A Phase IIB, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study toEvaluate the Efficacy and Safety of Abatacept vs. Placebo on a Background of OralGlucocorticosteroids in the Treatment of Subjects with Systemic Lupus Erythematosusand the Prevention of Subsequent Lupus Flares.Revised Protocol 1.0 dated 03-June-2005 + Amendment 1 dated 08-Feb-2005

• Conditions: SYSTEMIC LUPUS ERYTHEMATOSUS, NOS

• Registration Number: EUCTR2004-004051-19-GB
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-03-24
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1) Subjects must have SLE as defined by meeting 4 of the 11 classification criteria of
the American College of Rheumatology for the classification of Systemic Lupus
Erythematosus (Appendix 1), either sequentially or coincident. The 4 criteria need not
be present at study entry, but have occurred at some time during the course of the
disease.
2) Within 14 days of the screening visit, subjects must have at least one of the following flare manifestations of SLE, as defined by the BILAG criteria as modified for use in this study. The flare
manifestation may represent the initial activity within that organ system or may be a
recurrence of activity in an organ system previously affected. If the latter is the case,
the organ system now flaring must have been inactive for at least 3 months prior to
the onset of the current flare. (the subject may be experiencing other BILAG A”
or B” features of lupus as well (other than renal or central nervous system
which are specifically excluded from entry), but features other than those
specified below are not sufficient for entry into the study):
a) Active mucocutaneous discoid lesions:
i) A”: severe active facial and/or extensive discoid lesions (> 2/9 of body
surface area), scarring or causing disability recorded as >1.
ii) B”: localized active discoid lesions (< 1/9 total body surface area), including
lupus profundus recorded as >1
The skin lesions must be actively inflamed; they cannot be solely chronic
changes, e.g. scar with depigmentation. In order to satisfy inclusion rules, the
currently active lesions cannot represent ongoing chronic and continuous
activity - they must constitute a flare, either newly inflamed or previously
inflamed but quiescent for at least 3 months.
b) Active polyarthritis:
i) A”: severe polyarthritis recorded as >1 with loss of function (not responsive to steroids less
than 10 mg per day, antimalarials, NSAIDs)
ii) B”: Arthritis recorded as >1: active joint inflammation without loss of functional range of
motion.
At least 3 actively inflamed joints--swollen, tender, erythematous--not
isolated Jaccoud arthropathy although the presence of Jaccoud arthropathy in
a subject with active inflammation will not preclude study entry. The
inflamed joints cannot have been chronically and continuously inflamed- they
must constitute a flare, either newly inflamed or previously inflamed but
quiescent for at least 3 months.
c) Active serositis (pleuritis/pericarditis):
i) A” Symptomatic effusion recorded as >1 plus two other criteria listed below>1 or four of the following criteria listed below each recorded as >1: pleuropericardial pain; dyspnea; friction
rub; chest x-ray revealing pleural or pericardial effusion; electrocardiogram
changes of pericarditis; or cardiac arrhythmia including tachycardia > 100
beats per minute in the absence of fever.
ii) B”: Two of the following criteria listed below each recorded as >1: pleuropericardial pain; dyspnea; friction
rub; chest x-ray revealing pleural or pericardial effusion; electrocardiogram
changes of pericarditis; or cardiac arrhythmia including tachycardia > 100
beats per minute in the absence of fever.
Although commonly used in some practices, echocardiographic confirmation
of the presence of pericardial disease is not considered a BILAG criterion and
therefore cannot be substituted for any of the criteria noted above.
Eligibility of subjects for entry into the study is based on their current disease activity
(flare characteristics).

Exclusion Criteria

1) Women who are pregnant or breast-feeding.
2) Women with a positive pregnancy test on enrollment or prior to study drug
administration.
3) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 10 weeks after the last infusion of study medication.
4) Males unwilling or unable to use an adequate method of contraception for the entire study period and for up to 10 weeks after the last infusion of study medication.
5) Treatment of current SLE flare with corticosteroids for more than 5 days.
6) Active anti-phospholipid antibody syndrome, (i.e. recent untreated thromboses,
cerebral or pulmonary emboli, pregnancy loss, pleurisy due to thromboembolic
phenomena) as the sole or primary feature of their SLE or SLE-like syndrome. Any
subject requiring anti-coagulation, other than low-dose aspirin, for anti-phospholipid
antibody syndrome will be excluded from this study.
7) Subjects with drug-induced SLE, rather than idiopathic” SLE.
8) Subjects with other autoimmune disease as a main diagnosis other than SLE (e.g.;
RA, MS).
9) Current symptoms of severe, progressive, or uncontrolled renal, hepatic,
hematological, gastrointestinal, non-SLE pulmonary, non-SLE cardiac, neurological,
or cerebral disease; pulmonary and/or cardiac manifestations of SLE shall not
constitute an exclusion to study entry. Concomitant medical conditions that, in the
opinion of the Investigator, might place the subject at unacceptable risk for
participation in this study.
10) Concomitant illness that in the opinion of the investigator, is likely to require
additional glucocorticosteroid therapy during the study, (e.g.; asthma).
11) Female subjects with a breast cancer screening that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following
additional clinical, laboratory or other diagnostic evaluations.
12) 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).
13) Subjects who have a history of clinically significant drug or alcohol abuse. Subjects currently taking methotrexate who admit to consumption of more than an average of 1 alcoholic drink per day.
14) Subjects with any serious bacterial infection (such as pneumonia, renal infection and sinusitis), unless treated and resolved with antibiotics or chronic bacterial infection (such as pyelonephritis, osteomyelitis and lung infection with bronchiectasis) in the previous 3 months.
15) Subjects with active tuberculosis (TB) requiring treatment within the previous
3 years. Subjects with a positive PPD at screening will not be eligible for the study
unless they have a negative chest x-ray at enrollment and have completed treatment
for latent TB. A PPD response that is equal to or greater than 10 mm should be
considered a positive test, although more conservative criteria may be applied as
determined by the clinical circumstance and investigator according to published
guidelines and/or local standards endorsed by the medical society.
16) Subjects with herpes zoster that resolved less than 2 months prior to enrollment.
17) 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)

Study & Design

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