Clinical Drug Experience Knowledgebase

Criteria

Key Inclusion Criteria:

PHASE 1b (fully enrolled):

Male or female patients aged 18 to 75 (inclusive)
Body Mass Index (BMI) of 18-40 kg/m2
Fulfills the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE

Have at least one of the following at screening per central lab:

Positive antinuclear antibody (ANA) test (1:80 or higher); or
Anti-double stranded deoxyribonucleic acid (dsDNA) antibodies elevated to above normal (i.e. positive results); or
Anti-Smith antibody elevated to above normal (i.e., positive results)
Active SLE as indicated by a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score ≥4 at screening

Must have received 1 or more of the following therapies for SLE, each administered at or higher than the minimum dose indicated for at least 12 weeks (unless discontinued or dose adjusted for documented drug-related toxicity or size/weight):

Hydroxychloroquine 200 mg orally daily in combination with prednisone 10 mg daily or equivalent
MMF orally 1 g/day or MPA orally 720 mg/day
Methotrexate orally or SC 15 mg/wk., or leflunomide orally 10 mg/day
Azathioprine (AZA) 100 mg/day or 6-mercaptopurine 50 mg/day (50 or 25 mg/day, respectively, permitted in cases of documented thiopurine methyltransferase [TPMT] polymorphism) orally
Cyclosporine or tacrolimus at doses documented to maintain at least 100 or 5 ng/mL during the required duration, respectively
Cyclophosphamide 500 mg intravenously (IV) every 2 weeks or 500 mg/m2 IV once monthly
Belimumab 10 mg/kg IV every 2 weeks for 3 doses, followed by 10 mg/kg every 4 weeks; or 200 mg SC weekly
Rituximab 1 g IV (may be given as 500 mg twice)

Acceptable screening laboratory values of concern, including:

Adequate hematologic criteria
Adequate hepatic function
eGFR ≥40 mL/min/1.73 m2
IgG ≥500 mg/dL
Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening and a negative urine pregnancy test prior to the first dose
Male patients must use an effective contraception method (e.g. condom with spermicide) from signing the ICF until their completion of the study

PHASE 2 (enrolling):

Male or female patients aged 18 to 75 years (inclusive)
BMI of ≥18kg/m2
Fulfills the 2012 SLICC classification criteria for SLE

At least one of the following at Screening per central lab:

Positive ANA test; or
Anti-dsDNA antibodies elevated to above normal; or
Anti-Smith antibody at Screening elevated to above normal
Active lupus nephritis with UPCR ≥1.0 measured in 24-hour urine collection
Currently receiving one or more immunosuppressive agents
Renal biopsy with a histologic diagnosis of LN (ISN/RPS) Classes III, IV-S or IV-G, (A) or (A/C) +/- Class V

Acceptable screening laboratory values of concern, including:

Adequate hematologic criteria
Adequate hepatic function
eGFR ≥30mL/min/1.73 m2
IgG ≥500 mg/dL
Female patients of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline
Male patients with a partner of childbearing potential must be either congenitally sterile or surgically sterile (by vasectomy) or willing to use a condom in addition to having their female partner use another form of contraception

Key Exclusion Criteria:

PHASE 1b (fully enrolled):

Active central nervous system involvement by autoimmune disease requiring specific therapeutic intervention within 60 days prior to first day of study treatment.
Presence of another rheumatic (overlap) disease that may confound clinical assessments in the study.
History of antiphospholipid syndrome with thromboembolic event within 12 months of screening or not on an adequate anticoagulation regimen. However, presence of antiphospholipid antibodies alone (without a history of thromboembolic event) is not exclusionary.

Receipt of any of the following treatments within the following timeframes before Screening

Systemic corticosteroids ≥ 100 mg prednisone or equivalent: 4 weeks
Intra-articular therapies, such as corticosteroids or hyaluronic acid preparations: 4 weeks
Intravenous Immunoglobulin (IVIg): 4 weeks
Other non-biologic immunosuppressive agents, such as cyclosporine, tacrolimus: 4 weeks
Cyclophosphamide: 12 weeks
Cytokine antagonists, including but not limited to interleukin (IL)-1, IL-6, IL-17, IL-12/23, IL-23, interferon (IFN), integrin, and tumor necrosis factor (TNF)-α antagonists: 12 weeks
B-cell-depleting therapies (e.g., rituximab): 24 weeks with levels of circulating cluster of differentiation 19+ (CD19+) B cells within normal limits or 48 weeks if CD19+ count is not available
Belimumab, abatacept, or atacicept: 12 weeks
Other biologics or investigational drugs: 8 weeks or 5 half-lives, whichever is longer
Transfusion with blood, packed red blood cells, platelets or treatment with plasmapheresis or plasma exchange: 6 weeks

Patient has had recent serious or ongoing infection, or risk for serious infection

Acute or chronic infections:

Requiring systemic antibiotic, antifungal, or antiviral (antimicrobial) therapy within 14 days of Week 1, Day 1
Requiring hospitalization or a course of IV antimicrobial therapy within 24 weeks prior to screening
History of severe and/or disseminated viral infections, and/or opportunistic infections
Known seropositivity for or active infection by human immunodeficiency virus (HIV)
Active, chronic, or resolved hepatitis B or hepatitis C infection
History of progressive multifocal leukoencephalopathy
Active or latent tuberculosis (TB), as suggested by chest x-ray within the 12 weeks prior to screening and/or QuantiFERON®-TB Gold at Screening
Receipt of a live-attenuated vaccine within 12 weeks of first day of study treatment (Week 1, Day 1)
Primary immunodeficiency (unless otherwise considered, in the opinion of the investigator and medical monitor, to confer a clinically insignificant infection risk, such as deficiency in immunoglobulin A (IgA), C1q, C2, or C4 without a history of recurrent infections [3 or more infections in 1 year requiring antimicrobial therapy])
History of any concurrent illness that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF
Clinical evidence of significant unstable or uncontrolled acute or chronic diseases
History of cancer, except for in situ cancer that has been completely excised or has been curatively treated cancer with no sign of disease for > 5 years
Major surgery within 4 weeks before signing the ICF or major surgery planned during the study period

PHASE 2 (enrolling):

Any of the following: dialysis within 12 months prior to screening, rapidly progressive glomerulonephritis (RPGN), chronic kidney disease not due to lupus nephritis, >50% sclerosed glomeruli on most recent renal biopsy
Presence of another rheumatic (overlap) disease that may confound clinical assessments in the study. Secondary sicca or Sjogren's syndrome and antiphospholipid antibody syndrome are allowed
History of antiphospholipid syndrome with history of thromboembolic event within 12 months of screening
Active central nervous system involvement by autoimmune disease requiring specific therapeutic intervention within 60 days prior to first day of study treatment.
Active or chronic infection

Patient has or had any of the following:

Progressive multifocal leukoencephalopathy
Active or untreated latent TB, per QuantiFERON-TB Gold at Screening
Receipt of a live-attenuated vaccine within 12 weeks of Baseline (Week 1, Day 1)
Primary immunodeficiency (unless otherwise considered, in the opinion of the investigator and medical monitor, to confer a clinically insignificant infection risk, such as deficiency in IgA, C1q, C2, or C4 without a history of recurrent infections [3 or more infections in 1 year requiring antimicrobial therapy])
Primary hematopoietic cell or solid organ transplant
Any active or suspected malignancy or history of documented malignancy within the last 5 years before Screening