Clinical trial NCT01135459: A Study to Evaluate the Efficacy and Safety of CEP-33457 in Participants With Systemic Lupus Erythematosus (SLE)
Official title: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a 200-mcg Dose of CEP-33457 in Patients With Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: Lupus
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2010-06-02
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy of a 200 micrograms (mcg) dose of CEP-33457 compared with placebo in participants with active systemic lupus erythematosus (SLE) as assessed by the proportion of participants achieving a combined clinical response using the SLE responder index (SRI) at Week 24.

Detailed description: The study consisted of a 2-week screening period (visit 1), a 20-week treatment period beginning with a baseline visit in which randomization was completed and study drug treatment began (visits 2 through 7), and a final assessment was performed 4 weeks after the last dose of study drug (visit 8 \[week 24 or early termination\]). Participants were randomized to receive either CEP-33457 or placebo subcutaneously (SC) every 4 weeks. Plasma samples for measurement of study drug concentration were collected in a subset of participants and study drug was administered at each study visit until the final visit. The dose of background steroid medication may have been increased, if needed, to treat the participant for minor fluctuations in lupus disease activity. One interim analysis was conducted when at least 80 participants completed Week 12 or had been withdrawn from the study. Participants who completed the treatment period returned to the study center 4 weeks after the last dose had been administered for final procedures and assessments. Final procedures and assessments for participants who withdrew from the study before 20 weeks of treatment were performed at the last visit. Final procedures and assessments for participants who participated in the study beyond week 24 were to be performed at the next regularly scheduled visit. Participants who complete the study will be eligible for participation in the 12-month open-label study (study C33457/3075; herein referred to as study 3075) to assess continued effectiveness and safety of the CEP-33457 treatment.

Eligibility criteria: Inclusion Criteria:

* The participant 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 participant has a positive test for antinuclear antibody (ANA) at screening and/or a positive test for anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA Ab) at screening.
* 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 a clinical SLEDAI-2K score of at least 6 points during screening.
* The participant does not have an "A" score on the BILAG-2004 scale.
* 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 first dose of study drug.
* If the participant is using antimalarials, methotrexate, leflunomide, mycophenolate mofetil, or azathioprine, the start date must be at least 3 months prior to the first dose of study drug, and the daily dose must be stable over the 4 weeks preceding the first dose of study drug.
* If the participant 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 first dose of study drug. For leflunomide, the stop date must be at least 8 weeks before the first dose of study drug, unless an adequate cholestyramine washout has been completed.

Exclusion Criteria:

* The participant has been treated with intramuscular or intravenous (iv) pulse steroids (ie, 250 to 1000 milligrams \[mg\] iv total daily dose of methylprednisolone) within 4 weeks of the first dose of study drug. The use of intra-articular steroids may be allowed after consultation with the medical expert.
* The participant has received tacrolimus, cyclosporine A, or iv immunoglobulins (IVIG) within 3 months of the first dose of study drug.
* The participant has received cyclophosphamide within 12 months prior to the first dose of study drug.
* The participant has been treated for SLE with agents such as fusion proteins, therapeutic proteins, or monoclonal antibodies or antibody fragments, within 12 months of the first dose of study drug.
* The participant 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).
* The participant has New York Heart Association (NYHA) Class III or IV congestive heart failure.
* The participant has severe active lupus nephritis or cerebritis.
* 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. Participant 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 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 first dose of study drug.
* The participant has a positive test result for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C (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 or has current substance abuse.
* The participant has a history of severe allergic reactions to or hypersensitivity to any component of the study drug or placebo.
* 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.
* The participant has previously participated in a Cephalon- or ImmuPharma-sponsored clinical study with CEP-33457.
* The participant is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
* 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.

