NCT03580291

Human Umbilical Cord Mesenchymal Stem Cells Treatment for Lupus Nephritis (LN)

A Randomized, Double-Blind, Parallel-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Human Umbilical Cord Mesenchymal Stem Cells in Patients With Lupus Nephritis

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 230 (estimated)
• Sponsor: Lingyun Sun · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

Lupus nephritis (LN) is one of the most serious complications and the main cause of death in patients with systemic lupus erythematosus (SLE).The investigators have investigated the usefulness, and confirmed the efficacy and safety of mesenchymal stem cells (MSC) treatment of LN in animal models, in vitro experiments and phase I clinical trial. In this study, a randomized, placebo-controlled, parallel group, non-inferiority, prospective, multicenter clinical trial is performed to investigate the efficacy and safety of MSC transplantation in the treatment of LN compared to mycophenolate mofetil (MMF).

Detailed description

Lupus nephritis (LN) is one of the most serious complications and the main cause of death in patients with systemic lupus erythematosus (SLE). Type III, type IV and type V LN are severe clinical entities with poor prognosis, and its treatment remains challenging. Currently, type III, type IV, type V, type III plus V and type IV plus V LN are treated mainly according to the guidelines developed by KDIGO and the European Association for Anti-Rheumatism and European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERAEDTA). The main therapeutic regimens recommended by these guidelines include glucocorticoid combined with immunosuppressants such as cyclophosphamide (CTX), mycophenolate mofetil (MMF), etc. These medications can significantly induce disease remission and improve the long-term survival. However, some patients do not adequately response to the treatment of the combination of steroids and immunosuppressants, and the disease activity cannot be well-controlled. The high prevalence of steroids and immunosuppressants related adverse effects, such as steroid-related diabetes, bone necrosis, hypertension, peptic ulcer, CTX-related bone marrow and gonadal suppression, MMF-related infection risk and so on, have been found in long-term follow-up study. In addition, to date, there is insufficient data to support the use of new biologics, such as rituximab and abatacept in the induction therapy in patients with LN. Mesenchymal stem cells (MSCs) can be obtained from several tissues and possess multiple differentiation potencies and immunomodulatory effects. The investigators have investigated the usefulness, and confirmed the efficacy and safety of MSC treatment of LN in animal models, in vitro experiments and phase I clinical trial. The studies also for the first time found that the MSC abnormalities are involved in the onset and development of lupus both in the lupus mice model and in SLE patients. The investigators found that the efficacy of allogeneic (xenogeneic) MSC transplantation is superior to autologous MSC transplantation in LN mice model. Thus, in current opinion, SLE is not only a hematopoietic stem cell disease, but also a mesenchymal stem cell disease. The investigators treated the refractory LN patients with allogenic MSC treatment, the outcomes revealed that the total response rate was 60%, the mortality rate of 2 to 5 years decreased from 35% - 45% to 6%. These results strongly support the use of allogenic MSC transplantation in the refractory LN patients. The mechanisms of MSC treatment include correcting the immune unbalance, inducing immune tolerance, tissue repair and the improvement of organ function. Allogeneic MSC transplantation for the treatment of SLE and other refractory autoimmune diseases have shown significant efficacy and excellent safety. However, these studies have limitations due to the lack of large-scale, multi-center, randomized, controlled, prospective study to further confirm the efficacy of allogeneic MSC transplantation, as well as the guideline for MSC treatment in SLE needs to be developed. Therefore, a randomized, placebo-controlled, parallel group, non-inferiority, prospective, multicenter clinical trial is urgent needed to promote the application of MSC transplantation in SLE treatment, to bring the benefit of the patients with SLE.

Conditions

• Lupus Nephritis

Interventions

Type	Name	Description
OTHER	Mesenchymal stem cells	The group receive pulse infusion of MSCs once of 2 x 10\^6/kg body weight
DRUG	Mycophenolate Mofetil	This group receive oral MMF of 2.0 g / d.
OTHER	Placebo of Mesenchymal stem cells	The group receive placebo of Mesenchymal stem cells.
DRUG	Placebo of Mycophenolate Mofetil	The group receive placebo of oral mycophenolate mofetil.

Timeline

• Start date: 2018-08-01
• Primary completion: 2021-06-01
• Completion: 2021-06-01
• First posted: 2018-07-09
• Last updated: 2018-07-10

Locations

1 site across 1 country: China