1. Systemic Lupus Erythematosus and Active Skin Manifestations2. Active Cutaneous Lupus Erythematosus with or without Systemic Manifestations

The primary objective of the study is to evaluate the efficacy of BIIB059 in reducing skin disease activity in subjects with SLE (Part A), and in subjects with active CLE with or without systemic manifestations (Part B), and to investigate the dose response relationship in subjects with active SLE and skin manifestations (Part A only)

BIIB059

BIIB059

Solution for Injection

150

 The primary endpoint that relates to this objective is
the Week 12 percent change from baseline in
Cutaneous Lupus Erythematosus Disease Area and
Severity Index-Activity (CLASI-A) score

Secondary Objectives and Endpoints
To evaluate additional efficacy parameters of BIIB059 in
reducing SLE disease activity.
The endpoints that relate to this objective are:
Skin related
 CLASI-50 response, defined as a 50% improvement
from baseline in CLASI-A score, at Week 12 (Parts
A and B) and Week 24 (Part A only)
 Percent change from baseline over time in CLASI-A
score
 A ≥ 4-point reduction in CLASI-A score at Week 12
and, for Part A only, Week 24 compared with
baseline
SLE disease activity related (Part A Only)
 Composite endpoint of SLE Responder Index (SRI)
of ≥ 4 (SRI-4) at Week 24 compared with baseline,
with concomitant oral corticosteroid dosage ≤ 10
mg/day and ≤ Day 1, and stable or decreased oral
corticosteroid dose between Weeks 12 and 24.
Composite endpoint SRI-4 is defined as:
 A reduction from baseline of ≥ 4 points in
Systemic Lupus Erythematosus Disease Activity
Index (SLEDAI)-2K AND
 No new organ system affected, as defined by no
new British Isles Lupus Activity Group (BILAG)-
2004 A or ≤ 2B, AND
 No worsening from baseline in subject’s lupus
disease activity defined by ≤ 0.3 point increase
in Physician’s Global Assessment (PGA) visual
analogue scale (VAS) AND
 No protocol-prohibited medication or treatment
 Change from baseline to Week 24 in SLEDAI-2K
score
 No new BILAG-2004 A or ≤ 2B to Week 24
 Change from baseline to Week 24 in PGA (VAS)
score
Pharmacokinetics Objectives and Endpoints:
To evaluate the pharmacokinetic parameters of BIIB059.
The endpoints that relate to this objective are BIIB059 clearance,
volume of distribution and absorption rate.
Safety and Tolerability Objectives and Endpoints
To evaluate the safety and tolerability of BIIB059.
The endpoints that relate to this objective are the:
 Nature, severity, relationship to study treatment and
incidence of adverse events (AEs) and serious
adverse events (SAEs)
 Change from baseline in standard laboratory
parameters, vital signs and electrocardiogram (ECG)
results
 Immunogenicity (antibodies to BIIB059)
 Absolute and percent change from baseline over time
in immunoglobulin levels and vaccine titers

Inclusion Criteria (Parts A and B)
To be eligible to participate in this study, candidates must meet the following eligibility criteria
at Screening or at the time point specified in the individual eligibility criterion listed:
1. Ability of the subject to understand the purpose and risks of the study and provide signed
and dated informed consent and authorization to use confidential health information in
accordance with national and local subject privacy regulations.
2. Age 18 to 75 years old, inclusive, at the time of informed consent.
3. All women of childbearing potential and all men must practice effective contraception
during the study and for 4 months after their last dose of study treatment. For further
details of contraceptive requirements for this study, please refer to Section 15.5.
4. CLASI-A ≥ 8 at Screening and Randomization.

Inclusion Criteria (Part A Specific)
1. Diagnosis of SLE fulfilling at least 4 out of 11 1997 revised ACR classification criteria
for SLE, with a diagnosis made ≥ 24 weeks prior to signing the informed consent form
(ICF).
2. Positive antinuclear antibody test at Screening (central laboratory titer >1:80) and/or
elevated anti-double-stranded DNA (≥ 30IU/ml).
3. SLEDAI-2K ≥ 4 at Screening and Randomization (excluding fever).

