Efficacy of Albumin Interferon Alfa-2b With Ribavirin Compared With Peg-IFN Alfa-2a With Ribavirin in IFN Naive Patients

Chronic Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00402428
• Other study ID #: HGS1008-C1060
• Secondary ID: ACHIEVE-1
• Status: Completed
• Phase: Phase 3
• First received: November 20, 2006
• Last updated: August 1, 2013
• Start date: December 2006
• Est. completion date: February 2009

Study information

• Verified date: August 2013
• Source: Human Genome Sciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics CommitteeAustria: Agency for Health and Food SafetyAustria: EthikkommissionCanada: Ethics Review CommitteeCanada: Health CanadaCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: National Consultative Ethics Committee for Health and Life SciencesGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesIndia: Institutional Review BoardIsrael: Ministry of HealthItaly: Ethics CommitteeItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthPoland: Ministry of HealthRomania: National Medicines AgencySpain: Spanish Agency of MedicinesSwitzerland: EthikkommissionSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics CommitteeUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1331
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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 C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• albumin interferon alfa-2b
900 mcg or 1200mcg every two week for 48 weeks
• peginterferon alfa-2a
180 mcg once a week for 48 weeks
• Ribavirin
1000 mg/day(for subjects <75kg) or 1200 mg/day (for subjects =,> 75kg)

