A Long-Term Study of the Safety and Tolerability of Repeated Administration of CEP-33457 in Participants 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 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).

Study Overview

• Status: Terminated
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: CEP-33457

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1090
    • Teva Investigational Site 102
  • Liege, Belgium, 4000
    • Teva Investigational Site 101
  • Yvoir, Belgium, 5530
    • Teva Investigational Site 100
• Czechia
  • Brno, Czechia, 638 00
    • Teva Investigational Site 201
  • Olomouc, Czechia, 775 20
    • Teva Investigational Site 200
  • Prague 2, Czechia, 128 08
    • Teva Investigational Site 202
  • Prague 2, Czechia, 128 50
    • Teva Investigational Site 203
• France
  • Lille, France, 59000
    • Teva Investigational Site 301
  • Nantes, France, 44093
    • Teva Investigational Site 302
  • Paris, France, 75013
    • Teva Investigational Site 300
  • Paris, France, 75674
    • Teva Investigational Site 303
  • Strasbourg, France, 67098
    • Teva Investigational Site 304
• Germany
  • Aachen, Germany, 52074
    • Teva Investigational Site 402
  • Berlin, Germany, 12200
    • Teva Investigational Site 403
  • Dresden, Germany, 01307
    • Teva Investigational Site 401
  • Dusseldorf, Germany, 40225
    • Teva Investigational Site 404
  • Hamburg, Germany, 22081
    • Teva Investigational Site 406
  • Mainz, Germany, 55131
    • Teva Investigational Site 405
  • Munchen, Germany, 80336
    • Teva Investigational Site 400
• Hungary
  • Budapest, Hungary, 1023
    • Teva Investigational Site 501
  • Debrecen, Hungary, 4032
    • Teva Investigational Site 502
  • Zalaegerszeg, Hungary, 8900
    • Teva Investigational Site 500
• Poland
  • Dabrowka, Poland, 62-069
    • Teva Investigational Site 603
  • Elblag, Poland, 82-300
    • Teva Investigational Site 600
  • Konskie, Poland, 26-200
    • Teva Investigational Site 602
  • Lublin, Poland, 20-090
    • Teva Investigational Site 604
  • Lublin, Poland, 20-607
    • Teva Investigational Site 601
  • Warszawa, Poland, 00-235
    • Teva Investigational Site 606
  • Wroclaw, Poland, 50-556
    • Teva Investigational Site 605
• Portugal
  • Amadora, Portugal, 2720-276
    • Teva Investigational Site 701
  • Coimbra, Portugal, 3000-075
    • Teva Investigational Site 702
  • Porto, Portugal, 4099-001
    • Teva Investigational Site 703
  • Porto, Portugal, 4200-319
    • Teva Investigational Site 700
• Spain
  • Dresden, Spain, 01307
    • Teva Investigational Site 751
  • Santander, Spain, 39008
    • Teva Investigational Site 752
  • Sevilla, Spain, 41013
    • Teva Investigational Site 750
• Ukraine
  • Donetsk, Ukraine, 83059
    • Teva Investigational Site 901
  • Ivano-Frankivsk, Ukraine, 76018
    • Teva Investigational Site 905
  • Kyiv, Ukraine, 01601
    • Teva Investigational Site 900
  • Kyiv, Ukraine, 03151
    • Teva Investigational Site 902
  • Kyiv, Ukraine, 04107
    • Teva Investigational Site 903
  • Lviv, Ukraine, 79035
    • Teva Investigational Site 904
• United Kingdom
  • Bath, United Kingdom, BA1 1RL
    • Teva Investigational Site 803
  • Leeds, United Kingdom, LS7 4SA
    • Teva Investigational Site 801
  • London, United Kingdom, SE1 7EH
    • Teva Investigational Site 800
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Teva Investigational Site 802
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Teva Investigational Site 27
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Teva Investigational Site 20
  • California
    • Los Angeles, California, United States, 90048
      • Teva Investigational Site 16
    • Los Angeles, California, United States, 90095-1769
      • Teva Investigational Site 5
    • San Diego, California, United States, 92161
      • Teva Investigational Site 7
    • San Leandro, California, United States, 94578
      • Teva Investigational Site 14
    • Stanford, California, United States, 94305
      • Teva Investigational Site 17
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Teva Investigational Site 30
  • Florida
    • Aventura, Florida, United States, 33180
      • Teva Investigational Site 4
    • Clearwater, Florida, United States, 33765
      • Teva Investigational Site 32
    • Fort Lauderdale, Florida, United States, 33334
      • Teva Investigational Site 35
    • Jupiter, Florida, United States, 33458
      • Teva Investigational Site 1
    • Tampa, Florida, United States, 33614
      • Teva Investigational Site 11
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Teva Investigational Site 8
    • Atlanta, Georgia, United States, 30342
      • Teva Investigational Site 31
    • Stockbridge, Georgia, United States, 30281
      • Teva Investigational Site 38
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Teva Investigational Site 23
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Teva Investigational Site 37
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Teva Investigational Site 36
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Teva Investigational Site 10
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Teva Investigational Site 22
  • New York
    • Manhasset, New York, United States, 11030
      • Teva Investigational Site 9
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7600
      • Teva Investigational Site 3
    • Charlotte, North Carolina, United States, 28210
      • Teva Investigational Site 28
    • Durham, North Carolina, United States, 27710
      • Teva Investigational Site 18
    • Monroe, North Carolina, United States, 28112
      • Teva Investigational Site 2
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Teva Investigational Site 21
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Teva Investigational Site 25
    • Pittsburgh, Pennsylvania, United States, 15213
      • Teva Investigational Site 26
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Teva Investigational Site 15
  • Texas
    • Dallas, Texas, United States, 75231
      • Teva Investigational Site 29
    • Houston, Texas, United States, 77034
      • Teva Investigational Site 40
    • Houston, Texas, United States, 77074
      • Teva Investigational Site 6
    • Mesquite, Texas, United States, 75150
      • Teva Investigational Site 39
    • San Antonio, Texas, United States, 78229
      • Teva Investigational Site 34
    • Temple, Texas, United States, 76508
      • Teva Investigational Site 24
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Teva Investigational Site 19
  • Washington
    • Seattle, Washington, United States, 98104
      • Teva Investigational Site 12
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Teva Investigational Site 33

