Lupus SLE
Conditions
Interventions
There will be four 12-week treatment cycles. This means that you can be treated
with study drug up to16 times during the course of the study. Your
participation in the study will last approximately
Sponsors
UCB Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. The subject must be at least 18 years old at the Screening Visit (Visit 1). 2. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form/authorization forms (as applicable) are signed and dated by the subject prior to the initiation of any study-specific assessment at Screening (Visit 1). 3. Adequate reading and writing abilities such that the subject can comprehend and answer the questions on the subject-completed assessments. 4. The subject is considered reliable, willing, and capable of adhering to the protocol, and visit schedule, according to the judgment of the investigator. 5. Women of childbearing potential must agree to use an acceptable method of birth control during the study and for a period of 3 months after their final dose of study drug. Acceptable forms of birth control include oral contraceptives (which must be stable for at least 1 full month prior to Screening [Visit 1], and should remain stable during the study), double-barrier methods, and the single-barrier methods of diaphragm with adjunct spermacide or condom with adjunct spermacide. Unacceptable methods include abstinence alone or condoms/diaphragm use without adjunct spermacide. Women not agreeing to use birth control must be surgically sterile (hysterectomy/oophrectomy or tubal ligation) or postmenopausal for at least 2 years prior to Screening (Visit 1). Women of childbearing potential are required to have a serum pregnancy test taken at Screening (Visit 1), which is confirmed to be negative by urine testing prior to the first dose of study drug at Week 0 (Visit 2). 6. The subject has positive results for antinuclear antibodies (ANAs) (titer *1:80) or anti-dsDNA at Screening (Visit 1) at the central laboratory using their testing methodologies. 7. The subject has SLE diagnosed by a physician, as defined by the most recent ACR revised criteria, such that at least 4 (not including Neurologic Disorder) of the 11 criteria are met. If positive for Neurologic Disorder criteria, a total of 5 of the 11 ACR criteria must be met. 8. The subject has active moderate to severe SLE disease activity, as demonstrated by BILAG level A disease activity in at least 1 body/organ system (except renal or neurological), or BILAG level B level disease activity in at least 2 body/organ systems if no BILAG level A disease is present. At least 1 of the BILAG A scores OR at least 2 of the BILAG B scores must be in the following BILAG body/organ systems: mucocutaneous, musculoskeletal, or cardiorespiratory. 9. The subject has active moderate to severe SLE disease activity as demonstrated by a SLEDAI total score of at least 6 at Screening (Visit 1). 10. Subjects receiving antimalarials must have been receiving them for at least 12 weeks prior to Screening/Baseline (Visit 1), with a stable dose regimen for at least 28 days (±1 day) prior to Week 0 (Visit 2) and the;first study drug infusion. 11. Subjects receiving immunosuppressants must be at a stable dose for at least 28 days (±1 day) prior to Visit 2 and the first study drug infusion. 12. Subjects must be receiving corticosteroids within the range of 5 to 60mg/day prednisone equivalents at a stable dose for at least 5 days (±1 day) prior to Week 0 (Visit 2) and the first study drug infusion, with the corticosteroid dose dependent on the investigator*s assessment of disease activity. This excludes the use of high-pulse doses of iv Solu-Medrol®. 13. Subjects receiving memantine, br
Exclusion criteria
Exclusion criteria: 1. The subject has active, severe, neuropsychiatric SLE, defined as any neuropsychiatric element scoring BILAG level A disease, including but not limited to: new or worsening impaired level of consciousness, psychosis, delirium or confusional state, grand mal seizure (including status epilepticus), stroke or stroke syndrome, aseptic meningitis, ascending or transverse myelitis, cranial neuropathy, chorea, cerebellar ataxia, demyelinating syndromes or any other severe neurologic condition which, in the opinion of the investigator, would prevent the subject from completing protocol-required procedures and assessments. Mononeuritis single/multiplex and/or polyneuropathy are NOT exclusionary, even if they result in a CNS BILAG A score, provided they are not new or worsening at Screening (Visit 1). 2. The subject has active, severe, SLE disease activity which involves the renal system (defined by BILAG renal level A activity), serum creatinine >2.5mg/dL, or a clinically significant serum creatinine increase within the 4 weeks prior to Screening (Visit 1), or proteinuria >3.5g/day. 3.Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the study or within 3 months following their final dose of study drug. 4.Evidence of an immunosuppressive state, including HIV infection, agammaglobulinemias, T-cell deficiencies, or HTLV-1. 5.Subjects with a history of chronic infections, including but not limited to subjects with concurrent acute or chronic viral hepatitis B or C. Also excluding subjects with a history of a recent serious or life-threatening infection or any current signs or symptoms that may indicate a significant infection at Screening (Visit 1), as per the investigator*s clinical judgment. Subjects must have completed any prior anti-infective therapy prior to the first dose of study drug with the exception of anti-infectives taken specifically for the treatment of acne, rosacea, onychomycosis, or vaginal yeast infections; for the prophylaxis of urinary tract infections; or prophylaxis for pre-surgical or pre-procedural reasons (including dental procedures). Note: minocycline may not be used for these purposes. 6.Subjects who, in the opinion of the investigator, are at a particularly high risk of significant infection due to their lifestyle and/or occupation. 7.Subjects with substance abuse/dependence or other concurrent medical conditions that could confound study interpretation or affect the subject*s ability to fully participate in the study. 8.Subjects receiving any live (includes attenuated) vaccination within the 8 the 8 weeks prior to Screening (Visit 1) (eg, inactivated influenza and pneumococcal vaccines are allowed but nasal influenza vaccination is not permitted). 9.Spontaneous or induced abortion, still or live birth within 4 weeks prior to Screening (Visit 1). 10. Use of oral anticoagulants (not including NSAIDs) within the 12 weeks prior to Screening (Visit 1). 11. Subject has a history of thromboembolic events (eg, myocardial infarction, cerebrovascular accident, deep vein thrombosis, pulmonary embolism) within 1 year of Screening (Visit 1) or subjects with known anti-phospholipid syndrome (Miyakis et al, 2006). 12. Significant hematologic abnormalities of hemoglobin <8.0 g/dL, or WBC <2000/mm3, or absolute neutrophil count <1500/mm3, or platelets <30,000/mm3 at Screening (Visit 1). 13. History of malignant cancer, except the following treated ca
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy variable is the responder rate at Week 48 according to a combined response index. This is a response variable (yes/no) evaluated at Week 48 incorporating the following criteria for achievement of responder status (ie, all criteria must be met to achieve responder status): * British Isle Lupus Assessment Group improvement, defined as BILAG As at study entry improved to B/C/D, and BILAG Bs at study entry improved to C/D, and no BILAG worsening in other BILAG organ systems such that there are no new BILAG As or greater than 1 new BILAG B(s); and * No worsening in the SLEDAI total score compared to study entry (defined as no increase in SLEDAI total score); and * No worsening in the physicians* global assessment of disease activity (*no worsening* is defined as less than 10% worsening, equivalent to a 10mm increase on a 100mm visual analog scale[VAS]) compared to study entry; and * No changes in concomitant medications according to the following criteria: * No increase of (or addition of a new) immunosuppressant or antimalarial agent over Baseline (Week 0/Visit 2) levels, or initiation of any medication listed in Table 7.4; or * No increase in oral corticosteroid dose greater than 25% over Baseline (Week 0/Visit 2) levels from Week 0 to Week 8 for an SLE-related indication; or * No increase in oral corticosteroids over Baseline (Week 0/Visit 2) levels after Week 8 for an SLE-related indication; or * No iv, intra-articular (ia), or intramuscular (im) injections of corticosteroids which are SLE-related. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Adverse Events * Serious Adverse Events * Laboratory Measurements * Pregnancy Testing * Vital Signs * Body Mass * 12-Lead ECG * Data Safety Monitoring Board | — |
Countries
Netherlands
Outcome results
None listed