A Study to Evaluate the Efficacy and Safety of CEP-33457 in Patients With Systemic Lupus Erythematosus

• Register: ClinicalTrials.gov
• Last refreshed on: 8 August 2016
• Main ID: NCT01135459
• Date of registration: 01/06/2010
• Prospective Registration: Yes
• Primary sponsor: Cephalon
• Public title: A Study to Evaluate the Efficacy and Safety of CEP-33457 in Patients With Systemic Lupus Erythematosus
• Scientific 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
• Date of first enrolment: June 2010
• Target sample size: 183
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01135459
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Belgium, Czech Republic, France, Germany, Hungary, Poland, Portugal, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Sponsor's Medical Expert
• Affiliation: Cephalon

Key inclusion & exclusion criteria

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 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 patient has a clinical SLEDAI-2K score of at least 6 points during screening.

- The patient 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 patient 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 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 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 patient has been treated with intramuscular or intravenous (iv) pulse steroids
(ie, 250 to 1000 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 patient has received tacrolimus, cyclosporine A, or iv immunoglobulins (IVIG)
within 3 months of the first dose of study drug.

- The patient has received cyclophosphamide within 12 months prior to the first dose of
study drug.

- 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
first dose of study drug.

- 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).

- The patient has New York Heart Association (NYHA) Class III or IV congestive heart
failure.

- The patient has severe active lupus nephritis or cerebritis.

- 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 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 patient has a positive test result for hepatitis B surface antigen (HBsAg) or
antibodies to hepatitis C (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 or has current substance abuse.

- The patient has a history of severe allergic reactions to or hypersensitivity to any
component of the study drug or placebo.

- 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.

- The patient has previously participated in a Cephalon- or ImmuPharma-sponsored
clinical study with CEP-33457.

- The patient is a pregnant or lactating woman. (Any women becoming pregnant during the
study will be withdrawn from the study.)

- 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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: Placebo

Drug: Lupuzor

Primary Outcome(s)

The proportion of patients achieving a combined clinical response using the SLE responder index (SRI) [Time Frame: Baseline and Final Assessment (week 24 or early termination)]

Secondary Outcome(s)

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: Baseline, week 12, and Final Assessment (Week 24 or early termination)]

Effect of CEP-33457 on disease activity, as assessed by the BILAG-2004 disease activity index at each visit during the treatment period [Time Frame: at weeks 4 and final assessment (week 24 or early termination)]

Evaluation of the safety and tolerability of CEP-33457 [Time Frame: At protocol-specified timepoints from screening through Week 24 or early terminiation.]

Proportion of patients achieving an SRI response at each visit during the treatment period [Time Frame: at weeks 4, 8, 12, 16, 20, and 24]

Effect of CEP-33457 on the status of disease (PhGA and Patient's Global Assessment [PtGA] scales) at each visit during the treatment period [Time Frame: at weeks 4, 8, 12, 16, 20, and 24]

Medical Outcome Survey Short Form 36 (SF-36) [Time Frame: At baseline, Weeks 12 and the final assessment (Week 24 or early termination)]

Proportion of patients achieving a reduction of at least 4 points in the SLEDAI-2K total score at the final assessment [Time Frame: Baseline and Final Assessment (Week 24 or early termination)]

Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR) [Time Frame: Assessed at screening and Week 24 or early termination]

Secondary ID(s)

C33457/2047

Source(s) of Monetary Support

Please refer to primary and secondary sponsors