A Long-Term Study of the Safety and Tolerability of Repeated Administration of CEP-33457 in Patients With Systemic Lupus Erythematosus

This study has been terminated.
(Business Decision; there were no safety issues)
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier:
NCT01240694
First received: October 15, 2010
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

The primary objective of this study is to evaluate the long term safety and tolerability of repeated administration of subcutaneous (sc) CEP 33457 for injection every 4 weeks over 72 weeks (18 doses) in patients with systemic lupus erythematosus (SLE) who have participated in a previous Cephalon sponsored clinical study of CEP 33457, and completed at least visit 8 (week 24 of that study).


Condition Intervention Phase
Systemic Lupus Erythematosus
Drug: CEP-33457
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Long-Term Study of the Safety and Tolerability of Repeated Administration of CEP-33457 in Patients With Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • To evaluate the long term safety and tolerability of repeated administration of subcutaneous (sc) CEP-33457 in patients with systemic lupus erythematosus (SLE) [ Time Frame: each 4 week interval up to a total duration of 72 weeks ] [ Designated as safety issue: Yes ]

    Overall Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage


Secondary Outcome Measures:
  • Proportion of patients achieving a clinical response using the SLE responder index (SRI) at each visit during the treatment period [ Time Frame: at each 4 week interval up to Week 72 ] [ Designated as safety issue: No ]
    An SRI response is defined as a reduction from baseline in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) score of at least 4 points, no worsening in Physician's Global Assessment (PhGA) (with worsening defined as an increase in PhGA of more than 0.30 point from baseline), no British Isles Lupus Assessment Group A (BILAG A) organ domain score, and no more than 1 new BILAG B organ domain score from baseline.

  • Assessment of disease activity according to the change in the SLEDAI-2K score at each visit during the treatment period [ Time Frame: at each 4 week interval up to Week 72 ] [ Designated as safety issue: No ]
    SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index 2000. It is a global index and includes 24 weighted clinical and laboratory variables.

  • Measure of disease activity based upon the physician intention to treat according to the change in the BILAG-2004 score at each visit during the treatment period [ Time Frame: at each 4 week interval up to Week 72 ] [ Designated as safety issue: No ]
    BILAG-2004 = British Isles Lupus Assessment Group 2004. BILAG-2004 includes 97 clinical and laboratory items to evaluate SLE disease activity in 9 organ systems.

  • The effect of CEP-33457 on the status of disease (PhGA scale) at each visit during the treatment period [ Time Frame: at each 4 week interval up to Week 72 ] [ Designated as safety issue: No ]
  • The effect of CEP-33457 on the status of disease (Patient's Global Assessment [PtGA] scale) [ Time Frame: at weeks 12, 24, 36, 48 and 60 and the final assessment (or early termination) ] [ Designated as safety issue: No ]
  • The effect of CEP-33457 on health related quality of life, as assessed by completion of the Medical Outcome Survey Short Form 36 (SF 36) [ Time Frame: at weeks 12, 24, 36, 48 and 60 and the final assessment (or early termination) ] [ Designated as safety issue: No ]
  • The effect of CEP-33457 on biologic markers of disease activity during the study [ Time Frame: At weeks 12, 24, 36, 48, 60, and the final assessment (or early termination) ] [ Designated as safety issue: No ]

    Biological markers-

    • anti-U1 ribonucleoprotein antibody (anti U1RNP Ab)
    • anti-Smith antibody (anti Sm Ab)
    • C-reactive protein (CRP)
    • immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin E (IgE)
    • antinuclear antibody (ANA)

  • The effect of CEP-33457 on the incidence of disease flares, eg, Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) Flare Index [ Time Frame: at each 4 week interval up to Week 72 ] [ Designated as safety issue: No ]
  • The effect of CEP-33457 on the occurrence of systemic lupus erythematosus-induced (SLE-induced) organ damage [ Time Frame: at weeks 24, 48, and the final assessment (or early termination) ] [ Designated as safety issue: No ]
    e.g., Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index

  • Remission of disease [ Time Frame: during the overall 72 week study period ] [ Designated as safety issue: No ]
    (i.e., reduction of SLEDAI-2K score to 0)

  • Proportion of patients with changes in steroid dose over time throughout the study [ Time Frame: during the overall 72 week study period ] [ Designated as safety issue: No ]
  • Presence of anti-CEP-33457 antibodies [ Time Frame: at weeks 24, 48, and final assessment (or early termination) ] [ Designated as safety issue: No ]
    This is an assessment of the immunogenicity of CEP-33457


