Efficacy of Albumin Interferon Alfa-2b With Ribavirin Compared to Peg-IFN Alfa-2a With Ribavirin in IFN Naive Patients Geno2/3

Chronic Hepatitis C Clinical Trial

Official title:

Phase3 Study to Evaluate the Efficacy and Safety of AlbuminInterferon in Combination With Ribavirin Compared With Peginterferon in Combination With Ribavirin in Interferon Alfa Naive Subjects With CHC Genotype 2/3.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00411385
• Other study ID #: HGS1008-C1067
• Secondary ID: ACHIEVE-2/3
• Status: Completed
• Phase: Phase 3
• First received: December 13, 2006
• Last updated: August 1, 2013
• Start date: February 2007
• Est. completion date: October 2008

Study information

• Verified date: August 2013
• Source: Human Genome Sciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics CommitteeBelgium: Federal Agency for Medicines and Health Products, FAMHPBelgium: Institutional Review BoardBrazil: National Health Surveillance AgencyBrazil: National Committee of Ethics in ResearchCanada: Ethics Review CommitteeCanada: Health CanadaFrance: 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 HealthKorea: Food and Drug AdministrationMalaysia: Ministry of HealthMexico: Ethics CommitteeMexico: Ministry of HealthPoland: Ministry of HealthSingapore: Domain Specific Review BoardsSingapore: Health Sciences AuthoritySpain: Spanish Agency of MedicinesSweden: Medical Products AgencySweden: Regional Ethical Review BoardSweden: Swedish National Council on Medical EthicsTaiwan: Department of HealthTaiwan: Institutional Review BoardThailand: Ethical CommitteeThailand: Food and Drug AdministrationUnited 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 2/3 who are IFNa treatment naive.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 933
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• 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 2/3.

• 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 and 1200 micrograms Albumin Interferon Alpha 2a given subcutaneously once every two weeks for 24 weeks
• peginterferon alfa-2a
180 micrograms Pegasys given subcutaneaously once a week for 24 weeks
• Ribavirin
800mg/day for 24 weeks