Primary outcomes:
measure: Number of Participants Achieving a Combined Clinical Response Using the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Number of Participants Achieving an SRI Response at Each Visit During the Treatment Period
timeFrame: Weeks 4, 8, 12, 16, and 20
measure: Number of Participants Achieving a Reduction of at Least 4 Points in the SLEDAI-2K Total Score
timeFrame: Week 24
measure: Number of Participants Achieving a British Isles Lupus Assessment Group (BILAG) 2004 Response
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: Number of Participants Achieving a BILAG 2004 Clinical Response
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: Number of Participants Achieving a Physician Global Assessment (PhGA) Response
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: Number of Participants Achieving a Patient's Global Assessment (PtGA) Response
timeFrame: Weeks 4, 8, 12, 16, 20, and 24
measure: Change From Baseline in the Medical Outcome Survey Short-Form 36 (SF-36) Patient-Reported Questionnaire For Physical Component Summary (PCS) Score at Weeks 12 and 24
timeFrame: Baseline, Week 12, Week 24
measure: Change From Baseline in the Medical Outcome Survey SF-36 Patient-Reported Questionnaire For Mental Component Summary (MCS) Score at Weeks 12 and 24
timeFrame: Baseline, Week 12, Week 24
measure: Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index
timeFrame: Baseline, Week 24
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 27
state: Alabama
city: Tucson
country: United States
facility: Teva Investigational Site 20
state: Arizona
city: Los Angeles
country: United States
facility: Teva Investigational Site 16
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 5
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 7
state: California
city: San Leandro
country: United States
facility: Teva Investigational Site 14
state: California
city: Stanford
country: United States
facility: Teva Investigational Site 17
state: California
city: Aurora
country: United States
facility: Teva Investigational Site 30
state: Colorado
city: Aventura
country: United States
facility: Teva Investigational Site 4
state: Florida
city: Clearwater
country: United States
facility: Teva Investigational Site 32
state: Florida
city: Fort Lauderdale
country: United States
facility: Teva Investigational Site 35
state: Florida
city: Jupiter
country: United States
facility: Teva Investigational Site 1
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 11
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 8
state: Georgia
city: Atlanta
country: United States
facility: Teva Investigational Site 31
state: Georgia
city: Stockbridge
country: United States
facility: Teva Investigational Site 38
state: Georgia
city: Coeur d'Alene
country: United States
facility: Teva Investigational Site 23
state: Idaho
city: Lexington
country: United States
facility: Teva Investigational Site 37
state: Kentucky
city: Baltimore
country: United States
facility: Teva Investigational Site 36
state: Maryland
city: Boston
country: United States
facility: Teva Investigational Site 10
state: Massachusetts
city: Ann Arbor
country: United States
facility: Teva Investigational Site 22
state: Michigan
city: Manhasset
country: United States
facility: Teva Investigational Site 9
state: New York
city: Chapel Hill
country: United States
facility: Teva Investigational Site 3
state: North Carolina
city: Charlotte
country: United States
facility: Teva Investigational Site 28
state: North Carolina
city: Durham
country: United States
facility: Teva Investigational Site 18
state: North Carolina
city: Monroe
country: United States
facility: Teva Investigational Site 2
state: North Carolina
city: Oklahoma City
country: United States
facility: Teva Investigational Site 21
state: Oklahoma
city: Oklahoma City
country: United States
facility: Teva Investigational Site 13
state: Oklahoma
city: Duncansville
country: United States
facility: Teva Investigational Site 25
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Teva Investigational Site 26
state: Pennsylvania
city: Charleston
country: United States
facility: Teva Investigational Site 15
state: South Carolina
city: Dallas
country: United States
facility: Teva Investigational Site 29
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 40
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 6
state: Texas
city: Mesquite
country: United States
facility: Teva Investigational Site 39
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 34
state: Texas
city: Temple
country: United States
facility: Teva Investigational Site 24
state: Texas
city: Arlington
country: United States
facility: Teva Investigational Site 19
state: Virginia
city: Seattle
country: United States
facility: Teva Investigational Site 12
state: Washington
city: Milwaukee
country: United States
facility: Teva Investigational Site 33
state: Wisconsin
city: Brussel
country: Belgium
facility: Teva Investigational Site 102
city: Liege
country: Belgium
facility: Teva Investigational Site 101
city: Yvoir
country: Belgium
facility: Teva Investigational Site 100
city: Brno
country: Czechia
facility: Teva Investigational Site 201
city: Olomouc
country: Czechia
facility: Teva Investigational Site 200
city: Prague 2
country: Czechia
facility: Teva Investigational Site 202
city: Prague 2
country: Czechia
facility: Teva Investigational Site 203
city: Lille
country: France
facility: Teva Investigational Site 301
city: Nantes
country: France
facility: Teva Investigational Site 302
city: Paris
country: France
facility: Teva Investigational Site 300
city: Paris
country: France
facility: Teva Investigational Site 303
city: Strasbourg
country: France
facility: Teva Investigational Site 304
city: Aachen
country: Germany
facility: Teva Investigational Site 402
city: Berlin
country: Germany
facility: Teva Investigational Site 403
city: Dresden
country: Germany
facility: Teva Investigational Site 401
city: Dusseldorf
country: Germany
facility: Teva Investigational Site 404
city: Hamburg
country: Germany
facility: Teva Investigational Site 406
city: Mainz
country: Germany
facility: Teva Investigational Site 405
city: Munchen
country: Germany
facility: Teva Investigational Site 400
city: Budapest
country: Hungary
facility: Teva Investigational Site 501
city: Debrecen
country: Hungary
facility: Teva Investigational Site 502
city: Zalaegerszeg
country: Hungary
facility: Teva Investigational Site 500
city: Dabrowka
country: Poland
facility: Teva Investigational Site 603
city: Elblag
country: Poland
facility: Teva Investigational Site 600
city: Konskie
country: Poland
facility: Teva Investigational Site 602
city: Lublin
country: Poland
facility: Teva Investigational Site 604
city: Lublin
country: Poland
facility: Teva Investigational Site 601
city: Warszawa
country: Poland
facility: Teva Investigational Site 606
city: Wroclaw
country: Poland
facility: Teva Investigational Site 605
city: Amadora
country: Portugal
facility: Teva Investigational Site 701
city: Coimbra
country: Portugal
facility: Teva Investigational Site 702
city: Porto
country: Portugal
facility: Teva Investigational Site 703
city: Porto
country: Portugal
facility: Teva Investigational Site 700
city: Dresden
country: Spain
facility: Teva Investigational Site 751
city: Santander
country: Spain
facility: Teva Investigational Site 752
city: Sevilla
country: Spain
facility: Teva Investigational Site 750
city: Donetsk
country: Ukraine
facility: Teva Investigational Site 901
city: Ivano-Frankivsk
country: Ukraine
facility: Teva Investigational Site 905
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 900
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 902
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 903
city: Lviv
country: Ukraine
facility: Teva Investigational Site 904
city: Bath
country: United Kingdom
facility: Teva Investigational Site 803
city: Leeds
country: United Kingdom
facility: Teva Investigational Site 801
city: London
country: United Kingdom
facility: Teva Investigational Site 800
city: Newcastle Upon Tyne
country: United Kingdom
facility: Teva Investigational Site 802
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert
role: STUDY_DIRECTOR
References: