None listed
Conditions
Brief summary
This is a Phase 3, multicenter, placebo-controlled, randomized, double-blind study to evaluate the efficacy, safety, tolerability, and immunogenicity of epratuzumab in subjects with moderate to severe general systemic lupus erythematosus (SLE). The study population consists of subjects (>=18 years of age) receiving a stable dose of corticosteroids (5 to 60mg/day prednisone equivalents) for at least 5 days (±1 day) prior to Week 0 (Visit 2) and the first dose of study drug. Subjects must have a diagnosis of SLE by the American College of Rheumatology (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). In addition, subjects must have British Isles Lupus Assessment Group (BILAG) Index (version 2004) level A disease activity in at least 1 body/organ system, or BILAG level B disease activity in at least 2 body/organ systems at Baseline among the BILAG-defined mucocutaneous, musculoskeletal, or cardiorespiratory body systems, and active moderate to severe SLE disease activity as demonstrated by a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) total score of at least 6. Approximately 1053 subjects will be enrolled to randomize 780 subjects in this study. For each subject, the study will last a maximum of 54 weeks and will consist of a Screening Period (1 to 14 days), a double-blind Treatment Period consisting of four 12-week treatment cycles (48 weeks total), and a Safety Follow-Up Visit for subjects not participating in the open-label extension study, SL0012, at 13 weeks from their final dose of study drug, or a maximum of 4 weeks beyond Week 48 (ie, no later than Week 52). Eligible subjects will be randomized in a 1:1:1 ratio as follows: Epratuzumab 600mg infusions delivered once a week (QW) for a total of 4 weeks (cumulative dose [CMD] 2400mg) over four 12-week treatment cycles (ie, Weeks 0, 1, 2, 3, 12, 13, 14, 15, 24, 25, 26, 27, 36, 37, 38, and 39) Epratuzumab 1200mg infusions delivered every other week (QOW) for a total of 4 weeks (CMD 2400mg) over four 12-week treatment cycles (ie, Weeks 0, 2, 12, 14, 24, 26, 36, and38); and placebo (PBO) infusions delivered QOW for a total of 4 weeks over four 12-week treatment cycles (ie, Weeks 1, 3, 13, 15, 25, 27, 37, and 39) PBO infusions delivered QW for a total of 4 weeks over four 12-week treatment cycles (ie, Weeks 0, 1, 2, 3, 12, 13, 14, 15, 24, 25, 26, 27, 36, 37, 38, and 39) The primary objective of the study is to confirm the clinical efficacy of epratuzumab in the treatment of subjects with moderate to severe general SLE despite standard of care treatments (ie, corticosteroids, and potentially antimalarials and immunosuppressants) continued from Baseline. The secondary objectives of the study are to assess the safety, tolerability, and immunogenicity of epratuzumab, and to assess the steroid-sparing effects of epratuzumab treatment. The exploratory objectives of the study are to assess the pharmacokinetics (PK) of epratuzumab; the effects of epratuzumab treatment on individual components of the combined response index, fatigue associated with moderate to severe SLE, and the health-related quality of life (HRQoL) and utility benefits of epratuzumab treatment.
Interventions
Arm 1 – Epratuzumab 600 mg infusions delivered weekly for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles
Arm 2 – Epratuzumab 1200 mg infusions delivered every other week for a total of 4 weeks (cumulative dose 2400 mg) over four 12-week treatment cycles and placebo infusions delivered every other week for a total of 4 weeks over four 12-week treatment cycles
Arm 3 – Placebo infusions delivered weekly for a total of 4 weeks over four 12-week treatment cycles
Sponsors
UCB, Inc
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Positive antinuclear antibodies (ANA) at Screening (Visit 1) Current clinical diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria such that at least 4 of the 11 criteria are met Active moderate to severe SLE activity as demonstrated by the British Isles Lupus Assessment Group Index (BILAG) Active moderate to severe SLE disease as demonstrated by SLEDAI total score On stable SLE treatment regimen, including mandatory corticosteroids and immunosuppressants or antimalarials
Exclusion criteria
Subjects who are breastfeeding, pregnant, or plan to become pregnant Subjects with active, severe SLE disease activity which involves the renal system Subjects with active, severe, neuropsychiatric SLE, defined as any neuropsychiatric element scoring BILAG level A disease. Subjects with the evidence of an immunosuppressive state Subjects who, in the opinion of the investigator, are at a particularly high risk of significant infection History of malignant cancer, except the following treated cancers: cervical carcinoma in situ, basal cell carcinoma, or dermatological squamous cell carcinoma. Subjects receiving any live vaccination within the 8 weeks prior to screening (Visit 1). Subjects with history of infections, including but not limited to concurrent acute or chronic viral hepatitis B or C Subjects with substance abuse or dependence or other relevant concurrent medical condition Subjects with history of thromboembolic events within 1 year of screening Visit. Subjects with significant hematologic abnormalities Subject has received treatment with other anti- B cell antibodies within 12 months prior to screening (visit 1) Subject use of oral anticoagulant (not including) nonsteroidal anti-inflammatory drugs (NSAIDs) within 12 weeks prior to screening (Visit 1) Subject has previously participated in this study or has previously received epratuzumab treatment
Outcome results
None listed