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CEP-33457; Participants will receive 200 micrograms (mcg) of CEP-33457	Drug: CEP-33457; CEP-33457 will be administered subcutaneously per dose specified in the arm description.; Other Names: Lupuzor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	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.	Baseline up to Week 72
Number of Participants Who Received Concomitant Medications	Any concomitant therapy or medication taken while the participant received study drug.	Baseline up to Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving a Clinical Response Using the Systemic Lupus Erythematosus (SLE) Responder Index (SRI)	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.	Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72
Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Total Score	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.	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])
Number of Participants With British Isles Lupus Assessment Group 2004 (BILAG-2004) Response	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.	Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72
Number of Participants Showing No Worsening on Physician's Global Assessment (PhGA) Scale	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.	Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68 and 72
Number of Participants Showing No Worsening on Patient's Global Assessment (PtGA) Scale	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.	Week 12, 24, 36, 48, 60, and 72
Change From Baseline in Short-Form 36 (SF-36) Domain Scores	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.	Baseline, Week 12, 24, 36, 48, 60 and final assessment (or early termination [up to Week 72])
Change From Baseline in the Biomarker: Anti-U1 Ribonucleoprotein Antibody (Anti-UI RNP Ab)	Anti-UI RNP Ab was measured from blood serum collected at specified time points.	Baseline, Week 12, 24, 36, 48, 60 and final assessment (or early termination [up to Week 72])
Change From Baseline in the Biomarker: C-Reactive Protein (CRP)	CRP was measured from blood serum samples at specified time points.	Baseline, Week 12, 24, 36, 48, 60, and Final Assessment (or Early Termination [up to Week 72])
Number of Participants With Anti-nuclear Antibodies (ANA)	Anti-nuclear antibodies (ANA) were measured from blood serum samples at specified time points.	Week 12, 24, 36, 48, 60, and Final Assessment (or Early Termination [up to Week 72])
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	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.	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])
Change From Baseline in Total Damage Score as Assessed by the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index	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.	Baseline, Week 24, 48 and Final Assessment (or Early Termination [up to Week 72])
Number of Participants Achieving Remission of Disease	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.	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])
Number of Participants With Change in Steroid Dose	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.	From Baseline up to Final Assessment (or Early Termination [up to Week 72])
Number of Participants With Reactive and Non-Reactive Anti-CEP-33457 Antibodies	Immunogenicity was assessed by detection of the presence of specific anti-CEP-33457 antibodies in blood serum samples collected at the specified time points.	Week 24, 48 and Final Assessment (or Early Termination [up to Week 72])

Collaborators and Investigators

• Sponsor: Cephalon, Inc.
• Investigators: Study Director: Teva Medical Expert, Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2010
• Primary Completion (Actual): June 14, 2012
• Study Completion (Actual): June 14, 2012

Study Registration Dates

• First Submitted: October 15, 2010
• First Submitted That Met QC Criteria: November 12, 2010
• First Posted (Estimate): November 15, 2010

Study Record Updates

• Last Update Posted (Actual): December 30, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Lupus; SLE
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: C33457/3075