A Long-Term Study of the Safety and Tolerability of Repeated Administration of CEP-33457 in Participants With Systemic Lupus Erythematosus
- Registration Number
- NCT01240694
- Lead Sponsor
- Cephalon, Inc.
- Brief Summary
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 participants 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 136
- The participant has an established diagnosis of SLE as defined by ACR Classification Revised Criteria. The diagnosis is fulfilled provided that at least 4 criteria are met.
- The participant 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.
- The participant has New York Heart Association (NYHA) Class III or IV congestive heart failure.
- The participant has an estimated glomerular filtration rate (eGFR) of less than 30 milliliters (mL)/minute (min)/1.73 square meter (m^2) (via Modification of Diet in Renal Disease [MDRD] equation).
- The participant 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 participant 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 participant has any clinically significant abnormalities on electrocardiogram (ECG) that are not related to SLE, as determined by the investigator. Participants with stable ECG changes without evidence of active cardiovascular disease may participate at the discretion of the investigator and medical monitor.
- The participant 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 participant 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 participant has a history of a positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab).
- The participant has a known positive history of antibodies to human immunodeficiency virus (HIV) or HIV disease.
- The participant 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 participant has a history of severe allergic reactions to or hypersensitivity to any component of the study drug.
- The participant is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
- The participant 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 participant has a known history of antibodies to CEP-33457.
- The participant is unlikely to comply with the study protocol or is unsuitable for any other reason, as judged by the investigator or medical monitor.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CEP-33457 CEP-33457 Participants will receive 200 micrograms (mcg) of CEP-33457
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) Baseline up to Week 72 An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included clinically significant vitals, labs, and physical examination findings. Serious adverse events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants Who Received Concomitant Medications Baseline up to Week 72 Any concomitant therapy or medication taken while the participant received study drug.
- Secondary Outcome Measures
Name Time Method Number of Participants Achieving a Clinical Response Using the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72 An SRI response was defined as a reduction from baseline in SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥4 points, no worsening in Physician Global Assessment (PhGA), no new British Isles Lupus Assessment Group (BILAG) A body system score, and ≤1 new BILAG B body system score from baseline. SLEDAI 2K includes 24 weighted clinical and laboratory variables. Total score = 0 to 105. A score of 6 to 10 = moderate disease activity, and a reduction of \>3 points = improvement. PhGA was completed by physician using a visual analog scale (VAS) from 0=none to 3=severe. A change of \>0.3 points = worsening. BILAG includes 97 clinical and laboratory items. Each organ system is assigned a score displayed as a grade from A to E: A=very active disease; B=participant needs increase in treatment for moderately active disease; C=stable or mild disease; D=previous organ involvement but no current disease activity; and E=no current disease activity and organ system has never been involved.
Number of Participants With Anti-nuclear Antibodies (ANA) Week 12, 24, 36, 48, 60, and Final Assessment (or Early Termination [up to Week 72]) Anti-nuclear antibodies (ANA) were measured from blood serum samples at specified time points.
Number of Participants With Mild to Moderate Flare, Severe Flare, and No Flare, Based on the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) Flare Index Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and Final Assessment (or Early Termination [up to Week 72]) The SELENA Flare Index divides flares into 2 categories: mild/moderate and severe. A severe flare would lead to early withdrawal. The number of participants with mild to moderate flare, severe flare, and no flare at each visit during the treatment period were reported.
Number of Participants With British Isles Lupus Assessment Group 2004 (BILAG-2004) Response Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72 The BILAG-2004 is a validated objective and subjective global measure of the SLE disease activity, based on the physician's intention to treat, and refers to disease activity within the last 4 weeks before completion of the index. It includes 97 clinical and laboratory components to evaluate SLE disease activity in 9 different body systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematological). Each body system is assigned a score displayed as a grade from A to E, as follows: A=very active disease; B=participant needs increase in treatment for moderately active disease; C=stab1e or mild disease; D=previous system involvement but no current disease activity; and E=no current disease activity and the body system has never been involved. BILAG 2004 response was defined as no new BILAG A body system score and no more than 1 new BILAG B body system score from baseline.
Number of Participants With Reactive and Non-Reactive Anti-CEP-33457 Antibodies Week 24, 48 and Final Assessment (or Early Termination [up to Week 72]) Immunogenicity was assessed by detection of the presence of specific anti-CEP-33457 antibodies in blood serum samples collected at the specified time points.
Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Total Score Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and Final Assessment (or Early Termination [up to Week 72]) The SLEDAI-2K is a validated objective measure that assesses disease activity within the last 28 days before completion of the index. It is a global index and includes 24 weighted clinical and laboratory variables. The total score (sum of all 24 scores) ranges from 0 to 105, with higher scores representing increased disease activity.