Enrollment: 136
Study Start Date: December 2010
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CEP-33457
200 mcg of CEP-33457
Drug: CEP-33457
200 mcg of CEP-33457

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has an established diagnosis of systemic lupus erythematosus (SLE) as defined by ACR Classification Revised Criteria. The diagnosis is fulfilled provided that at least 4 criteria are met.
  • The patient previously participated in and completed at least visit 8 (week 24) the Cephalon sponsored clinical study with CEP 33457 (study C33457/2047) and, in the investigator's opinion, would benefit from continued participation in a clinical study.
  • Women must be surgically sterile, 2 years postmenopausal, or, if of childbearing potential, using a medically accepted method of contraception, and must agree to continued use of this method for the duration of the study and for 30 days after discontinuation of study drug treatment.

Exclusion Criteria:

  • The patient has New York Heart Association (NYHA) Class III or IV congestive heart failure.
  • The patient has an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2 (via Modification of Diet in Renal Disease [MDRD] equation).
  • The patient has an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value greater than 2 times the upper limit of normal (ULN) or a total bilirubin level greater than 1.5 times ULN.
  • The patient has a planned immunization with a live or live attenuated vaccine within 3 months prior to administration of the first dose of study drug and for 3 months after administration of the last dose of study drug.
  • The patient has any clinically significant abnormalities on ECG that are not related to SLE, as determined by the investigator. Patients with stable ECG changes without evidence of active cardiovascular disease may participate at the discretion of the investigator and medical monitor.
  • The patient has an ongoing active systemic infection requiring treatment or a history of severe infection, such as hepatitis or pneumonia, in the 3 months prior to administration of the first dose of study drug. Less severe infections in the 3 months prior to administration of the first dose of study drug are permitted at the discretion of the investigator and medical monitor.
  • The patient has any concomitant medical condition unrelated to SLE that may interfere with his or her safety or with evaluation of the study drug, as determined by the investigator.
  • The patient has a history of a positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab).
  • The patient has a known positive history of antibodies to human immunodeficiency virus (HIV) or HIV disease.
  • The patient has a history of alcohol or substance dependence or abuse (with the exception of nicotine), according to the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, Fourth Edition, Text Revision (DSM-IV-TR), within 3 months of the screening visit for study C33457/2047, or has current substance abuse.
  • The patient has a history of severe allergic reactions to or hypersensitivity to any component of the study drug.
  • The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
  • The patient has undergone or is undergoing treatment with another investigational drug for the treatment of lupus within 6 months prior to the 1st dose of study drug or has received any other investigational drug for any other condition within 30 days prior to the 1st dose of study drug, except for treatment with CEP-33457 or placebo in study C33457/2047.
  • The patient has a known history of antibodies to CEP-33457.
  • The patient is unlikely to comply with the study protocol or is unsuitable for any other reason, as judged by the investigator or medical monitor.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01240694

