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

Systemic Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05631717
• Other study ID #: 2022-LCYJ-MS-38
• Status: Recruiting
• Phase: Phase 3
• Start date: October 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: September 2022
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: Jun Liang, Doctor
• Phone: 13505193169
• Email: 13505193169[@]139.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Lupus Nephritis
• Nephritis
• Systemic Lupus Erythematosus

Intervention

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.

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.

Locations

Country	Name	City	State
China	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Erratum In: Ann Rheum Dis. 2011 Jan;70(1):237. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Patient incidence of Treatment-Emergent Adverse Events	To characterize the safety of MSCs and IL-2	24 Weeks
Secondary	Patient incidence of Serious adverse events	To characterize the safety of MSCs and IL-2	24 Weeks
Secondary	Number of patients with significant changes in laboratory values	To characterize the safety of MSCs and IL-2	24 Weeks
Secondary	Number of patients with significant changes in vital signs	To characterize the safety of MSCs and IL-2	24 Weeks