Number of Participants Showing No Worsening on Physician's Global Assessment (PhGA) Scale Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72 The PhGA was completed by the physician using a 3-inch visual analog scale (VAS) labeled from 0=none to 3=severe. A change of greater than 0.3 point on the VAS indicates worsening. The number of participants showing no worsening are presented.
Change From Baseline in Short-Form 36 (SF-36) Domain Scores Baseline, Week 12, 24, 36, 48, 60 and final assessment (or early termination [up to Week 72]) The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, 2) physical role functioning, 3) bodily pain, 4) general health, 5) vitality, 6) social functioning, 7) emotional role functioning, and 8) mental health. All domains are scored on a scale from 0 (worst) to 100 (best), with higher scores representing the best possible health state. Change from baseline scores in the following individual standardized domains: Bodily pain, physical functioning, social functioning and vitality were presented.
Change From Baseline in the Biomarker: Anti-U1 Ribonucleoprotein Antibody (Anti-UI RNP Ab) Baseline, Week 12, 24, 36, 48, 60 and final assessment (or early termination [up to Week 72]) Anti-UI RNP Ab was measured from blood serum collected at specified time points.
Number of Participants Showing No Worsening on Patient's Global Assessment (PtGA) Scale Week 12, 24, 36, 48, 60, and 72 The PtGA was completed by the participant, using a 3-inch VAS labeled from 0=none to 3=severe. A change of greater than 0.3 point on the VAS indicated worsening. The number of participants showing no worsening are presented.
Change From Baseline in the Biomarker: C-Reactive Protein (CRP) Baseline, Week 12, 24, 36, 48, 60, and Final Assessment (or Early Termination [up to Week 72]) CRP was measured from blood serum samples at specified time points.
Number of Participants With Change in Steroid Dose From Baseline up to Final Assessment (or Early Termination [up to Week 72]) Number of participants with change in steroid dose (prednisone equivalent/day) were reported. The change in steroid dose was evaluated to determine the number of participants taking a dose less than 7.5 mg of prednisone equivalent/day, a dose of 7.5 mg prednisone equivalent/day or more, and none per day.
Change From Baseline in Total Damage Score as Assessed by the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Baseline, Week 24, 48 and Final Assessment (or Early Termination [up to Week 72]) The SLICC/ACR damage index assesses specific comorbidities associated with SLE. It consists of 41 items and covers 12 body systems. Total damage scores were calculated using the 41 items. The total damage score ranges from 0 (no damage) to 47 (maximum disease damage severity) with higher scores indicating increasing disease damage severity.
Number of Participants Achieving Remission of Disease Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and Final Assessment (or Early Termination [up to Week 72]) Remission of disease was defined as a reduction of SLEDAI-2K score to 0. The SLEDAI-2K is a validated objective measure that assesses disease activity within the last 28 days before completion of the index. It is a global index and includes 24 weighted clinical and laboratory variables. The total score (sum of all 24 scores) ranges from 0 to 105, with higher scores representing increased disease activity.
Trial Locations
- Locations (85)
Teva Investigational Site 16
🇺🇸Los Angeles, California, United States
Teva Investigational Site 31
🇺🇸Atlanta, Georgia, United States
Teva Investigational Site 29
🇺🇸Dallas, Texas, United States
Teva Investigational Site 5
🇺🇸Los Angeles, California, United States
Teva Investigational Site 10
🇺🇸Boston, Massachusetts, United States
Teva Investigational Site 8
🇺🇸Atlanta, Georgia, United States
Teva Investigational Site 9
🇺🇸Manhasset, New York, United States
Teva Investigational Site 26
🇺🇸Pittsburgh, Pennsylvania, United States
Teva Investigational Site 20
🇺🇸Tucson, Arizona, United States
Teva Investigational Site 4
🇺🇸Aventura, Florida, United States
Teva Investigational Site 600
🇵🇱Elblag, Poland
