The Study of Comparing the Efficacy and Safety of Human Umbilical Cord MSCs and Low-dose IL-2 in the Treatment of LN

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of human umbilical cord mesenchymal stem cells and low-dose IL-2 in the treatment of LN

Detailed Description
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Allogeneic MSC transplantation has shown significant efficacy and good safety in the treatment of refractory autoimmune diseases such as lupus nephritis (LN), and has a broad application prospect. One of its mechanisms is that MSCs up-regulates the production of IL-2 and promotes the production of Treg cells. The breakthrough in this technology has brought new hope for patients with autoimmune diseases. Some small sample studies at home and abroad have shown that low-dose IL-2 can be used to treat LN. Recently, the research team found that a single dose of IL-2 showed a longer effect than repeated low-dose MSCs. However, there is still a lack of prospective randomized studies to confirm that the efficacy of allogeneic MSC is better than that of low-dose IL-2. Therefore, carrying out this prospective randomized study will make a real breakthrough in the clinical application of MSC in SLE, and open up a new field for the treatment of SLE for the benefit of mankind.

Official Title
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A Prospective, Single-center Study of Comparing the Efficacy and Safety of Human Umbilical Cord Mesenchymal Stem Cells and Low-dose IL-2 in the Treatment of Lupus Nephritis

Conditions
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Systemic Lupus Erythematosus, Lupus Nephritis

