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

Sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (Other)

Overall Status

Recruiting

CT.gov ID

NCT05631717

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus Lupus Nephritis	Biological: Human umbilical cord mesenchymal stem cells Drug: Interleukin-2	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MSCs group 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 Human umbilical cord mesenchymal stem cells (1 × 10 ^6 cells / kg body weight, suspended in 30ml saline), intravenous drip once.
Experimental: IL-2 group 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 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. Other Names: Recombinant Human Interleukin-2(1) for Injection

Arm

Intervention/Treatment

Experimental: MSCs group

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

Human umbilical cord mesenchymal stem cells (1 × 10 ^6 cells / kg body weight, suspended in 30ml saline), intravenous drip once.

Experimental: IL-2 group

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

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.

Other Names:

Recombinant Human Interleukin-2(1) for Injection

Outcome Measures

Primary Outcome Measures

Response rates in both groups （CR and RR） [24 Weeks]
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.

Secondary Outcome Measures

Time for both groups of subjects to achieve PR and CR [24 Weeks]
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.
SRI response status [24 Weeks]
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.
SLEDAI-2K score and change from baseline [Baseline, Week 4, 8, 16, 20 and 24]
To describe the effect of treatment with MSCs or IL-2 using patient reported outcomes
BILAG-2004 score and change from baseline [Baseline, Week 4, 8, 16, 20 and 24]
To describe the effect of treatment with MSCs or IL-2 using patient reported outcomes
Hormone dosage and change from baseline [Baseline, Week 4, 8, 16, 20 and 24]
To describe the effect of treatment with MSCs or IL-2 using dose of hormones in patients
Patient incidence of Treatment-Emergent Adverse Events [24 Weeks]
To characterize the safety of MSCs and IL-2
Patient incidence of Serious adverse events [24 Weeks]
To characterize the safety of MSCs and IL-2
Number of patients with significant changes in laboratory values [24 Weeks]
To characterize the safety of MSCs and IL-2
Number of patients with significant changes in vital signs [24 Weeks]
To characterize the safety of MSCs and IL-2

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School	Nanjing	Jiangsu	China	210008

Sponsors and Collaborators

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Investigators

Study Chair: Jun Liang, Doctor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Study Director: Huayong Zhang, Doctor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Study Director: Cheng Zhao, Doctor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Principal Investigator: Linyu Geng, Doctor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Principal Investigator: Xue Xu, Doctor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Principal Investigator: Xiaolei Ma, Doctor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Principal Investigator: Lihui Wen, Doctor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Principal Investigator: Saisai Huang, Doctor, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Principal Investigator: Yunxia Yan, Master, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School