Teva Investigational Site 32
🇺🇸Clearwater, Florida, United States
Teva Investigational Site 35
🇺🇸Fort Lauderdale, Florida, United States
Teva Investigational Site 1
🇺🇸Jupiter, Florida, United States
Teva Investigational Site 501
🇭🇺Budapest, Hungary
Teva Investigational Site 604
🇵🇱Lublin, Poland
Teva Investigational Site 601
🇵🇱Lublin, Poland
Teva Investigational Site 902
🇺🇦Kyiv, Ukraine
Teva Investigational Site 202
🇨🇿Prague 2, Czechia
Teva Investigational Site 903
🇺🇦Kyiv, Ukraine
Teva Investigational Site 802
🇬🇧Newcastle Upon Tyne, United Kingdom
Teva Investigational Site 27
🇺🇸Birmingham, Alabama, United States
Teva Investigational Site 14
🇺🇸San Leandro, California, United States
Teva Investigational Site 18
🇺🇸Durham, North Carolina, United States
Teva Investigational Site 11
🇺🇸Tampa, Florida, United States
Teva Investigational Site 34
🇺🇸San Antonio, Texas, United States
Teva Investigational Site 21
🇺🇸Oklahoma City, Oklahoma, United States
Teva Investigational Site 30
🇺🇸Aurora, Colorado, United States
Teva Investigational Site 7
🇺🇸San Diego, California, United States
Teva Investigational Site 17
🇺🇸Stanford, California, United States
Teva Investigational Site 38
🇺🇸Stockbridge, Georgia, United States
Teva Investigational Site 23
🇺🇸Coeur d'Alene, Idaho, United States
Teva Investigational Site 37
🇺🇸Lexington, Kentucky, United States
Teva Investigational Site 36
🇺🇸Baltimore, Maryland, United States
Teva Investigational Site 22
🇺🇸Ann Arbor, Michigan, United States
Teva Investigational Site 28
🇺🇸Charlotte, North Carolina, United States
Teva Investigational Site 3
🇺🇸Chapel Hill, North Carolina, United States
Teva Investigational Site 15
🇺🇸Charleston, South Carolina, United States
Teva Investigational Site 25
🇺🇸Duncansville, Pennsylvania, United States
Teva Investigational Site 2
🇺🇸Monroe, North Carolina, United States
Teva Investigational Site 40
🇺🇸Houston, Texas, United States
Teva Investigational Site 6
🇺🇸Houston, Texas, United States
Teva Investigational Site 39
🇺🇸Mesquite, Texas, United States
Teva Investigational Site 24
🇺🇸Temple, Texas, United States
Teva Investigational Site 19
🇺🇸Arlington, Virginia, United States
Teva Investigational Site 12
🇺🇸Seattle, Washington, United States
Teva Investigational Site 102
🇧🇪Brussel, Belgium
Teva Investigational Site 33
🇺🇸Milwaukee, Wisconsin, United States
Teva Investigational Site 101
🇧🇪Liege, Belgium
Teva Investigational Site 100
🇧🇪Yvoir, Belgium
Teva Investigational Site 201
🇨🇿Brno, Czechia
Teva Investigational Site 200
🇨🇿Olomouc, Czechia
Teva Investigational Site 401
🇩🇪Dresden, Germany
Teva Investigational Site 404
🇩🇪Dusseldorf, Germany
Teva Investigational Site 302
🇫🇷Nantes, France
Teva Investigational Site 303
🇫🇷Paris, France
Teva Investigational Site 203
🇨🇿Prague 2, Czechia
Teva Investigational Site 304
🇫🇷Strasbourg, France
Teva Investigational Site 301
🇫🇷Lille, France
Teva Investigational Site 300
🇫🇷Paris, France
Teva Investigational Site 402
🇩🇪Aachen, Germany
Teva Investigational Site 403
🇩🇪Berlin, Germany
Teva Investigational Site 406
🇩🇪Hamburg, Germany
Teva Investigational Site 405
🇩🇪Mainz, Germany
Teva Investigational Site 400
🇩🇪Munchen, Germany
Teva Investigational Site 502
🇭🇺Debrecen, Hungary
Teva Investigational Site 500
🇭🇺Zalaegerszeg, Hungary
Teva Investigational Site 603
🇵🇱Dabrowka, Poland
Teva Investigational Site 602
🇵🇱Konskie, Poland
Teva Investigational Site 606
🇵🇱Warszawa, Poland
Teva Investigational Site 605
🇵🇱Wroclaw, Poland
Teva Investigational Site 701
🇵🇹Amadora, Portugal
Teva Investigational Site 703
🇵🇹Porto, Portugal
Teva Investigational Site 700
🇵🇹Porto, Portugal
Teva Investigational Site 702
🇵🇹Coimbra, Portugal
Teva Investigational Site 751
🇪🇸Dresden, Spain
Teva Investigational Site 752
🇪🇸Santander, Spain
Teva Investigational Site 750
🇪🇸Sevilla, Spain
Teva Investigational Site 901
🇺🇦Donetsk, Ukraine
Teva Investigational Site 900
🇺🇦Kyiv, Ukraine
Teva Investigational Site 905
🇺🇦Ivano-Frankivsk, Ukraine
Teva Investigational Site 904
🇺🇦Lviv, Ukraine
Teva Investigational Site 803
🇬🇧Bath, United Kingdom
Teva Investigational Site 801
🇬🇧Leeds, United Kingdom
Teva Investigational Site 800
🇬🇧London, United Kingdom