reference ID/Investigator# 44760	Vandoeuvre Les Nancy
Germany	Site Reference ID/Investigator# 59303	Berlin
Germany	Site Reference ID/Investigator# 59304	Berlin
Germany	Site Reference ID/Investigator# 46103	Frankfurt
Germany	Site Reference ID/Investigator# 46106	Hamburg
Germany	Site Reference ID/Investigator# 46102	Hannover
Germany	Site Reference ID/Investigator# 58922	Kiel
Germany	Site Reference ID/Investigator# 46105	Wuerzburg
New Zealand	Site Reference ID/Investigator# 44847	Auckland
Puerto Rico	Site Reference ID/Investigator# 43672	San Juan
Puerto Rico	Site Reference ID/Investigator# 43675	San Juan
Spain	Site Reference ID/Investigator# 45363	Barcelona
Spain	Site Reference ID/Investigator# 45668	Barcelona
Spain	Site Reference ID/Investigator# 46485	Barcelona
Spain	Site Reference ID/Investigator# 45667	Madrid
Spain	Site Reference ID/Investigator# 46484	Madrid
Spain	Site Reference ID/Investigator# 45671	Majadahonda (Madrid)
Spain	Site Reference ID/Investigator# 46583	Seville
Spain	Site Reference ID/Investigator# 45405	Valencia
United Kingdom	Site Reference ID/Investigator# 57545	Dundee
United Kingdom	Site Reference ID/Investigator# 57547	London
United Kingdom	Site Reference ID/Investigator# 58811	London
United Kingdom	Site Reference ID/Investigator# 59262	London
United Kingdom	Site Reference ID/Investigator# 57882	Nottingham
United Kingdom	Site Reference ID/Investigator# 57543	Southampton
United States	Site Reference ID/Investigator# 43655	Ann Arbor	Michigan
United States	Site Reference ID/Investigator# 43662	Annandale	Virginia
United States	Site Reference ID/Investigator# 43568	Annapolis	Maryland
United States	Site Reference ID/Investigator# 43910	Aurora	Colorado
United States	Site Reference ID/Investigator# 61042	Bakersfield	California
United States	Site Reference ID/Investigator# 55901	Baltimore	Maryland
United States	Site Reference ID/Investigator# 55530	Birmingham	Alabama
United States	Site Reference ID/Investigator# 57583	Birmingham	Alabama
United States	Site Reference ID/Investigator# 55534	Boston	Massachusetts
United States	Site Reference ID/Investigator# 55383	Bowling Green	Kentucky
United States	Site Reference ID/Investigator# 43572	Bradenton	Florida
United States	Site Reference ID/Investigator# 55538	Charlotte	North Carolina
United States	Site Reference ID/Investigator# 44621	Chicago	Illinois
United States	Site Reference ID/Investigator# 43665	Cincinnati	Ohio
United States	Site Reference ID/Investigator# 55533	Cincinnati	Ohio
United States	Site Reference ID/Investigator# 43651	Coronado	California
United States	Site Reference ID/Investigator# 43652	Costa Mesa	California
United States	Site Reference ID/Investigator# 43913	Detroit	Michigan
United States	Site Reference ID/Investigator# 55385	Dothan	Alabama
United States	Site Reference ID/Investigator# 55526	Egg Harbor Township	New Jersey
United States	Site Reference ID/Investigator# 55522	Fayetteville	North Carolina
United States	Site Reference ID/Investigator# 43584	Fort Pierce	Florida
United States	Site Reference ID/Investigator# 43917	Gainesville	Florida
United States	Site Reference ID/Investigator# 43592	Germantown	Tennessee
United States	Site Reference ID/Investigator# 55723	Germantown	Tennessee
United States	Site Reference ID/Investigator# 59132	Houston	Texas
United States	Site Reference ID/Investigator# 43576	Indianapolis	Indiana
United States	Site Reference ID/Investigator# 43661	Jackson	Mississippi
United States	Site Reference ID/Investigator# 55384	Jacksonville	Florida
United States	Site Reference ID/Investigator# 43569	Kansas City	Missouri
United States	Site Reference ID/Investigator# 59130	Los Angeles	California
United States	Site Reference ID/Investigator# 43588	Lutherville	Maryland
United States	Site Reference ID/Investigator# 55540	Macon	Georgia
United States	Site Reference ID/Investigator# 43578	Madison	Wisconsin
United States	Site Reference ID/Investigator# 43566	Manhasset	New York
United States	Site Reference ID/Investigator# 55527	Marietta	Georgia
United States	Site Reference ID/Investigator# 43585	Medford	Oregon
United States	Site Reference ID/Investigator# 55387	Milwaukee	Wisconsin
United States	Site Reference ID/Investigator# 59133	Monticello	New York
United States	Site Reference ID/Investigator# 43659	Nashville	Tennessee
United States	Site Reference ID/Investigator# 43573	New York	New York
United States	Site Reference ID/Investigator# 43586	New York	New York
United States	Site Reference ID/Investigator# 43666	Newport News	Virginia
United States	Site Reference ID/Investigator# 56622	Philadelphia	Pennsylvania
United States	Site Reference ID/Investigator# 55500	Phoenix	Arizona
United States	Site Reference ID/Investigator# 55539	Portland	Oregon
United States	Site Reference ID/Investigator# 55532	Poughkeepsie	New York
United States	Site Reference ID/Investigator# 55386	Rochester	New York
United States	Site Reference ID/Investigator# 43577	San Antonio	Texas
United States	Site Reference ID/Investigator# 43565	San Diego	California
United States	Site Reference ID/Investigator# 43574	Seattle	Washington
United States	Site Reference ID/Investigator# 59124	Shreveport	Louisiana
United States	Site Reference ID/Investigator# 43656	Springfield	Massachusetts
United States	Site Reference ID/Investigator# 44608	St. Louis	Missouri
United States	Site Reference ID/Investigator# 43587	St. Paul	Minnesota
United States	Site Reference ID/Investigator# 55542	Statesville	North Carolina
United States	Site Reference ID/Investigator# 55382	Tucson	Arizona
United States	Site Reference ID/Investigator# 44610	Wellington	Florida
United States	Site Reference ID/Investigator# 55531	Wellington	Florida
United States	Site Reference ID/Investigator# 55536	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  New Zealand,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Yes
Primary	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	No
Secondary	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).	Post-Treatment Week 24	No
Secondary	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).	Post-Treatment Week 24	No
Secondary	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).	Post-Treatment Week 24	No
Secondary	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).	Post-Treatment Week 24	No

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