Clinical trial NCT00402428: Efficacy of Albumin Interferon Alfa-2b With Ribavirin Compared With Peg-IFN Alfa-2a With Ribavirin in IFN Naive Patients
Official title: Phase 3 Study to Evaluate the Efficacy and Safety of Albumin Interferon Alfa-2b in Combination With Ribavirin Compared With Peginterferon Alfa-2a in Combination With Ribavirin in Interferon Alfa Naive Subjects With CHC Genotype 1. ACHIEVE-1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis C
Keywords: Chronic Hepatitis C
Hepatitis C
CHC
HepC
Genotype 1
Hepatitis
HCV
Lead sponsor: Human Genome Sciences Inc.
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2006-11-22
Enrollment: 1331
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 3, randomized, multi-center study to evaluate the efficacy and safety of albumin interferon alfa 2b (alb-IFN)in combination with ribavirin compared with peginterferon alfa-2a (PEGASYS or PEG-IFNa2a) in combination with ribavirin in subjects with chronic hepatitis C, genotype 1 who are IFNa treatment naive.


Eligibility criteria: Key Inclusion Criteria:

* Diagnosis of chronic hepatitis C.
* Liver biopsy performed within 2 years of Day 0 or during screening.
* Infected with hepatitis C virus genotype 1.
* Interferon alfa treatment naïve (ie, have never been treated with an interferon product).
* Subjects are eligible to enter the study if they (or their partners) are not pregnant or nursing, are sterile, or of non childbearing potential, or are willing to practice abstinence or use appropriate birth control methods during the study and for 7 months after the last dose of ribavirin.
* Have compensated liver disease.

Key Exclusion Criteria:

* Decompensated liver disease including those subjects with a past history or presence of ascites, bleeding varices or hepatic encephalopathy.
* History of moderate, severe or uncontrolled psychiatric disease, especially depression, including a history of hospitalization or prior suicidal attempt.
* Positive for human immunodeficiency virus (HIV-1) or hepatitis B surface antigen (HBsAG).
* Clinical diagnosis of other causes of chronic liver disease including but not limited to hepatitis B, autoimmune hepatitis, primary biliary cirrhosis, alcoholic liver disease, hemochromatosis, Wilson's Disease, or alpha 1-antitrypsin deficiency.
* A history of immunologically mediated disease (eg, rheumatoid arthritis, inflammatory bowel disease, moderate/severe psoriasis, sarcoidosis, systemic lupus erythematosus).
* Active seizure disorder within the last 2 years.
* Organ transplant other than cornea and hair transplant.
* Clinically significant hemoglobinopathy (eg, thalassemia, sickle cell anemia).
* Cancer within the last 5 years(with the exception of adequately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix).
* Drug or alcohol addiction within the last 6 months. Subjects in a supervised methadone treatment program may be enrolled in the study.
* Received any experimental agent within 28 days prior to Day 0.

