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

NCT05631717 | Unknown Phase 3 DMC

• 1 other identifier: 2022-LCYJ-MS-38
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

Systemic Lupus Erythematosus; Lupus Nephritis

Keywords

Mesenchymal stem cells; interleukin-2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Time for both groups of subjects to achieve PR and CR

  24 Weeks

• SRI response status

  24 Weeks

• SLEDAI-2K score and change from baseline

  Baseline, Week 4, 8, 16, 20 and 24

• BILAG-2004 score and change from baseline

  Baseline, Week 4, 8, 16, 20 and 24

• Hormone dosage and change from baseline

  Baseline, Week 4, 8, 16, 20 and 24

Study Arms (2)

MSCs group

EXPERIMENTAL

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

IL-2 group

EXPERIMENTAL

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

Interventions

Human umbilical cord mesenchymal stem cells BIOLOGICAL

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

MSCs group

Interleukin-2 DRUG

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.

Also known as: Recombinant Human Interleukin-2(1) for Injection

IL-2 group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (1)

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

RECRUITING

Related Publications (12)

• Geng L, Xu X, Zhang H, Chen C, Hou Y, Yao G, Wang S, Wang D, Feng X, Sun L, Liang J. Comprehensive expression profile of long non-coding RNAs in Peripheral blood mononuclear cells from patients with neuropsychiatric systemic lupus erythematosus. Ann Transl Med. 2020 Mar;8(6):349. doi: 10.21037/atm.2020.03.25.

  PMID: 32355793 BACKGROUND

• Liang J, Zhang H, Kong W, Deng W, Wang D, Feng X, Zhao C, Hua B, Wang H, Sun L. Safety analysis in patients with autoimmune disease receiving allogeneic mesenchymal stem cells infusion: a long-term retrospective study. Stem Cell Res Ther. 2018 Nov 14;9(1):312. doi: 10.1186/s13287-018-1053-4.

  PMID: 30428931 BACKGROUND

• Zhang H, Liang J, Qiu J, Wang F, Sun L. Ultrasonographic evaluation of enthesitis in patients with ankylosing spondylitis. J Biomed Res. 2017 Jan 19;31(2):162-169. doi: 10.7555/JBR.31.20160088.

  PMID: 28808198 BACKGROUND

• Zhang H, Liang J, Tang X, Wang D, Feng X, Wang F, Hua B, Wang H, Sun L. Sustained benefit from combined plasmapheresis and allogeneic mesenchymal stem cells transplantation therapy in systemic sclerosis. Arthritis Res Ther. 2017 Jul 19;19(1):165. doi: 10.1186/s13075-017-1373-2.

  PMID: 28724445 BACKGROUND

• Liang J, Zhang H, Zhao C, Wang D, Ma X, Zhao S, Wang S, Niu L, Sun L. Effects of allogeneic mesenchymal stem cell transplantation in the treatment of liver cirrhosis caused by autoimmune diseases. Int J Rheum Dis. 2017 Sep;20(9):1219-1226. doi: 10.1111/1756-185X.13015. Epub 2017 Feb 20.

  PMID: 28217916 BACKGROUND

• Chen C, Liang J, Yao G, Chen H, Shi B, Zhang Z, Zhao C, Zhang H, Sun L. Mesenchymal stem cells upregulate Treg cells via sHLA-G in SLE patients. Int Immunopharmacol. 2017 Mar;44:234-241. doi: 10.1016/j.intimp.2017.01.024. Epub 2017 Jan 25.

  PMID: 28129605 BACKGROUND

• Liang J, Wang F, Wang D, Zhang H, Zhao C, Wang S, Sun L. Transplantation of mesenchymal stem cells in a laryngeal carcinoma patient with radiation myelitis. Stem Cell Res Ther. 2015 Nov 4;6:213. doi: 10.1186/s13287-015-0203-1.

  PMID: 26537898 BACKGROUND

• Liang J, Sun L. Mesenchymal stem cells transplantation for systemic lupus erythematosus. Int J Rheum Dis. 2015 Feb;18(2):164-71. doi: 10.1111/1756-185X.12531. Epub 2015 Jan 22.

  PMID: 25611801 BACKGROUND

• Liang J, Zhang H, Wang D, Feng X, Wang H, Hua B, Liu B, Sun L. Allogeneic mesenchymal stem cell transplantation in seven patients with refractory inflammatory bowel disease. Gut. 2012 Mar;61(3):468-9. doi: 10.1136/gutjnl-2011-300083. Epub 2011 May 26. No abstract available.

  PMID: 21617158 BACKGROUND

• Liang J, Li X, Zhang H, Wang D, Feng X, Wang H, Hua B, Liu B, Sun L. Allogeneic mesenchymal stem cells transplantation in patients with refractory RA. Clin Rheumatol. 2012 Jan;31(1):157-61. doi: 10.1007/s10067-011-1816-0. Epub 2011 Aug 12.

  PMID: 21837432 BACKGROUND

• Liang J, Zhang H, Hua B, Wang H, Lu L, Shi S, Hou Y, Zeng X, Gilkeson GS, Sun L. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis. 2010 Aug;69(8):1423-9. doi: 10.1136/ard.2009.123463.

  PMID: 20650877 BACKGROUND

• Liang J, Gu F, Wang H, Hua B, Hou Y, Shi S, Lu L, Sun L. Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE. Nat Rev Rheumatol. 2010 Aug;6(8):486-9. doi: 10.1038/nrrheum.2010.80. Epub 2010 Jun 1.

  PMID: 20517294 BACKGROUND

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Interventions

Interleukin-2; WW Domain-Containing Oxidoreductase

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins

Study Officials

• Jun Liang, Doctor

  The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

  STUDY CHAIR

• 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

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Liang, Doctor

CONTACT

13505193169; 13505193169@139.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 13, 2022
• First Posted: November 30, 2022
• Study Start: October 1, 2022
• Primary Completion: June 1, 2025
• Study Completion: December 31, 2025
• Last Updated: November 30, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)