The goal of this clinical trial is to evaluate the safety and effectiveness of UC-MSCs in adults with systemic lupus erythematosus (SLE).
The main questions this study aims to answer are:
1. Can UC-MSCs improve kidney function and reduce SLE disease activity? 2. Are UC-MSCs safe and well-tolerated in this patient population?
Participants in this study will:
* Receive UC-MSCs in a single dose in addition to standard of care treatment. * Provide blood and urine samples for laboratory assessments, including biomarkers and immune profiling (e.g., cytokines, complement proteins, and autoantibodies). * Attend regular clinic visits for physical exams, disease activity scoring, and imaging tests to monitor kidney health. * Complete assessments for safety, such as monitoring for adverse events and changes in laboratory values.
This study aims to provide new insights into treatment options for SLE and lupus nephritis, addressing an unmet medical need in this population.
Age 18-75 years at the time of screening
Diagnosis of systemic lupus erythematosus (SLE), meeting at least 4 of the 11 criteria included in the American College of Rheumatology (ACR) Classification Criteria and/or 4 of the 17 criteria (with at least one of those being clinical and at least one being immunologic) included in the Systemic Lupus International Collaborating Clinics (SLICC) Criteria, at the screening visit.
Must have a positive ANA (≥1:160 titer) or positive anti-dsDNA antibody test within 6 months of the screening visit
An eGFR of ≥ 30 mL/min/1.73 m2 in the screening period
History of any non-systemic lupus erythematosus (non-SLE) disease that required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the 12 weeks preceding the screening visit.
History of dialysis within 12 months prior to the screening visit or expected need for renal replacement therapy (dialysis or renal transplant) within a six-month period after enrollment.
Use of prednisone >0.5 mg/kg/day (or equivalent corticosteroid) in the 4 weeks prior to the screening visit.
Any change or addition to a non-biologic immunosuppressant and/ or antimalarial regimen (not including corticosteroids) ≤ 12 weeks prior to the Screening visit.
Single group
Physical examination
Diagnostic testThe physical examination will be performed at the Screening visit and at each subsequent study and safety in clinic follow-up visit. The exam will include: measurement of vital signs (heart rate, peripheral arterial blood pressure, respiratory rate, and temperature), weight, height (at Screening visit only), cardiovascular and respiratory systems, abdominal examination, skin evaluation, mouth and eye evaluation, and neurological assessment. Abnormal findings will be recorded in the CRF.
Electrocardiogram
Diagnostic testA twelve-lead electrocardiogram (ECG), including corrected QT interval (QTc interval), will be performed in all participants at the Screening visit.
SF-36 questionnaire
Other interventionPatients will fill out the SF 36 survey, assessing physical and mental health outcomes prior to dosing and/or any other clinical assessments, on visits 1 (baseline), visit 5 (day 14), visit 6 (day 28), visit 11 (day 168) and early termination visit.
Clinical laboratory evaluations - Serology
Diagnostic testSerologic testing for HIV, HBV, HCV, TB, and CMV will be performed; HBV and HCV PCR will be done only if serology is positive. Autoimmune tests (ANA, anti-ENA, total IgG, anti-nucleosome) will be done at Day 0 and end of study; ANA only at Screening if no positive ANA or anti-dsDNA in prior 6 months. Inflammatory markers (hs-CRP, ESR) will be tested at Day 0 and end of study. CBC with differential, biochemistry, anti-dsDNA, and complement C3/C4 will be assessed at each scheduled visit.
Clinical laboratory evaluations - Biochemistry
Diagnostic testThe panel will include analysis of albumin, blood urea nitrogen (BUN), creatinine, glucose, uric acid, calcium, phosphorus, potassium, sodium, lactate dehydrogenase (LDH), total protein, magnesium, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and hs-CRP. For biochemistry, 3 mL blood will be collected at each study visit. Results relating to inclusion criteria must be confirmed within 7 days prior to Day 1.
Clinical laboratory evaluations - Hematology
Diagnostic testThe complete blood count (CBC) will include: hemoglobin, hematocrit, white blood cells (WBCs) with complete manual or automated differential (total neutrophils, lymphocytes, monocytes, eosinophils, basophils; absolute or percentage will be acceptable), red blood cells (RBCs), platelet count. For CBC, 1mL blood will be collected at each study visit.
Pregnancy Test
Diagnostic testA serum b-hCG pregnancy test will be performed for women of child-bearing potential at the Screening visit;urine pregnancy tests will be performed for women of child-bearing potential at each study visit noted above, including on Day 0 prior to study treatment. Pregnancy tests are not required for women unable to become pregnant for one of the following reasons: Menopause confirmed by healthcare provider, verbally reported by a participant that she has had her uterus or both ovaries or both fallopian tubes removed.