Intervention / Treatment
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* Biological: Human umbilical cord mesenchymal stem cells
* Drug: Interleukin-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Only patients with active lupus nephritis who meet all of the following criteria are eligible for inclusion in this study: Before random assignment, records show that it meets at least 4 of the 11 SLE classification criteria recommended by ACR in 1997. Age: age > 18 years old, ≤ 65 years old when obtaining informed consent SLEDAI-2K score ≥ 6 Urinary total protein / creatinine ratio > 1.0 or 24-hour urinary protein > 1.0g, with or without microscopic hematuria If they are fertile, they must agree to use effective contraception during the trial. In the case of women of childbearing age, urinary pregnancy and serum pregnancy tests should be negative. Voluntarily sign informed consent and comply with the requirements of the research programme Exclusion Criteria: Patients who met any of the following criteria could not be enrolled in this study: Patients who had received rituximab or any other B cell depletion therapy within 24 weeks before screening; patients who received unstable doses of mycophenolate mofetil, cyclophosphamide or other immunosuppressants (including Cyclosporine, Tacrolimus, Tripterygium wilfordii, Leflunomide, Azathioprine, Iguratimod) within the first 12 weeks of screening. Received biological agents or small molecule targeted drugs for immune diseases within 4 weeks before screening, such as Etanercept, Infliximab, Adalimumab Solution, Golimumab, Belimumab, Tocilizumab or JAK inhibitors; Plasmapheresis or immunosorbent therapy within 12 weeks before screening. Accompanied by severe and uncontrolled cardiovascular diseases, nervous system diseases, lung diseases, liver diseases, endocrine and gastrointestinal diseases. Current or recent (within 4 weeks before random allocation) a history of severe active or recurrent bacterial, viral, fungal, parasitic or other infections (including, but not limited to, tuberculosis and atypical mycobacterial diseases, hepatitis B and C, HIV infection, herpes zoster, but excluding onychomycosis). Or any infected person who needs hospitalization and intravenous antibiotic treatment within 4 weeks before screening or any infected person who needs treatment within 2 weeks before screening. Any major surgery has been performed within 12 weeks before screening, or major surgery is required during the study period, which the researchers believe will pose an unacceptable risk to the patient; Live vaccine will be given within 12 weeks before random allocation, or live vaccine is expected to be needed / received during the study (except for herpes zoster vaccination). Patients with a history of malignant tumors, including solid tumors and hematological malignancies (except for excised or cured basal cell carcinoma of the skin); Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The test will be divided into two groups. One group of subjects will receive intravenous injection of human umbilical cord mesenchymal stem cells (2 × 106 cells/kg body weight, suspended in 30ml of normal saline); the other group will receive IL-2 (1 × 106 IU) every other day. Subcutaneous injection for 2 weeks (a total of 7 injections), with an interval of 2 weeks, such that 4 weeks is a cycle, and three consecutive cycles of treatment for a total of 12 weeks.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSCs group<br>In this group, patients will receive intravenous injection of human umbilical cord mesenchymal stem cells (2 × 10^6 cells / kg body weight, suspended in 30ml saline) | Biological: Human umbilical cord mesenchymal stem cells<br>* Human umbilical cord mesenchymal stem cells (1 × 10 ^6 cells / kg body weight, suspended in 30ml saline), intravenous drip once.<br>|
| Experimental: IL-2 group<br>In this group, patients will receive subcutaneous injection of IL-2 (1×10^6IU) every other day for 2 weeks (7 times), with an interval of 2 weeks. | Drug: Interleukin-2<br>* IL-2 (1×10^6IU) will be injected subcutaneously every other day for 2 weeks (7 times), with an interval of 2 weeks. 4 weeks is a cycle, and three cycles were continuously treated for 12 weeks.<br>* Other names: Recombinant Human Interleukin-2(1) for Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rates in both groups （CR and RR） | Complete response (CR): serum creatinine ≤ 1.2 mg/dl or ≤125% of baseline, and ratio of protein in morning urine to creatinine <0.5 or 24-hour urine protein quantification < 0.5 g, and prednisone reduced to ≤10 mg/day (or equivalent). Partial response (PR): if serum creatinine and ratio of protein in morning urine to creatinine (or 24-hour urine protein quantification) were abnormal before treatment, both improved by >30% after treatment, and there were no other indicators of deterioration; If only the ratio of protein in morning urine to creatinine (or 24-hour urine protein quantification) is abnormal before treatment, the improvement is >50% after treatment. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time for both groups of subjects to achieve PR and CR | Complete response (CR): serum creatinine ≤ 1.2 mg/dl or ≤125% of baseline, and ratio of protein in morning urine to creatinine <0.5 or 24-hour urine protein quantification < 0.5 g, and prednisone reduced to ≤10 mg/day (or equivalent). Partial response (PR): if serum creatinine and ratio of protein in morning urine to creatinine (or 24-hour urine protein quantification) were abnormal before treatment, both improved by >30% after treatment, and there were no other indicators of deterioration; If only the ratio of protein in morning urine to creatinine (or 24-hour urine protein quantification) is abnormal before treatment, the improvement is >50% after treatment. | 24 Weeks | 
| SRI response status | SRI response status at Week 24 Clinical efficacy will be measured using the SLE Responder Index (SRI), a composite endpoint that incorporates SLEDAI-2K, BILAG 2004, and a visual analog scale (VAS) of physician-rated disease activity to determine patient improvement. | 24 Weeks | 
| SLEDAI-2K score and change from baseline | To describe the effect of treatment with MSCs or IL-2 using patient reported outcomes | Baseline, Week 4, 8, 16, 20 and 24 | 
| BILAG-2004 score and change from baseline | To describe the effect of treatment with MSCs or IL-2 using patient reported outcomes | Baseline, Week 4, 8, 16, 20 and 24 | 
| Hormone dosage and change from baseline | To describe the effect of treatment with MSCs or IL-2 using dose of hormones in patients | Baseline, Week 4, 8, 16, 20 and 24 | 
| Patient incidence of Treatment-Emergent Adverse Events | To characterize the safety of MSCs and IL-2 | 24 Weeks | 
| Patient incidence of Serious adverse events | To characterize the safety of MSCs and IL-2 | 24 Weeks | 
| Number of patients with significant changes in laboratory values | To characterize the safety of MSCs and IL-2 | 24 Weeks | 
| Number of patients with significant changes in vital signs | To characterize the safety of MSCs and IL-2 | 24 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stem cells, interleukin-2