Primary outcomes:
measure: Sustained virologic response (SVR)
timeFrame: Week 72
Secondary outcomes:
measure: Rapid virologic response
timeFrame: Week 4
measure: Early virologic response
timeFrame: Week 12
measure: Undetectable HCV RNA
timeFrame: Week 24 and Week 48
measure: Normalization of ALT (a liver enzyme)
timeFrame: Week 48
measure: Quality of life evaluation
timeFrame: throughout the entire study
measure: Safety assessments (physical exams, AE reporting, lab testing/analysis, HADS and Immunogenicity testing)
timeFrame: Throughout the entire study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Fresno
country: United States
facility: UCSF Fresno
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: USC Keck School of Medicine
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA / West LA VAMC
state: California
city: Pasadena
country: United States
facility: Huntington Medical Research Institutes
state: California
city: San Diego
country: United States
facility: University California-San Diego
state: California
city: San Diego
country: United States
facility: San Diego Digestive Diseases Consultants, Inc
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Englewood
country: United States
facility: University of Colorado Health Sciences Ctr
state: Colorado
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida - Gainesville
state: Florida
city: Jacksonville
country: United States
facility: Shands Jacksonville Medical Center
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Transplant Center
state: Florida
city: Miami
country: United States
facility: Va Health Care System
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: N. Miami Beach
country: United States
facility: Venture Research Institute
state: Florida
city: Sarasota
country: United States
facility: University Hepatitis Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Atlanta
country: United States
facility: GI of Atlanta
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Gastroenterology Associates
state: Georgia
city: Honolulu
country: United States
facility: Alan D Tice, MD, LLC
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiania University School of Medicine
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Center for Viral Hepatits
state: Maryland
city: Laurel
country: United States
facility: Maryland Digestive Disease Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Tupelo
country: United States
facility: Digestive Health Specialist
state: Mississippi
city: St Louis
country: United States
facility: St. Louis University
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: New York Hospital - Cornell
state: New York
city: New York
country: United States
facility: Faculty Practice Associates
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of University of PA
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Germantown
country: United States
facility: Memphis Gastroenterology Group
state: Tennessee
city: Nashville
country: United States
facility: Nashville Gastroenterology
state: Tennessee
city: Nashville
country: United States
facility: Nashville Gastrointestinal Specialists
state: Tennessee
city: Dallas
country: United States
facility: Liver Institute at Methodist Dallas
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwesten Medical Center
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Granbury
country: United States
facility: GI & Liver Assoicates
state: Texas
city: Houston
country: United States
facility: Liver Specialist of Texas
state: Texas
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Annandale
country: United States
facility: INOVA Fairfax Hospital
state: Virginia
city: Fairfax
country: United States
facility: Metropolitan Research
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Ctr
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital Clinical School of Medicine University of New South Wales
state: New South Wales
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Greenslopes
country: Australia
facility: Greenslopes Private Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy, Victoria
country: Australia
facility: St Vincent's Hospital
state: Victoria
city: Footscray
country: Australia
facility: Western Hospital
state: Victoria
city: Heidelburg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Graz
country: Austria
facility: Medizinische Universitätsklinik Graz
city: Innsbruck
country: Austria
facility: Univ.-Klinik fuer Innere Medizin
city: Wien
country: Austria
facility: Medical University of Vienna
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba Health Sciences Centre
state: Manitoba
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: London
country: Canada
facility: University of Western Ontario Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Brno
country: Czech Republic
facility: Klinika infekcních chorob
city: Hradec Kralove
country: Czech Republic
facility: Klinika Infekcních nemocí
city: Melnik
country: Czech Republic
facility: Nemocnice s poliklinikou Melník
city: Opava
country: Czech Republic
facility: Slezská nemocnice
city: Praha 2
country: Czech Republic
facility: Vseobecna fakultní nemocnice
city: Praha 4
country: Czech Republic
facility: Nuselská poliklinika
city: Usti nad Labem
country: Czech Republic
facility: Ambulance pro interni a infekcni nemoci
city: Clichy
country: France
facility: Hopital Beaujon
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Lyon Cedex 02
country: France
facility: CHU de Lyon, Hôpital de l'Hôtel Dieu
city: Marseille Cedex 08
country: France
facility: Hopital Saint-Joseph
city: Orleans
country: France
facility: Hopital de La Source
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hopital Pitie-Salpetriere
city: Pessac cedex
country: France
facility: Hopital Haut-Leveque
city: Toulouse Cedex
country: France
facility: CHU Purpan Clinique Dieulafoy
city: Vandoeuvre
country: France
facility: Hôpital de Brabois
city: Berlin
country: Germany
facility: UH Charite Berlin / Virchow Klinikum
city: Duesseldorf
country: Germany
facility: Universitätsklinik Düsseldorf
city: Düsseldorf
country: Germany
facility: Center for HIV and Hepatogastroenterology
city: Essen
country: Germany
facility: UH Essen
city: Frankfurt / Main
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet
city: Freiburg
country: Germany
facility: Albert-Ludwigs-Universitaet Freiburg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH)
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universitaet Mainz
city: Marl
country: Germany
facility: Paracelsus Klinik der Stadt Marl
city: Ludhiana
country: India
facility: Dayanand Medical College and Hospital
city: Mumbai
country: India
facility: Jaslok Hospital and Research Centre and Breach Candy Hospital,
city: New Delhi
country: India
facility: G.B.Pant Hospital
city: Haifa
country: Israel
facility: Bnei-Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization
city: Nazareth
country: Israel
facility: Holy Family Hospital
city: Petach Tikva
country: Israel
facility: Rabin Medical Center Beilinson Campus
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bologna
country: Italy
facility: Policlinico S.Orsola Malpighi
city: Milano
country: Italy
facility: IRCCS Ospedale Maggiore, Fondazione Policlinico Mangiagalli e Regina Elena, Università di Milano
city: Napoli
country: Italy
facility: Seconda Università di Napoli c/o Secondo Policlinico
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
city: Pavia
country: Italy
facility: I.R.C.C.S. Policlinico S. Matteo Università degli Studi di Pavia
city: San Giovanni Rotondo (FG)
country: Italy
facility: Casa Sollievo della Sofferenza IRCCS
city: Torino
country: Italy
facility: Azienda Ospedaliera S. Giovanni Battista Molinette
city: Białystok
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im.K. Dłuskiego
city: Chorzow
country: Poland
facility: Szpital Specjalistyczny
city: Kielce
country: Poland
facility: Wojewódzki Szpital Zespolony
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Warszawa
country: Poland
facility: Akademia Medyczna
city: Warszawa
country: Poland
facility: Wojewódzki Szpital Zaka?ny
city: Wrocław
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego
city: Łódź
country: Poland
facility: Uniwersytet Medyczny
city: Santurce
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
city: Bucharest
country: Romania
facility: Spitalul Clinic Colentina
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni
city: Bucharest
country: Romania
facility: Spitalul Clinic Dr.Victor Babes
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic de Adulti Cluj-Napoca
city: Lasi
country: Romania
facility: Institutul de Gastroenterologie si Hepatologie
city: Badalona - Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hopital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Carlos III
city: Valencia
country: Spain
facility: Consorcio Hospital General Universitario de Valencia
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Medical Centre
city: London
country: United Kingdom
facility: Royal London Hospital
city: London
country: United Kingdom
facility: Imperial College London St Mary's Hospital Campus
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust Queens Medical Centre Campus
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bain VG, Yoshida EM, Kaita KD, Swain MG, Heathcote EJ, Garcia A, Moore PA, Yu R, McHutchison JG, Subramanian GM. Dynamics of interferon-specific gene expression in peripheral blood of interferon alfa-naive patients with genotype 1 chronic hepatitis C infection treated with albumin-interferon alfa. Hepatol Res. 2006 Aug;35(4):256-62. doi: 10.1016/j.hepres.2006.04.005. Epub 2006 May 30.
citation: Bain VG, Kaita KD, Yoshida EM, Swain MG, Heathcote EJ, Neumann AU, Fiscella M, Yu R, Osborn BL, Cronin PW, Freimuth WW, McHutchison JG, Subramanian GM. A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. J Hepatol. 2006 Apr;44(4):671-8. doi: 10.1016/j.jhep.2005.12.011. Epub 2006 Jan 30.
citation: S. Zeuzem, , Y. Benhamou, , D. Shouval, , V. Bain, S. Pianko, , R. Flisiak, , M. Grigorescu, , V. Rehak, , E. Yoshida, K. Kaita, , C. Hezode, A.U. Neumann, M. Subramanian, J. McHutchison. Interim (Week 12) Phase 2B Virological Efficacy and Safety Results of albumin interferon alfa-2b Combined with Ribavirin in Genotype 1 Chronic Hepatitis C Infection. EASL, 2006
citation: Vinod Rustgi, et al. A Dose-Escalation Study of albumin alfa-Ribavirin in Non-responders to Prior Interferon Based Therapy for Chronic Hepatitis C Infection Phase 2 Dose A Phase 2 Dose-Escalation Study of albumin interferon alfa interferon alfa-2b Combined with 2b Combined with Ribavirin in Non Non-responders to Prior Interferon. EASL, 2006
citation: Balan V, Nelson DR, Sulkowski MS, Everson GT, Lambiase LR, Wiesner RH, Dickson RC, Post AB, Redfield RR, Davis GL, Neumann AU, Osborn BL, Freimuth WW, Subramanian GM. A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy. Antivir Ther. 2006;11(1):35-45.
citation: Zeuzem S, Sulkowski MS, Lawitz EJ, Rustgi VK, Rodriguez-Torres M, Bacon BR, Grigorescu M, Tice AD, Lurie Y, Cianciara J, Muir AJ, Cronin PW, Pulkstenis E, Subramanian GM, McHutchison JG; ACHIEVE-1 Study Team. Albinterferon Alfa-2b was not inferior to pegylated interferon-alpha in a randomized trial of patients with chronic hepatitis C virus genotype 1. Gastroenterology. 2010 Oct;139(4):1257-66. doi: 10.1053/j.gastro.2010.06.066. Epub 2010 Jun 27.