Urinalysis
Diagnostic testGeneral urinalysis will include analysis of pH, specific gravity, protein, glucose, ketones, bilirubin, urobilinogen, leukocytes, erythrocytes. In addition samples will be assessed for presence of urinary casts. Spot urine protein/creatinine measure will be done at each visit. If no casts are observed at Screening, then machine assessment of further urinary samples is allowed. For urinalysis, 10mL urine will be collected at each study visit.
SLE activity evaluation
Diagnostic testSLE status will be assessed using the Safety of Estrogens in Lupus Erythematosus National Assessment- SLE Disease Activity Index (SLEDAI 2K scale).SLE activity will also be assessed using British Isles Lupus Assessment Group (BILAG), physician global and participant global assessment allowing use of the Systemic Lupus Responder Index (SRI 4) and the BILAG-based Composite Lupus Assessment (BICLA) instruments to assess clinical response.
SLE biomarker profiling
Diagnostic testSLE biomarkers will be profiled at the study visit (Day 1) and at every subsequent follow up visit. For this purpose, urine and 10 ml blood will be collected. Anti-ENA, Anti-dsDNA antibodies, total serum IgG levels, CBC, C3, C4, anti-nucleosome antibodies, erythrocyte sedimentation rate, CRP, protein/creatinine ratio in spot urine, 24-hour urine protein - Day 1 - Baseline and at end of study visit only; Mononuclear cell changes. This analysis includes lymphocyte subsets and innate immune cell subsets
Cytokines and chemokine profiling
Diagnostic testSamples will be analyzed for the following cytokines/chemokines: IFNγ, IL-6, IL-10, IL-18, TNFα, TGFβ1, CXCL10, CCL2, N-GAL, urine endothelin, KIM1. Serum and urine samples will be collected on Days 0, 28, 56, 140, 168, and early termination visit.
single dose of UC-MSCs
Biological/Vaccineparticipants will be treated on Baseline Day 1 with a UC-MSCs product administered subcutaneously. Participants will be observed for 2 to 3 hours after end of study treatment and then followed up for safety assessments over the subsequent 6-month period.
PROMIS instruments
Other interventionPROMIS Fatigue, PROMIS, Depression, PROMIS Pain prior to dosing and/or any other clinical assessments, on visits 1 (baseline, day 0), visit 5 (day 14), visit 6 (day 28), visit 11 (day 168) and early termination visit.
Incidence of Treatment-Emergent Adverse Events
Analysis for the primary endpoint will be descriptive in nature. safety and tolerability will be measured by the number of AEs and SAEs observed. Adverse event incidents will be summarized descriptively. The severity grade of each recorded AE, and their relationship to study treatment will be analyzed. The action taken and outcome will also be analyzed accordingly.
Change from baseline in the SLEDAI 2K following administration
Total score ranging from 0 to 105. Interpretation: Scores are categorized to indicate disease activity: 0: No activity 1-5: Mild activity 6-10: Moderate activity 11-19: High activity ≥20: Very high activity Improvement is defined as a decrease in score.
Change from baseline in PROMIS(Patient-Reported Outcomes Measurement Information System) score
Change from baseline in scores for quality of life, fatigue, pain, and depression as reported by the patient. Scores range from 0 to 100. Higher scores indicate worse symptoms.
Change from baseline in the BILAG-2004 Index score following administration
Organ involvement is categorized into grades: A: Severe active disease B: Moderate active disease C: Stable disease D: Resolved disease E: No involvement Improvement is defined as an increase in score.
Efficacy by SRI-4 Responder assessment at Day 168.
Change from baseline in SRI-4, defined as a ≥4-point reduction in SLEDAI, with no significant worsening in BILAG or PGA. A higher SRI-4 response rate reflects greater clinical improvement.
Change of pre-treatment versus post-treatment levels of Anti-ENA Antibodies
Improvement is defined as a decrease in anti-ENA antibody levels from pre-treatment to post-treatment measurements.
Change of pre-treatment versus post-treatment levels of Anti-dsDNA Antibodies
Improvement is defined as a reduction in antibody levels.
Change of pre-treatment versus post-treatment levels of Total Serum IgG Levels
Improvement is defined as a reduction in serum IgG levels.
Change of pre-treatment versus post-treatment results of CBC
Improvement is defined as any change in values compared to normal range.
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