Locations

Country	Name	City	State
Argentina	Fundación Cidea	Capital Federal	Buenos Aires
Argentina	Hospital Italiano	Capital Federal	Buenos Aires
Argentina	Unidad de Hepatología	Capital Federal	Buenos Aires
Argentina	Hospital Universitario Austral	Pilar	Buenos Aires
Argentina	Htal Pcial del Centenario	Rosario	Santa Fe
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	Gallipoli Research Foundation and Greenslopes Private Hospital	Greenslopes	Queensland
Australia	Austin Hospital	Heidelburg	Victoria
Australia	Royal Bribane & Women's Hospital	Herston	Queensland
Australia	St George Hospital Clinical School of Medicine	Kogarah	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Belgium	CHU Brugmann ULB - site Victor Horta	Brussels
Belgium	UCL	Brussels
Belgium	University Hospital Antwerp	Edegem
Belgium	Ghent University Hospital	Gent
Belgium	CHU Sart Tilman	Liège
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	Ribeirão Preto	SP
Brazil	Hospital Universitário Professor Edgard Santos - Universidade Federal da Bahia	Salvador	BA
Brazil	Hospital das Clínicas da Faculdade de Medicina da USP	São Paulo	SP
Brazil	Hospital Heliópolis	São Paulo	SP
Brazil	Universidade Federal de São Paulo - UNIFESP	São Paulo	SP
Canada	Heritage Medical Research Clinic	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
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
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	P. D. Hinduja National Hospital and Medical Research Centre	Mumbai
India	G.B.Pant Hospital	New Delhi
India	Maulana Azad Medical College and Associated Lok Nayak 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
Korea, Republic of	Bundang CHA Hospital	Bundang
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Pusan National University Hospital	Pusan
Korea, Republic of	Seoul National University Hospital(Bundang)	Seonnam City
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Medical Center(Anam)	Seoul
Korea, Republic of	Korea University Medical Center(Guro)	Seoul
Korea, Republic of	Kyunghee University - Medical center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital(SVR)	Seoul
Korea, Republic of	Yongdong Severance Hospital	Seoul
Korea, Republic of	Aju University Hospital	Suwon
Malaysia	Hospital Alor Setar	Alor Setar
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	HUKM	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Selayang	Selangor
Mexico	Instituto Nac. de Cs Médicas y Nutrición "Salvador Zubirán"	Mexico	DF
Mexico	Clínica Lomas Altas	Mexico City
Mexico	Hosp. Universitario. Monterrey	Monterrey N.L.	CP
Poland	Wojewódzki Szpital Specjalistyczny	Bialystok
Poland	Niepubliczny Zaklad Opieki Zdrowotnej	Czeladz
Poland	Wojewódzki Szpital Zespolony	Kielce
Poland	Szpital Uniwersytecki w Krakowie	Krakow
Poland	Uniwersytet Medyczny	Lodz
Poland	Wojewódzki Szpital Zakazny	Warszawa
Poland	Przychodnia przy Lowieckie	Wroclaw
Puerto Rico	Fundacion de Investigacion de Diego	Santurce
Singapore	CGH	Singapore
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
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	Complejo Hospitalario Nuestra Señora de Valme	Sevilla
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
Sweden	Universitetssjukhuset MAS	Malmö
Sweden	Karolinska Universitetssjukhuset	Stockholm
Taiwan	CCH	Changhua
Taiwan	TCGH-HL	Hualien	R.o.c.
Taiwan	KCGMH	Kaohsiung	R.o.c.
Taiwan	KMUH	Kaohsiung	R.o.c.
Taiwan	CMUH	Taichung
Taiwan	VGH-TC	Taichung	R.o.c.
Taiwan	CMMC	Tainan
Taiwan	NCKUH	Tainan
Taiwan	NTUH	Taipei	R.o.c.
Taiwan	TCGH-TP	Taipei
Taiwan	TSGH	Taipei	R.o.c.
Taiwan	CGMH-LK	Taoyuan	R.o.c.
Thailand	Chulalongkorn Hospital	Bangkok
Thailand	Ramathibodi Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University	Chiang Mai
United Kingdom	Barts and the London NHS Trust	London
United States	University of New Mexico	Albuquerque	New Mexico
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	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Bronx VA Medical Center	Bronx	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Chicago Hospital	Chicago	Illinois
United States	Baylor University Medical Center	Dallas	Texas
United States	University of Colorado	Denver	Colorado
United States	Metropolitan Research	Fairfax	Virginia
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Florida-Gainesville	Gainesville	Florida
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	Regional Gastroenterology Associates of Lancaster, Ltd.	Lancaster	Pennsylvania
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Miami	Miami	Florida
United States	Faculty Practice Associates	New York	New York
United States	New York Hospital - Cornell	New York	New York
United States	NY Presbyterian Medical Center - Columbia Univ. Med Center	New York	New York
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Minnesota Gastroenterology, P.A.	Plymouth	Minnesota
United States	Alamo Medrical Research	San Antonio	Texas
United States	California Pacific Medical Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Human Genome Sciences Inc.	Novartis

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  France,  Germany,  India,  Israel,  Korea, Republic of,  Malaysia,  Mexico,  Poland,  Puerto Rico,  Singapore,  Spain,  Sweden,  Taiwan,  Thailand,  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 48	No
Secondary	Rapid virologic response		Week 4	No
Secondary	Early virologic response		Week 12	No
Secondary	Undetectable HCV RNA		Week 24	No
Secondary	Normalization of ALT (a liver enzyme)		Week 48	Yes
Secondary	Quality of life evaluation		Week 48	No
Secondary	Safety assessments (physical exams, Ae reporting, lab testing/analysis, HADS and Immunogenicity results)		Througout the entire treatment period	Yes