Patients With Systemic Lupus Erythematosus (SLE) MedDRA version: 14.0 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Cephalon, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are included in the study if all of the following criteria are met: (a) The patient is a man or woman between 18 and 70 years of age with an established diagnosis of SLE as defined by ACR Classification Revised Criteria. The diagnosis is fulfilled provided that at least 4 criteria are met. (b) The patient has a positive test for ANA at screening (titer must be at least 1:80 [by human epithelial cell tumor line (HEp 2) ANA assay]) and/or a positive test for anti dsDNA Ab at screening (value must be 30 IU/mL or more by ELISA). (c) Written informed consent is obtained. (d) 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. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method. (e) The patient has a clinical SLEDAI 2K score of at least 6 points during screening. A clinical SLEDAI 2K score is the calculated score without inclusion of the points that may be contributed by having a positive titer for anti dsDNA Ab or decreased serum complement levels. (f) The patient does not have an “A” score on the BILAG 2004 scale. (g) If the patient is using oral corticosteroids, the weekly cumulative dose must not exceed 80 mg of prednisone equivalent; the weekly dose must be stable over the 4 weeks preceding the 1st dose of study drug. (h) If the patient is using antimalarials, methotrexate, leflunomide, mycophenolate mofetil, or azathioprine, the start date must be at least 3 months prior to the 1st dose of study drug, and the daily dose must be stable over the 4 weeks preceding the 1st dose of study drug. (i) If the patient is not currently using corticosteroids, antimalarials, methotrexate, mycophenolate mofetil, or azathioprine, the last dose (in case of previous use) must be at least 4 weeks prior to the 1st dose of study drug. For leflunomide, the stop date must be at least 8 weeks before the 1st dose of study drug, unless an adequate cholestyramine washout has been completed. (j) The patient must be willing and able to comply with study restrictions, to remain at the study center for the required duration during each study visit, and to return to the study center for the final assessment as specified in this protocol. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 216 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Patients are excluded from participating in this study if 1 or more of the following criteria are met: (a) The patient has been treated with intramuscular or iv pulse steroids (ie, 250 to 1000 mg iv total daily dose of methylprednisolone) within 4 weeks of the 1st dose of study drug. The use of intra articular steroids may be allowed after consultation with the medical expert. (b) The patient has received tacrolimus, cyclosporine A, or intravenous immunoglobulins (IVIG) within 3 months of the 1st dose of study drug. (c) The patient has received cyclophosphamide within 12 months prior to the 1st dose of study drug. (d) The patient has been treated for SLE with agents such as fusion proteins, therapeutic proteins, or monoclonal antibodies or antibody fragments, within 12 months of the 1st dose of study drug. (e) The patient has received B cell depleting agents such as rituximab and has not yet normalized the B cell count (ie, CD20+ B cell count is less than 200 and the absolute lymphocyte count [ALC] is less than 1500/µL). (f) The patient has New York Heart Association (NYHA) Class III or IV congestive heart failure. (g) The patient has severe active lupus nephritis or cerebritis. (h1) 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). (i) 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 the ULN. (j) The patient has a planned immunization with a live or live attenuated vaccine within 3 months prior to administration of the 1st dose of study drug and for 3 months after administration of the last dose of study drug. (k1) The patient has any clinically significant abnormalities on the 12- lead 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. (l) 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 1st dose of study drug. Less severe infections in the 3 months prior to administration of the 1st dose of study drug are permitted at the discretion of the investigator and medical monitor. (m1) 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. (n) The patient has a history of a medical condition other than SLE that has required treatment with steroids in excess of 80 mg of prednisone equivalent/week within 6 months of the 1st dose of study drug. (o) The patient has a positive test result for HBsAg or HCV Ab. (p) The patient has a known positive history of antibodies to human immunodeficiency virus (HIV) or HIV disease. (q) 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 or has current substance abuse. (r) The patient has a history of severe allergic reactions to or hypersensitivity to any component of the study drug or pla
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy of a 200 mcg dose of CEP 33457 compared with placebo in patients with active systemic lupus erythematosus (SLE) as assessed by the proportion of patients achieving a combined clinical response using the SLE responder index (SRI) at week 24. 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 new British Isles Lupus Assessment Group A (BILAG A) body system score, and no more than 1 new BILAG B body system score from baseline.;Secondary Objective: •efficacy objectives ?SRI response ?reduction of at least 4 points in the SLEDAI 2K total score ?disease activity (BILAG 2004 disease activity index) ?status of disease (PhGA and Patient’s Global Assessment scales) ?health related QoL (SF 36 and the Lupus QoL Questionnaires) ?arthritis (28 joint count examination for pain and tenderness) ?cutaneous manifestations of disease (CLASI) ?biologic markers of disease activity (eg serology B [autoantibodies, complement components, immunoglobulins, interleukins]) and immunophenotyping) ?incidence of disease flares (ie SELENA Flare Index and SLEDAI 2K score>15) ?occurrence of SLE induced organ damage (eg SLICC/ACR Damage Index and AEs) ?change in steroid dose ?QoL •safety objectives ?AEs ?clinical laboratory (serum chemistry, hematology and urinalysis) ?vital signs (blood pressure, pulse, temperature, and body weight) ?12 lead ECG ?physical examination ?concomitant medication;Primary end point(s): The primary efficacy variable for this study is the proportion of patients achieving a combined clinical response using the SRI at week 24. An SRI response is defined as a reduction from baseline in the SLEDAI 2K score of at least 4 points; no worsening in PhGA (wi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy variables and endpoints for this study are as follows: • proportion of patients achieving an SRI response at each visit during the treatment period • proportion of patients achieving a reduction of at least 4 points in the SLEDAI-2K total score at each visit during the treatment period • proportion of patients achieving a clinical SLEDAI-2K response at each visit during the treatment period, where the clinical response is defined as a reduction of at least 4 points in the SLEDAI-2K clinical score • proportion of patients achieving a BILAG-2004 response at each visit during the treatment period (no new A body system score and no more than 1 new BILAG B body system score from baseline) • proportion of patients achieving a BILAG-2004 clinical response at each visit during the treatment period (an improvement in at least 1 category from a B score to a C or D score, with no worsening in any other category) • proportion of patients showing no worsening on a global assessment scale at each visit (physician and patient) during the treatment period • absolute and relative changes in the SF-36 at week 12 and the final assessment (week 24 or early termination);Timepoint(s) of evaluation of this end point: each visit | — |
Countries
Belgium, Czech Republic, France, Germany, Hungary, Poland, Portugal, Spain, Ukraine, United States
Contacts
Public ContactBrian Dove
PPD
Outcome results
None listed