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:
1.
Positive antinuclear antibody (ANA) test (1:80 or higher); or. 2. Anti-double stranded deoxyribonucleic acid (dsDNA) antibodies elevated to above
normal (i.e. positive results); or. 3. 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):
1.
Hydroxychloroquine 200 mg orally daily in combination with prednisone 10 mg daily
or equivalent. 2. MMF orally 1 g/day or MPA orally 720 mg/day. 3. Methotrexate orally or SC 15 mg/wk., or leflunomide orally 10 mg/day. 4. 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. 5. Cyclosporine or tacrolimus at doses documented to maintain at least 100 or 5
ng/mL during the required duration, respectively. 6. Cyclophosphamide 500 mg intravenously (IV) every 2 weeks or 500 mg/m2 IV once
monthly. 7. Belimumab 10 mg/kg IV every 2 weeks for 3 doses, followed by 10 mg/kg every 4
weeks; or 200 mg SC weekly. 8. Rituximab 1 g IV (may be given as 500 mg twice)
- - Acceptable screening laboratory values of concern, including:
1.
Adequate hematologic criteria. 2. Adequate hepatic function. 3. eGFR ≥40 mL/min/1.73 m2. 4. 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:
1.
Positive ANA test; or. 2. Anti-dsDNA antibodies elevated to above normal; or. 3. 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:
1.
Adequate hematologic criteria. 2. Adequate hepatic function. 3. eGFR ≥30mL/min/1.73 m2. 4. 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.
1. Systemic corticosteroids ≥ 100 mg prednisone or equivalent: 4 weeks. 2. Intra-articular therapies, such as corticosteroids or hyaluronic acid
preparations: 4 weeks. 3. Intravenous Immunoglobulin (IVIg): 4 weeks. 4. Other non-biologic immunosuppressive agents, such as cyclosporine, tacrolimus: 4
weeks. 5. Cyclophosphamide: 12 weeks. 6. 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. 7. 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. 8. Belimumab, abatacept, or atacicept: 12 weeks. 9. Other biologics or investigational drugs: 8 weeks or 5 half-lives, whichever is
longer. 10. 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.
1. 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.
2. History of severe and/or disseminated viral infections, and/or opportunistic
infections. 3. Known seropositivity for or active infection by human immunodeficiency virus
(HIV)
4. Active, chronic, or resolved hepatitis B or hepatitis C infection. 5. History of progressive multifocal leukoencephalopathy. 6. 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. 7. Receipt of a live-attenuated vaccine within 12 weeks of first day of study
treatment (Week 1, Day 1)
8. 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:
1.
Progressive multifocal leukoencephalopathy. 2. Active or untreated latent TB, per QuantiFERON-TB Gold at Screening. 3. Receipt of a live-attenuated vaccine within 12 weeks of Baseline (Week 1, Day 1)
4. 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])
5. Primary hematopoietic cell or solid organ transplant. - Any active or suspected malignancy or history of documented malignancy within the last
5 years before Screening