Exclusion Criteria (Parts A and B)
Candidates will be excluded from study entry if any of the following exclusion criteria exist at
Screening, or at the time point specified in the individual criterion listed:
1. Current enrollment or a plan to enroll in any interventional clinical study in which an
investigational treatment or approved therapy for investigational use is administered
within 5 half-lives of the agent, prior to Screening. (Participation in observational
registries is allowed).
2. Previous registration in this study or previous studies with BIIB059.
3. Inability to comply with study requirements.
4. Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the
subject unsuitable for enrollment.
Medical Condition
5. History or positive test result at Screening for human immunodeficiency virus.
6. Positive test result at Screening for hepatitis C virus antibody.
7. Positive test result at Screening for hepatitis B virus (defined as positive for both hepatitis
B surface antigen AND hepatitis B core antibody).
8. Active lupus nephritis or moderate-to-severe or chronic kidney disease (urine protein to
creatinine ratio >2.0 or estimated glomerular filtration rate < 30 mL/min/1.73m2
calculated using the abbreviated Modification of Diet in Renal Disease equation.
9. Subjects with a history of suicide attempt or suicidal ideation within 1 year prior to
Screening.
10. Active neuropsychiatric SLE including but not limited to the following: seizure, new or
worsening impaired level of consciousness, psychosis, delirium or confusional state,
aseptic meningitis, ascending or transverse myelitis, chorea, cerebellar ataxia,
mononeuritis multiplex, or demyelinating syndromes.
11. Any active skin conditions other than CLE that may interfere with the study (e.g.,
psoriasis, non-LE skin lupus, drug-induced lupus).
12. Systemic comorbidities requiring systemic corticosteroid therapy (e.g. asthma or
inflammatory bowel disease); systemic therapy is defined as treatment given orally,
rectally, or by any injectable route of administration. (Comorbidities that require
corticosteroid use administered by other routes, including inhaled, ophthalmic, otic, and
intranasal, are allowed).
13. History of severe herpes infection such as herpes encephalitis, ophthalmic herpes and
disseminated herpes.
14. History of chronic, recurrent, or recent serious infection (e.g., pneumonia, septicemia) as
determined by the Investigator and requiring anti-infective treatment within 3 months
prior to Screening.
15. Signs of herpes or varicella zoster viral infection (specifically chicken pox, shingles, or
herpes zoster) within 3 months prior to Screening.
16. Active clinically significant viral, bacterial, or fungal infection, or any major episode of
infection requiring hospitalization or treatment with parenteral anti-infectives within 4
weeks of or during Screening, or completion of oral anti-infectives within 2 weeks before
or during Screening. Vaginal candidiasis, onychomycosis, and genital or oral herpes
simplex virus considered by the Investigator to be sufficiently controlled will not be
exclusionary.
17. History of or current diagnosis of active tuberculosis (TB), or untreated latent TB
infection (LTBI), determined by a TB skin test with purified protein derivative as
evidenced by induration ≥ 5 mm or a positive Quantiferon, positive or borderline
T-SPOT (Elispot) test performed locally, either at Screening or documented with results
within 3 months of the Screening Visit. Subjects who have previously completed
appropriate and documented LTBI treatment or who are undergoing current treatment for
LTBI will not be required to be tested. If the subject is undergoing current treatment for
LTBI, they must have received at least 4 continuous weeks of an appropriate LTBI
treatment prior to Screening without evidence of re-exposure. If receiving LTBI
treatment at Screening, the subject will be expected to complete an appropriate LTBI
treatment regimen to remain in the trial.
a. Subject with current household contacts with active TB will also be excluded unless
the subject is being treated and there is evidence that household contacts are being
treated
b. Indeterminate Quantiferon or T-SPOT tests may be repeated once, and will be
considered positive if retest results are positive or indeterminate
18. Presence of uncontrolled or New York Heart Association class III or IV congestive heart
failure.
19. Known hypersensitivity to BIIB059 or any of the components of the formulated BIIB059
or matching placebo.
20. History of severe allergic or anaphylactic reactions.
21. History of, or ongoing, malignant disease, including solid tumors and hematologic
malignancies with the exception of basal cell carcinomas and squamous cell carcinomas
that have been completely excised and considered cured at least 12 months prior to
Screening and carcinoma in situ of the cervix > 5 years prior to Screening.
22. History of any clinically significant cardiac, endocrinologic, hematologic, hepatic,
immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric and
renal, or other major disease, as determined by the Investigator.
23. History of substance abuse within 6 months prior to Screening.
24. Female subjects who are pregnant or currently breastfeeding, or are planning to become
pregnant during the study and for 4 months after the last dose of study treatment.
Concomitant and Previous Therapies
25. Use of high potency topical and/or intralesional corticosteroid within 1 month prior to
Screening and during the study.
26. Use of thalidomide or lenalidomide within 2 months of Screening and during the study.
27. Use of cyclosporine, tacrolimus, picrolimus, sirolimus, imiquimod, IV immunoglobulin,
IV and oral cyclophosphamide and plasmapheresis within 3 months of Screening and
during the study.
28. Use of rituximab, atacicept, ocrelizumab, or other B cell-directed biologic therapies
within 6 months before Screening and during the study. Subjects with prior
B cell-directed therapies within 12 months of Screening will be excluded if total CD19
B cell level is < 25 cells/µL as measured locally at Screening.
29. Use of abatacept, belimumab, tocilizumab or tumor necrosis factor (TNF) inhibitors
within 3 months or 5 half-lives, whichever is longer, before Screening and during the
study.
30. Treatment with any investigational agent that blocks IFNα within 6 months of Screening.
31. Use of immunosuppressive or disease-modifying treatments for SLE that were initiated
less than 3 months prior to Screening, have not been at a stable dose for at least 1 month
prior to Screening, or have been taken at doses above the prescribed maximum listed
here: antimalarials (hydroxychloroquine 6.5 mg/kg/day maximum, quinacrine 5
mg/kg/day maximum, chloroquine 3 mg/kg/day), dapsone 150 mg/day, methotrexate
20 mg/week, azathioprine 200 mg/day, 6-mercaptopurine 1.5 mg/kg/day, and
mycophenolate mofetil (MMF) 2 g/day or mycophenolate sodium (MPS) 1440 mg/day.
32. Initiation of disease-modifying antirheumatic agents or immunosuppressive treatments
with the exception of those listed in exclusion criteria 31, within 3 months of Screening
and during the study.
33. Immunizations with live or live-attenuated vaccines within 1 month before Screening and
throughout the study and for 4 months after the last dose of study treatment.
34. Allergy shots or completion of desensitization therapy within 1 month prior to Screening.
Laboratory abnormalities
35. Aspartate aminotransferase or alanine aminotransferase > 2.0 times the upper limit of
normal.
36. Hemoglobin < 5.5 mmol/L [9 g/dL], neutrophils < 1.5 x 103
/L, platelets < 75 x 109
/L.
37. Any abnormal laboratory test result at Screening that is considered clinical significant, as
determined by the Investigator and would preclude the subject from participating in the
study. A nonclinically significant out-of-range laboratory value would not be considered
exclusionary.