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	St Vincent's Hospital	Fitzroy, Victoria	Victoria
Australia	Western Hospital	Footscray	Victoria
Australia	Fremantle Hospital	Fremantle	Western Australia
Australia	Greenslopes Private Hospital	Greenslopes	Queensland
Australia	Austin Hospital	Heidelburg	Victoria
Australia	St George Hospital Clinical School of Medicine University of New South Wales	Kogarah	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal Perth Hospital	Perth
Australia	Westmead Hospital	Westmead	New South Wales
Austria	Medizinische Universitätsklinik Graz	Graz
Austria	Univ.-Klinik fuer Innere Medizin	Innsbruck
Austria	Medical University of Vienna	Wien
Canada	Heritage Medical Research Clinic	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Dalhousie University	Halifax	Nova Scotia
Canada	University of Western Ontario Hospital	London	Ontario
Canada	McGill University	Montreal	Quebec
Canada	Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	University of Manitoba Health Sciences Centre	Winnipeg	Manitoba
Czech Republic	Klinika infekcních chorob	Brno
Czech Republic	Klinika Infekcních nemocí	Hradec Kralove
Czech Republic	Nemocnice s poliklinikou Melník	Melnik
Czech Republic	Slezská nemocnice	Opava
Czech Republic	Vseobecna fakultní nemocnice	Praha 2
Czech Republic	Nuselská poliklinika	Praha 4
Czech Republic	Ambulance pro interni a infekcni nemoci	Usti nad Labem
France	Hopital Beaujon	Clichy
France	Hopital Henri Mondor	Creteil
France	CHU de Lyon, Hôpital de l'Hôtel Dieu	Lyon Cedex 02
France	Hopital Saint-Joseph	Marseille Cedex 08
France	Hopital de La Source	Orleans
France	Hopital Pitie-Salpetriere	Paris
France	Hôpital Saint-Antoine	Paris
France	Hopital Haut-Leveque	Pessac cedex
France	CHU Purpan Clinique Dieulafoy	Toulouse Cedex
France	Hôpital de Brabois	Vandoeuvre
Germany	UH Charite Berlin / Virchow Klinikum	Berlin
Germany	Universitätsklinik Düsseldorf	Duesseldorf
Germany	Center for HIV and Hepatogastroenterology	Düsseldorf
Germany	UH Essen	Essen
Germany	Klinikum der Johann Wolfgang Goethe-Universitaet	Frankfurt / Main
Germany	Albert-Ludwigs-Universitaet Freiburg	Freiburg
Germany	Medizinische Hochschule Hannover (MHH)	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Johannes Gutenberg-Universitaet Mainz	Mainz
Germany	Paracelsus Klinik der Stadt Marl	Marl
India	Dayanand Medical College and Hospital	Ludhiana
India	Jaslok Hospital and Research Centre and Breach Candy Hospital,	Mumbai
India	G.B.Pant Hospital	New Delhi
Israel	Bnei-Zion Medical Center	Haifa
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Organization	Jerusalem
Israel	Holy Family Hospital	Nazareth
Israel	Rabin Medical Center Beilinson Campus	Petach Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Policlinico S.Orsola Malpighi	Bologna
Italy	IRCCS Ospedale Maggiore, Fondazione Policlinico Mangiagalli e Regina Elena, Università di Milano	Milano
Italy	Seconda Università di Napoli c/o Secondo Policlinico	Napoli
Italy	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo
Italy	I.R.C.C.S. Policlinico S. Matteo Università degli Studi di Pavia	Pavia
Italy	Casa Sollievo della Sofferenza IRCCS	San Giovanni Rotondo (FG)
Italy	Azienda Ospedaliera S. Giovanni Battista Molinette	Torino
Poland	Wojewódzki Szpital Specjalistyczny im.K. Dluskiego	Bialystok
Poland	Szpital Specjalistyczny	Chorzow
Poland	Wojewódzki Szpital Zespolony	Kielce
Poland	Szpital Uniwersytecki w Krakowie	Kraków
Poland	Uniwersytet Medyczny	Lódz
Poland	Akademia Medyczna	Warszawa
Poland	Wojewódzki Szpital Zaka?ny	Warszawa
Poland	Wojewódzki Szpital Specjalistyczny im. J. Gromkowskiego	Wroclaw
Puerto Rico	Fundacion de Investigacion de Diego	Santurce
Romania	Institutul Clinic Fundeni	Bucharest
Romania	Spitalul Clinic Colentina	Bucharest
Romania	Spitalul Clinic Dr.Victor Babes	Bucharest
Romania	Spitalul Clinic de Adulti Cluj-Napoca	Cluj-Napoca
Romania	Institutul de Gastroenterologie si Hepatologie	Lasi
Spain	Hospital Universitari Germans Trias i Pujol	Badalona - Barcelona
Spain	Hopital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital Carlos III	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
United Kingdom	Queen Elizabeth Medical Centre	Birmingham
United Kingdom	Imperial College London St Mary's Hospital Campus	London
United Kingdom	Royal London Hospital	London
United Kingdom	Nottingham University Hospitals NHS Trust Queens Medical Centre Campus	Nottingham
United Kingdom	Derriford Hospital	Plymouth
United States	University of New Mexico	Albuquerque	New Mexico
United States	INOVA Fairfax Hospital	Annandale	Virginia
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	GI of Atlanta	Atlanta	Georgia
United States	Johns Hopkins Center for Viral Hepatits	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Liver Institute at Methodist Dallas	Dallas	Texas
United States	UT Southwesten Medical Center	Dallas	Texas
United States	University of Colorado	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke Medical Center	Durham	North Carolina
United States	University of Colorado Health Sciences Ctr	Englewood	Colorado
United States	Metropolitan Research	Fairfax	Virginia
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	UCSF Fresno	Fresno	California
United States	University of Florida - Gainesville	Gainesville	Florida
United States	Memphis Gastroenterology Group	Germantown	Tennessee
United States	GI & Liver Assoicates	Granbury	Texas
United States	Alan D Tice, MD, LLC	Honolulu	Hawaii
United States	Liver Specialist of Texas	Houston	Texas
United States	Indiania University School of Medicine	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Mayo Clinic Transplant Center	Jacksonville	Florida
United States	Shands Jacksonville Medical Center	Jacksonville	Florida
United States	Scripps Clinic	La Jolla	California
United States	Maryland Digestive Disease Center	Laurel	Maryland
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	UCLA / West LA VAMC	Los Angeles	California
United States	USC Keck School of Medicine	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Northwest Georgia Gastroenterology Associates	Marietta	Georgia
United States	University of Miami	Miami	Florida
United States	Va Health Care System	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Venture Research Institute	N. Miami Beach	Florida
United States	Nashville Gastroenterology	Nashville	Tennessee
United States	Nashville Gastrointestinal Specialists	Nashville	Tennessee
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Faculty Practice Associates	New York	New York
United States	New York Hospital - Cornell	New York	New York
United States	Huntington Medical Research Institutes	Pasadena	California
United States	Hospital of University of PA	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Virginia Commonwealth University Medical Ctr	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Alamo Medical Research	San Antonio	Texas
United States	San Diego Digestive Diseases Consultants, Inc	San Diego	California
United States	University California-San Diego	San Diego	California
United States	VA San Diego Healthcare	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	University of California at San Francisco	San Francisco	California
United States	University Hepatitis Center	Sarasota	Florida
United States	University of Washington	Seattle	Washington
United States	St. Louis University	St Louis	Missouri
United States	Digestive Health Specialist	Tupelo	Mississippi
United States	Walter Reed Army Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Human Genome Sciences Inc.	Novartis

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Czech Republic,  France,  Germany,  India,  Israel,  Italy,  Poland,  Puerto Rico,  Romania,  Spain,  United Kingdom, 

References & Publications (5)

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. Epub 2006 Jan 30. — View 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-naïve patients with genotype 1 chronic hepatitis C infection treated with albumin-interferon alfa. Hepatol Res. 2006 Aug;35(4):256-62. Epub 2006 May 30. — View 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. — View 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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response (SVR)		Week 72	No
Secondary	Rapid virologic response		Week 4	No
Secondary	Early virologic response		Week 12	No
Secondary	Undetectable HCV RNA		Week 24 and Week 48	No
Secondary	Normalization of ALT (a liver enzyme)		Week 48	Yes
Secondary	Quality of life evaluation		throughout the entire study	No
Secondary	Safety assessments (physical exams, AE reporting, lab testing/analysis, HADS and Immunogenicity testing)		Throughout the entire study	Yes