Treatment of Lupus Nephritis With Allogeneic Mesenchymal Stem Cells

INCLUSION CRITERIA:

1. Females or males ≥18 years old who provide written informed consent at the selectionvisit.

2. Diagnosis of systemic lupus erythematosus (SLE) by meeting at least 4 of the 11criteria included in the American College of Rheumatology (ACR) classificationand/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, atthe selection visit.

3. Diagnosis of lupus nephritis (LN) using the 2003 classification of the InternationalSociety of Nephrology and the Society of Renal Pathology, by biopsy performed nomore than 6 months before the selection visit if they enter from the inductionperiod, and no more than one year if they enter with a moderate/severe recurrence.

4. No response or partial response to standard treatment, or moderate/severe recurrenceof lupus nephritis.

5. SLEDAI-2K ≥ 10 during the selection period.

6. Women of childbearing potential should use effective methods of contraception toprevent pregnancy.

7. Have been vaccinated against pneumococcus and influenza at the time the vaccinationcampaign is carried out.

EXCLUSION CRITERIA:

A - Related to previous treatments:

1. Use of corticosteroids or mycophenolate above the doses allowed for induction,according to the Consensus Document of the Systemic Autoimmune Diseases Group of theSpanish Society of Internal Medicine and the Spanish Society of Nephrology.

2. Use of rituximab, belimumab, ocrelizumab or other biologic therapies against B cellsin the 6 months prior to selection.

3. Use of cyclophosphamide in the 6 months prior to selection.

4. Use of any tumor necrosis factor inhibitor treatment in the 6 months prior toselection.

5. Use of immunoglobulins in the 6 months prior to selection.

6. Change in doses of an angiotensin converting enzyme inhibitor or an angiotensinreceptor inhibitor in the two months prior to selection.

7. Treatment with another investigational medicinal product within three months priorto selection or 5 times the half-life of the agent. B - Related to medical problems:

8. Any pathology, including an uncontrolled disease other than SLE, which, in theopinion of the investigator, the sponsor or the person they designate, constitutesan inappropriate risk or a contraindication for participation in the trial or thatcould interfere with the objectives of the trial, its performance or evaluation.

9. Cardiac, peripheral, or cerebrovascular cardiovascular events in the 6 months priorto the selection visit.

10. Active cardiac arrhythmia or clinically significant electrocardiogram abnormalitiesat selection visit or on the day of randomization that, in the opinion of theinvestigator, sponsor, or designee, constitute an inappropriate risk orcontraindication to participation in the study.

11. Thromboembolic events in the 12 months prior to or during selection, whether or notassociated with associated antiphospholipid syndrome, or inadequate anticoagulationtests 6 weeks immediately prior to or during selection visit.

12. Active central nervous system SLE that is considered severe or progressive (recentuncontrolled seizures, changes in anticonvulsant treatment within 3 months prior toselection visit, or resulting in significant cognitive impairment).

13. History or current diagnosis of a demyelinating disease such as multiple sclerosisor optic neuritis.

14. Comorbidities that require treatment with systemic corticosteroids (oral, rectal orinjectable) such as asthma or inflammatory bowel disease.

15. Antecedents or plans for an organ transplant.

16. Clinically significant active viral, bacterial or fungal infection, or havingsuffered a major episode of infection that required hospitalization or parenteraltreatment in the 4 weeks prior to the selection visit, during the selection visit,or having finished anti-infective treatment within 2 weeks prior to or duringselection, or a history of recurrent infections (three or more cases of the sametype of infection in a consecutive 12-month period). Controlled vaginal candidiasis,onychomycosis, and genital or oral herpes simplex virus would not be reasons forexclusion.

17. History of or positive human immunodeficiency virus (HIV) test result, hepatitis Cantibodies and/or detection by polymerase chain reaction, hepatitis B surfaceantigen (HBsAg+), and/or IgM or total antibodies against hepatitis B nuclear antigenat selection.

18. Diagnosis of active or latent tuberculosis (TB) using a purified protein derivativeTB skin test (induration ≥ 5 mm) or a positive Quantiferon test result, at selectionor within 3 months prior to the selection visit. Patients who have completedprevious adequate treatment or who are receiving treatment will not repeat the test.Patients who are receiving adequate TB treatment for at least 4 continuous weeksprior to the selection visit and who are expected to complete the treatment regimenwill not be excluded.

19. Presence of class 3 or 4 uncontrolled congestive heart failure according to the NewYork Heart Association.

20. Active cancer.

21. Major surgical intervention within 6 weeks prior to selection visit or plannedduring the trial period, including follow-up.

22. Pregnant or lactating women. C - Laboratory abnormalities:

23. Clinically significant laboratory test abnormalities not attributed to active SLE.

24. Chest X-ray with significant changes indicating active TB. The chest X-ray must havebeen performed within 3 months prior to the selection visit or during the selectionperiod. D - Others:

25. Legal incapacity.