A Sequential Adaptive Phase II/III Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept Versus Placebo on a Background of Mycophenolate Mofetil and Glucocorticosteroids in Subjects with Active Proliferative Glomerulonephritis Due to Systemic Lupus Erythematosus (SLE).And Pharmacogenetics Blood Sample Amendment Number 1 - Site Specific (Version 2.0, Date 19-Jan-07).
- Conditions
- IMMUNOSUPPRESSION FOR DISEASE, NOSMedDRA version: 9.1Level: LLTClassification code 10025139Term: Lupus erythematosus systemic
- Registration Number
- EUCTR2005-004575-37-FR
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 460
1) Signed written informed consent
2) SLE as defined by meeting at least 4 of the 11 classification criteria of the American College of Rheumatology for the classification of Systemic Lupus Erythematosus (Protocol Appendix 1), either sequentially or coincidentally. The 4 criteria need not be present at the time of study entry.
3) Biopsy within 6 months of enrollment (screening visit) indicating active proliferative
lupus glomerulonephritis ISN/RPS 2003 classification Class III or IV [excluding Class III (C), IV-S (C) and IV-G (C)]. If renal function has deteriorated, biopsy may have been no more than 3 months prior to enrollment (screening visit).
4) Active renal disease at the screening visit, as defined by:
urinary protein/creatinine ratio = 50 mg/mmol AND an active urinary sediment as defined by at least one of the following 3 criteria:
a) > 5 RBC/hpf OR
b) > 8 WBC/hpf (with no evidence of a urinary tract infection) OR
c) cylindruria
5) Serum creatinine = 3 mg/dL. (Subjects not meeting this criterion but meeting all other inclusion and exclusion criteria may be re-screened for serum creatinine ONCE
within 2 weeks of the original screening visit in consultation with the BMS Medical
Monitor).
6) Men and women, at least 18 years of age.
7) Eligibility of subjects for entry into the study is based on their current renal disease activity which may represent:
a) The first manifestation of their SLE.
b) The first renal manifestation of SLE.
c) Recent worsening of glomerulonephritis that had been diagnosed previously.
d) Persistence of renal disease despite current therapies, including MMF and/or
glucocorticosteroids, as long as the medications used are permitted by protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1)WOCBP unwilling or unable to use an acceptable method to avoid pregnancy for entire study period & up to 10 weeks after study
2)WOCBP using a prohibited contraceptive method (there are none)
3)pregnant or breastfeeding women
4)Women with positive pregnancy test on enrollment or prior to study drug
administration
5)Males unwilling or unable to follow recommendations for use of contraception
specified by the manufacturer of any protocol-permitted disease sparing medication
(biologic or non-biologic) being used during study
6)Subjects with a rise of serum creatinine of = 1 mg/dL within 1 month prior to screening visit
7)Subjects with drug-induced SLE, as opposed to idiopathic SLE.
8)Subjects with severe, unstable &/or progressive CNS lupus (screening MRI or other imaging of the brain is not required to rule-out CNS disease in subjects who have no clinical features suggesting active CNS disease)
9)Subjects with autoimmune disease other than SLE as their main diagnosis (e.g.; RA, MS)
10)Current symptoms of severe, progressive, or uncontrolled non-SLE related renal,
hepatic, hematological, gastrointestinal, pulmonary, cardiovascular, neurological,
endocrine, or cerebral disease. Concomitant medical conditions that, in the opinion of
the Investigator, might place the subject at unacceptable risk for participation in this
study
11)Concomitant illness that in the opinion of the investigator, is likely to require
additional high dose oral glucocorticosteroid therapy (i.e. > 45 mg per day) during study, (e.g.; asthma)
12)Female subjects who have had breast cancer screening study suspicious for malignancy, & in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations
13)Female subjects who have evidence of cervical dysplasia unless treated with
definitive therapy
14)history of cancer within last 5 years (other than non-melanoma skin cell (NMSC) cancers cured by local resection). Existing NMSC cancers must be removed prior to randomization (Day 1 treatment). Subjects with carcinoma in situ, treated with definitive surgical intervention, are allowed
15)any serious bacterial infection within last 3 months, unless treated & resolved with antibiotics, or any chronic bacterial infection (such as chronic pyelonephritis, osteomyelitis & bronchiectasis)
16)Subjects at risk for tuberculosis. Specifically subjects with:
a)Current clinical, radiographic or laboratory evidence of active TB
b)history of active TB within last 3 years even if treated
c)history of active TB > 3 years ago unless there is documentation that
the prior anti-TB treatment was appropriate in duration & type
d)Latent TB which has not been successfully treated
17)Subjects with herpes zoster that resolved < 2 months prior to screening visit
18)Subjects with evidence (as assessed by the Investigator) of active or latent bacterial or viral infections at time of potential enrollment, including subjects with evidence of HIV infection
19)renal transplant recipients or candidates
20)Subjects who are diagnosed as end-stage renal disease
21)persistent non-lupus related pyuria
22)a degree of tubulo-interstitial changes that suggest an irreversible
decrease in renal function
23) Subjects currently on hydroxychloroquine or chloroquine with evidence of
retinopathy within 6 months of screening visit. If local standards for routine
ophthalmologic follow-up suggest such formal examinations are needed subjects who ha
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method