Clinical trial NCT05631717: The Study of Comparing the Efficacy and Safety of Human Umbilical Cord MSCs and Low-dose IL-2 in the Treatment of LN
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Lupus Nephritis
Keywords: Mesenchymal stem cells
interleukin-2
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2022-11-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Response rates in both groups （CR and RR）
timeFrame: 24 Weeks
Secondary outcomes:
measure: Time for both groups of subjects to achieve PR and CR
timeFrame: 24 Weeks
measure: SRI response status
timeFrame: 24 Weeks
measure: SLEDAI-2K score and change from baseline
timeFrame: Baseline, Week 4, 8, 16, 20 and 24
measure: BILAG-2004 score and change from baseline
timeFrame: Baseline, Week 4, 8, 16, 20 and 24
measure: Hormone dosage and change from baseline
timeFrame: Baseline, Week 4, 8, 16, 20 and 24
measure: Patient incidence of Treatment-Emergent Adverse Events
timeFrame: 24 Weeks
measure: Patient incidence of Serious adverse events
timeFrame: 24 Weeks
measure: Number of patients with significant changes in laboratory values
timeFrame: 24 Weeks
measure: Number of patients with significant changes in vital signs
timeFrame: 24 Weeks
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Jun Liang, Doctor
role: STUDY_CHAIR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Huayong Zhang, Doctor
role: STUDY_DIRECTOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Cheng Zhao, Doctor
role: STUDY_DIRECTOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Linyu Geng, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Xue Xu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Xiaolei Ma, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Lihui Wen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Saisai Huang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Yunxia Yan, Master
role: PRINCIPAL_INVESTIGATOR
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