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

November 20, 2022 updated by: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210008
        • Recruiting
        • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rates in both groups （CR and RR）
Time Frame: 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.
24 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time for both groups of subjects to achieve PR and CR
Time Frame: 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.
24 Weeks
SRI response status
Time Frame: 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.
24 Weeks
SLEDAI-2K score and change from baseline
Time Frame: Baseline, Week 4, 8, 16, 20 and 24
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
Time Frame: Baseline, Week 4, 8, 16, 20 and 24
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
Time Frame: 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
Baseline, Week 4, 8, 16, 20 and 24
Patient incidence of Treatment-Emergent Adverse Events
Time Frame: 24 Weeks
To characterize the safety of MSCs and IL-2
24 Weeks
Patient incidence of Serious adverse events
Time Frame: 24 Weeks
To characterize the safety of MSCs and IL-2
24 Weeks
Number of patients with significant changes in laboratory values
Time Frame: 24 Weeks
To characterize the safety of MSCs and IL-2
24 Weeks
Number of patients with significant changes in vital signs
Time Frame: 24 Weeks
To characterize the safety of MSCs and IL-2
24 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2022

Primary Completion (Anticipated)

June 1, 2025

Study Completion (Anticipated)

December 31, 2025

Study Registration Dates

First Submitted

November 13, 2022

First Submitted That Met QC Criteria

November 20, 2022

First Posted (Actual)

November 30, 2022

Study Record Updates

Last Update Posted (Actual)

November 30, 2022

Last Update Submitted That Met QC Criteria

November 20, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-LCYJ-MS-38

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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