A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Subcutaneous LY2127399 in Patients with Systemic Lupus Erythematosus (SLE) (ILLUMINATE-1)
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallelgroup,outpatient study examining the effect of subcutaneous LY2127399 240-mg loading dose followed by 120 mg every 4 weeks and Y2127399 240-mg loading dose followed by 120 mg every 2 weeks (Q2W) versus placebo administered Q2W for 52 weeks in patients with active systemic lupus erythematosus (SLE) who may be receiving concomitant standard of care.
Approximately 1140 patients will be randomized 1:1:1 to 1 of 2 dose groups of LY2127399 or placebo (approximately 380 per treatment group). Patients will be stratified at randomization according to antidsDNA antibody status (positive or negative). For all treatment groups, each patient will receive a loading dose of blinded study drug administered subcutaneously at Week 0. Starting at Week 2, patients will receive blinded study drug administered subcutaneously Q2W through Week 50 (see table below). An additional 2 weeks after the last injection at Week 50 for all treatment arms is considered part of the [Double Quote]52-week[Double Quote] Treatment Period.
Dose Administration by Treatment Group:
For Treatment Group LY 120 mg Q4W (n=380): Loading Dose at Week 0 is 240 mg SC, Dose at Weeks 2 through 50 is Placebo SC Q4W (starting at Week 2) alternating with 120 mg SC Q4W (starting at Week 4)
For treatment group LY 120 mg Q2W (n=380): Loading Dose at Week 0 is 240 mg SC, Dose at Weeks 2 through 50 is 120 mg SC Q2W (starting at Week 2)
For treatment group Placebo (n=380) Loading Dose at Week 0 is Placebo SC, Dose at Weeks 2 through 50 is Placebo SC Q2W (starting at Week 2)
Abbreviations: LY = LY2127399; n = number of patients; Q2W = every 2 weeks; Q4W = every
4 weeks; SC = subcutaneous.
Concomitant SoC in this study can include corticosteroids, non-steroidal anti-inflammatory drugs
(NSAIDs), antimalarials, and immunosuppressants. Doses of antimalarials and immunosuppressants must
not have been adjusted for at least 30 days prior to baseline and should not be adjusted during the
Treatment Period. Adjustments in corticosteroid dose (reductions or increases) will be permitted until
Week 24. Patients receiving and gt;7.5 mg/day prednisone or equivalent at baseline must be receiving a dose
less than or equal to their baseline dose by Week 24. Reductions in corticosteroid dose will be allowed at
any time. Additionally, beyond Week 24, investigators are encouraged to taper the dose of corticosteroids
for patients still receiving and gt;7.5 mg/day prednisone or equivalent to one that is less than their baseline by
Week 52, consistent with clinical practice.
Eligible patients will be offered the opportunity to participate in a separate open-label extension (OLE)
trial, Study H9B-MC-BCDX (BCDX), at Week 52.
All patients not entering the OLE trial (Study BCDX) at Week 52 or who discontinue study treatment at
any time during the study will be followed for safety for at least an additional 24 weeks after the date of
their final injection of study drug. If a patient[Right Quote]s B cell counts have not recovered, additional visits may be
scheduled to continue monitoring the status of B cell counts.
Main Inclusion Criteria:
 Are males or females >=18 years of age.
 Have a clinical diagnosis of SLE defined as meeting 4 of the 11 American College of Rheumatology (ACR) criteria.
 Have a positive ANA (HEp-2 ANA titer >=1:80) as assessed by a central laboratory at
screening. Patients with a negative ANA test result but positive anti-dsDNA test result at
screening will have ANA repeated 1 time during the Screening Period. If the repeat ANA is also
negative, the patient will be excluded from the study.
 Have a screening SELENA-SLEDAI score >=6. (The patient must be actively exhibiting all
the symptoms scored on the screening SELENA-SLEDAI on the day of screening.)
[5a] For female patients of childbearing potential, must test negative for pregnancy at the time of enrollment and agree to use a reliable method of birth control or remain abstinent during the study or for at least 8 weeks following the last dose of study drug, whichever is longer or
[5b] For female patients of non child-bearing potential, defined as: women who have had surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation), women > or = 60 years of age, or women > or = 40 and < 60 years of age who have had a cessation of menses for at least 12 months and a follicle stimulating hormone (FSH) test confirming non childbearing potential (FSH > or = 40mIU/ml)
 Have given written informed consent approved by Lilly or its designee and the IRB/ERB governing the site