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States
United States, Arizona
University of Arizona
Tucson, Arizona, United States
United States, California
Wallace Rheumatic Study Center
Los Angeles, California, United States
University of California, Los Angeles
Los Angeles, California, United States
UCSD VA San Diego Healthcare System
San Diego, California, United States
East Bay Rheumatology
San Leandro, California, United States
Stanford University Medical Center
Stanford, California, United States
United States, Colorado
University of Colorado
Boulder, Colorado, United States
United States, Florida
Arthritis and Rheumatic Disease Specialties
Aventura, Florida, United States
Clincial Research of West Florida, Inc.
Clearwater, Florida, United States
Centre for Rheumatology, Immunology and Arthritis Research
Fort Lauderdale, Florida, United States
Science and Research Institute, Inc
Jupiter, Florida, United States
Tampa Medical Group, Pa
Tampa, Florida, United States
United States, Georgia
Emory University
Atlanta, Georgia, United States
Atlanta Center for Clinical Research
Atlanta, Georgia, United States
Arthritis Research and Treatment Center
Stockbridge, Georgia, United States
United States, Idaho
Coeur D'Alene Arthritis Clinic
Coeur D'Alene, Idaho, United States
United States, Kentucky
Bluegrass Clinical Research, Inc.
Lexington, Kentucky, United States
United States, Maryland
Johns Hopkins University Medical Center
Baltimore, Maryland, United States
United States, Massachusetts
Tufts New England Medical Center
Boston, Massachusetts, United States
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States
United States, New York
Feinstein Institute for Medical Research
Manhasset, New York, United States
United States, North Carolina
University of North Carolina Hospitals
Chapel Hill, North Carolina, United States
Box Arthritis and Rheumatology of the Carolinas PLLC
Charlotte, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Carolina Bone and Joint
Monroe, North Carolina, United States
United States, Oklahoma
SSM Healthcare of Oklahoma, Inc.
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States
Allegheny Singer Research Institute
Pittsburgh, Pennsylvania, United States
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States
United States, Texas
Metroplex Clinical Research Center
Dallas, Texas, United States
Houston Institute For Clinical Research
Houston, Texas, United States
Accurate Clinical Research
Houston, Texas, United States
Southwest Rhuematology, PA
Mesquite, Texas, United States
Arthritis Associates Research, LLC
San Antonio, Texas, United States
Scott - White Clinic/Texas A and M University
Temple, Texas, United States
United States, Virginia
Arthritis Clinic Of Northern Va, P.C.
Arlington, Virginia, United States
United States, Washington
Seattle Rheumatology Associates
Seattle, Washington, United States
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Belgium
UZ Brussel
Brussel, Belgium
CHU de Liège
Liège, Belgium
Cliniques Universitaires UCL de Mont-Godinne
Yvoir, Belgium
Czech Republic
Revmatologie s.r.o.
Brno, Czech Republic
Fakultni nemocnice
Plzen - Bory, Czech Republic
Revmatologicky ustav
Praha 2, Czech Republic
Vseobecna fakultni nemocnice v Praze
Praha 2, Czech Republic
France
Hôpital Claude Huriez
Lille, France
CHU de Nantes - Hotel Dieu
Nantes, France
Hôpital Cochin
Paris, France
Groupe Hospitalier Pitié- Salpétrière
Paris, France
Hôpital de Hautepierre
Strasbourg, France
Germany
University Clinics Aachen
Aachen, Germany
Charité - Universitätsmedizin Berlin
Berlin, Germany
Universitatsklinikum Carl Gustav Carus
Dresden, Germany
Universitätsklinikum Düsseldorf
Düsseldorf, Germany
Klinikum Eilbek
Hamburg, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Germany
LMU Klinikum der Universität
München, Germany
Hungary
Országos Reumatológiai és Fizioterápiás Intézet
Budapest, Hungary
Debreceni Egyetem Orvos- és Egészségtudományi Centrum
Debrecen, Hungary
Zala Megyei Kórház
Zalaegerszeg, Hungary
Poland
Niepubliczny Specjalistyczny Zaklad Opieki Zdrowotnej Unica
Dabrowka, Poland
Wojewodzki Szpital Zespolony
Elblag, Poland
Zespol Opieki Zdrowotnej w Konskich
Konskie, Poland
Samodzielny Publiczny Szpital Kliniczny nr 4
Lublin, Poland
Niepubliczny Zaklad Opieki Zdrowotnej
Lublin, Poland
Linea Corporis- Chirurgia Plastyczna
Warszawa, Poland
Akademicki Szpital Kliniczny we Wroclawiu im. Jana Mikulicza
Wroclaw, Poland
Portugal
Hospital Fernando Fonseca
Amadora, Portugal
Hospitais da Universidade de Coimbra
Coimbra, Portugal
Hospital Geral de Santo Antonio
Porto, Portugal
Hospital de São João
Porto, Portugal
Spain
Hospital Virgen del Rocio
Sevilla, Andalucía, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, Spain
Hospital Vall D´Hebron
Barcelona, Cataluña, Spain
Ukraine
Regional Clinical Hospital for Professional Diseases
Donetsk, Ukraine
Ivano-Frankivsk Regional Clinical Hospital
Ivano-Frankivsk, Ukraine
Olexandrivska Clinical Hospital
Kyiv, Ukraine
Kyiv Regional Clinical Hospital
Kyiv, Ukraine
Institute of Cardiology named after Strazhesko
Kyiv, Ukraine
Lviv Regional Pediatric Hospital
Lviv, Ukraine
United Kingdom
Royal National Hospital for Rheumatic Diseases
Bath, United Kingdom
Chapel Allerton Hospital
Leeds, United Kingdom
St. Thomas Hospital
London, United Kingdom
Freeman Hospital
Newcastle Upon Tyne, United Kingdom
Sponsors and Collaborators
Cephalon
Investigators
Study Director: Sponsor's Medical Expert Cephalon
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Cephalon )
ClinicalTrials.gov Identifier: NCT01240694     History of Changes
Other Study ID Numbers: C33457/3075
Study First Received: October 15, 2010
Last Updated: September 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
Lupus
SLE

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014