A 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). Revised Protocol 03, incorporating Protocol Amendment 05 (V2.0, dated 08-Feb-2008), Administrative Letter 01 (dated 13-Jun-2007), Protocol Amendment 07 (V1.0, dated 17-Apr-2008), and Protocol Amendment 11 (V1.0, dated 11-Dec-2008). + Pharmacogenetics Blood Sample Amendment Number 1 - Site Specific (V2.0, Date 19-Jan-07). And Protocol Amendment 02 - Site specific (v1.0, date 09-Mar-2007).

Phase 1

• Conditions: IMMUNOSUPPRESSION FOR DISEASE, NOS; MedDRA version: 9.1Level: LLTClassification code 10025139Term: Lupus erythematosus systemic

• Registration Number: EUCTR2005-004575-37-GB
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-10-08
• Study Completion: 2011-08-02
• Last Update Posted: 27 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 460

Inclusion Criteria

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 12 months prior to 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)] or WHO 1982 Classification Class III or IV (excluding
Class III c, IVd). NOTE: If the biopsy was performed > 3 months but = 12 months
prior to screening visit, at least 1 of the following 3 serologies (performed locally)
must be abnormal prior to screening visit:
Complement (C3 or C4) level below normal range
OR
Anti-dsDNA > upper limit of normal range
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
Subjects not meeting all the criteria but meeting all other inclusion and exclusion
criteria may be re-screened for urinary sediment ONCE within 2 weeks of the original
screening visit in consultation with the BMS Medical Monitor.
NOTE: Subjects prior to consenting who were treated with systemic
glucocorticosteroid treatment (at least 30 mg or 0.5 mg/kg of prednisone-equivalent
or intravenous pulse, as per local standards) during the current episode of lupus
nephritis AND had documented abnormal (> ULN) urinary sediment (as per local
laboratory) during the current episode of lupus nephritis AND have persisting
proteinuria (urinary protein/creatinine ratio = 50 mg/mmol) present at screening visit,
will be considered to have met this inclusion criterion.
5) Serum creatinine = 3 mg/dL (i.e., = 265 micromol/L). (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 16 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? yes
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

Exclusion Criteria

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 that require definitive
therapy according to local guidelines or the Consensus Guidelines and have not been
properly treated (refer to Section 7.3.2.4).
14) Subjects with a history of cancer within the last five years (other than non-melanoma
skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers
must be removed prior to randomization (Day 1 treatment). Subjects with carcinoma
in situ, treated with definitive surgical intervention, are allowed.
15) Subjects with any serious bacterial infection within the last 3 months, unless treated
and resolved with antibiotics, or any chronic bacterial infection (such as chronic
pyelonephritis, osteomyelitis and bronchiectasis).
16) Subjects at risk for tuberculosis. Specifically, subjects with:
a) Current clinical, radiographic or laboratory evidence of active TB.
b) A history of active TB within the last 3 years even if it was treated.
c) A history of active TB greater than 3 years ago unless there is documentation that
the prior anti-TB treatment was appropriate in duration and type.
d) Latent TB which has not been successfully treated.
17) Subjects with herpes zoster that resolved less than 2 months prior to screening visit.
18) Subjects with evidence (as assessed by the Investigator) of active or latent bacterial or
viral infections at the time of potential enrollment, including subjects with evidence
of Human Immunodeficiency Virus (HIV) infection.
19) Subjects who are renal transplant recipients or candidates.
20) Subjects who are diagnosed as end-stage renal disease.
21) Subjects with persistent non-lupus related pyuria.
22) Subjects with a degree of tubulo-interstitial

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified