The primary purpose of this Phase 1 study is to evaluate the safety, tolerability, and
effect of 3 different doses of Treg therapy in adults with skin (cutaneous) involvement of
their lupus. Targeting cutaneous disease offers the ability to control background therapy,
readily detect clinical effects, and perform research analyses not only in blood but also
skin. Safety, disease activity, and mechanism of Tregs will be evaluated. The intent is to
support dose selection for a future larger efficacy trial in lupus.
The investigational therapy in this trial, regulatory T cells (Tregs), is evaluating an
alternative to traditional immunosuppressive therapies for the treatment of systemic lupus
erythematosus (SLE, lupus). Too frequently, aggressive therapies are inadequate in the
control of the disease and have potent side effects and complications. The collection and
expansion of one's own T cells harnesses a naturally occurring regulatory mechanism to
restore self-tolerance in people with lupus. Tregs are a specialized subset of T cells that
function to control the immune response. Studies have shown that in active lupus, the
numbers and function of Treg cells are significantly decreased, which contributes to an
overactive immune system and an increase in disease activity. The hope is that these
naturally occurring Treg cells can be used for the treatment of autoimmune diseases,
- Ability to provide informed consent.
- Diagnosis of SLE by American College of Rheumatology (ACR) criteria or biopsy proven
primary cutaneous lupus.
- Presence of ≥ 2 active cutaneous lupus lesions based on (1) visual morphology and (2)
at least a grade 2 erythema on CLASI activity score. Histopathologic confirmation is
required unless the active lesions are of the same morphology to previously
histologically proven cutaneous lupus lesions.
- The cutaneous lupus lesions must include any of the following subtypes:
- Acute cutaneous lupus including maculopapular lupus rash and photosensitive
- Subacute cutaneous lupus,
- Chronic cutaneous lupus including discoid lupus and hypertrophic (verrucous)
- Lupus timidus
- Positive test for Epstein-Barr virus (EBV) antibody.
- Adequate venous access to support draw of 400 mL whole blood and infusion of
- New onset of cutaneous lupus which has not been treated with broad spectrum sunscreen
(UVA and UVB) in combination with either antimalarials or another systemic medication
for at least 3 months.
- Prednisone dose > 15mg/day within the 30 days prior to screening.
- Addition of a new medication, or change in the dose of any background medication,
used to treat any aspect of SLE. Specifically:
- addition or change in systemic glucocorticoids, antimalarials, methotrexate,
mycophenolate mofetil, mycophenolic acid, azathioprine, cyclosporine,
tacrolimus, thalidomide, lenalidomide, dapsone, acitretin, or isotretinoin
within 90 days prior to screening
- treatment with cyclophosphamide within 90 days prior to screening.
- Doses of background medications at Screening visit:
- hydroxychloroquine > 400 mg/day,
- chloroquine > 250 mg/day,
- quinacrine >100 mg/day,
- methotrexate > 25 mg/week,
- mycophenolate mofetil (MMF)> 3000 mg/day,
- mycophenolic acid > 720 mg/day BID,
- azathioprine > 200 mg/day,
- cyclosporine > 5 mg/day divided BID,
- tacrolimus > 6 mg/day
- thalidomide > 300 mg/day,
- lenalidomide > 10 mg/day,
- dapsone > 250 mg/day,
- acitretin > 50 mg/d (or > 1 mg/kg/day),
- isotretinoin > 120 mg/d (or > 2 mg/kg/day).
- Intravenous immunoglobulin (IVIG), plasmapheresis, or leukopheresis within the 90
days prior to screening.
- Use of rituximab within the 12 months prior to screening.
- Change in dosing frequency, concentration, or applied surface area of topical
steroids, tacrolimus, and/or pimecrolimus within 4 weeks prior to screening.
- Active severe central nervous system lupus.
- SELENA-SLEDAI's seizure, psychosis, organic brain syndrome, visual
disturbance,cranial nerve disorder, lupus headache, cerebrovascular accident (CVA),
vasculitis,arthritis, myositis, mucosal ulcers, pleurisy, pericarditis, and fever
scores > 8 total.
- Active lupus nephritis (spot protein / creatinine ratio > 1.0 mg/mg).
- End stage renal disease (estimated glomerular filtration rate [eGFR] < 20
ml/min/1.73m^2 using the CKD-EPI equation ).
- Drug induced lupus.
- Hemoglobin < 10 g/dL.
- White blood cell (WBC) count < 2,500/ mm^3 (equivalent to < 2.5 x109/L).
- Lymphocyte count < 625/mm^3 (equivalent to < 0.625 x109/L).
- Absolute neutrophil count < 1,500/mm3 (equivalent to < 1.5 x109/L).
- Platelets < 75,000/mm^3 (equivalent to < 75 x 109/L).
- Liver function test (aspartate aminotransferase [AST], alanine aminotransferase
[ALT], or alkaline phosphatase [ALK]) results that are ≥ 2 times the upper limit of
- Direct bilirubin > ULN.
- Active bacterial, viral, fungal, or opportunistic infections requiring systemic
- Presence of positive purified protein derivative tuberculin skin test (PPD, > 5mm
induration [regardless of Bacille Calmette Guerin (BCG) vaccine administration]) or
positive or indeterminate QuantiFERON(R)-TB Gold In-Tube Test (QFT-G_IT) at
- Evidence of infection with human immunodeficiency virus (HIV), hepatitis B (as
assessed by HBsAg and anti-HBc) or hepatitis C.
- Detectable circulating EBV or cytomegalovirus (CMV) genomes or active infection.
- Chronic infection that is currently being treated with suppressive anti-infective
therapy, including but not limited to tuberculosis, pneumocystis, CMV, herpes zoster,
and atypical mycobacteria.
- Herpes simplex virus infection requiring chronic, suppressive therapy with an
- Receipt of a live-attenuated vaccine within 12 months prior to screening.
- Concomitant malignancies or a history of malignancy, with the exception of adequately
treated basal and squamous cell carcinoma of the skin, or carcinoma in situ of the
- Unwilling or unable to use reliable method(s) of contraception from four weeks prior
to Day 0 throughout three months after Treg dosing (males) or for two years after
Treg dosing (females). Note: investigators of female participants of childbearing
potential on concurrent MMF, and those participants themselves, whether or not they
plan to become pregnant, are strongly encouraged to participate in Mycophenolate Risk
Evaluation and Mitigation Strategy (REMS).
- Use of an experimental therapeutic agent within the calendar year prior to screening.
- Use of biologic medications other than rituximab within the 90 days or 5
half-lives,whichever is greater, prior to screening.
- Concomitant medical condition that places the subject at risk by participating in
this study, including but not limited to:
- another severe, systemic autoimmune disease or condition (besides lupus)
requiring systemic immunosuppressive therapy (e.g., rheumatoid arthritis,
systemic sclerosis, primary Sjogren's syndrome, primary vasculitis, psoriasis,
multiple sclerosis, ankylosing spondylitis, and inflammatory bowel disease), or
- severe, progressive, or poorly controlled renal, hepatic, hematological,
gastrointestinal, pulmonary, cardiac, or neurological disease, either related or
unrelated to SLE, or
- history of significant infection or recurrent infection that, in the
investigator's opinion, places the subject at risk by participating in this
- any other concomitant medical condition that, in the investigator's opinion,
places the subject at risk by participating in this study.
- Comorbidities requiring glucocorticoid therapy, including those which have required
three or more courses of systemic glucocorticoids within the previous 12 months.
- Current or history within the past year of substance abuse.
- Inability to comply with study and follow-up procedures.