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

October 15, 2010
September 9, 2013
December 2010
September 2012   (final data collection date for primary outcome measure)
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
  • 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: at week 4 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 8 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 12 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 16 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 20 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 24 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • any presence of anti-CEP-33457 antibodies (Ab)
    • concomitant medication usage
  • 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: at week 28 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 32 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 36 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 40 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 44 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • physical examination findings
    • concomitant medication usage
  • 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: at week 48 ] [ Designated as safety issue: Yes ]

    Safety will be assessed by evaluating the following:

    • occurrence of adverse events
    • clinical laboratory tests
    • vital signs measurements
    • 12-lead electrocardiography (ECG) - also measured if early termination
    • physical examination findings
    • any presence of anti-CEP-33457 antibodies (Ab) - also measured if early termination
    • concomitant medication usage
Complete list of historical versions of study NCT01240694 on ClinicalTrials.gov Archive Site
  • 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
  • Proportion of patients achieving a clinical response using the SLE responder index (SRI) at each visit during the treatment period [ Time Frame: at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ] [ 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 weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ] [ 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 weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ] [ 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 weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ] [ 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, and 36 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, and 36; 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: during the overall 48 week study period ] [ Designated as safety issue: No ]

    Biological markers-

    • anti-double-stranded deoxyribonucleic acid antibody (anti dsDNA Ab)
    • complement components (C3 and C4)
    • 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 weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 ] [ 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 week 24 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 48 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 48 week study period ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Long-Term Study of the Safety and Tolerability of Repeated Administration of CEP-33457 in Patients With Systemic Lupus Erythematosus
An Open-Label Long-Term Study of the Safety and Tolerability of Repeated Administration of CEP-33457 in Patients With Systemic Lupus Erythematosus

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).

Not Provided
Interventional
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Systemic Lupus Erythematosus
Drug: CEP-33457
200 mcg of CEP-33457
Experimental: CEP-33457
200 mcg of CEP-33457
Intervention: Drug: CEP-33457
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
136
September 2012
September 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   Czech Republic,   France,   Germany,   Hungary,   Poland,   Portugal,   Spain,   Ukraine,   United Kingdom
 
NCT01240694
C33457/3075
Not Provided
Teva Pharmaceutical Industries ( Cephalon )
Cephalon
Not Provided
Study Director: Sponsor's Medical Expert Cephalon
Teva Pharmaceutical Industries
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP