Using stem cells to treat lupus nephritis

Phase II, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate Safety and Efficacy of Mesenchymal Stem Cells (MSV-allo) in the Treatment of Lupus Nephritis

This study is testing if bone marrow stem cells can help adults with lupus nephritis who haven't responded well to regular treatments feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Red de Terapia Celular (industry)
• Drugs / interventions: rituximab, belimumab, ocrelizumab, cyclophosphamide
• Locations: 1 site (Valladolid, Valladolid)
• Trial ID: NCT03673748 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of mesenchymal stem cells (MSCs) derived from bone marrow for treating adults with active proliferative lupus nephritis. It is a Phase 2b, double-blind, placebo-controlled, randomized trial where participants who have not adequately responded to standard treatment will receive either MSCs or a placebo via intravenous injection. The goal is to determine if MSCs can lead to a full or partial response during the induction period of lupus nephritis treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of systemic lupus erythematosus and lupus nephritis who have not responded or have only partially responded to standard treatment.

Not a fit: Patients who have not been diagnosed with lupus nephritis or those who have not experienced a partial or no response to standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with lupus nephritis who do not respond to existing therapies.

How similar studies have performed: Other studies using mesenchymal stem cells for autoimmune diseases have shown promise, but this specific approach for lupus nephritis is still being evaluated.

Eligibility criteria

INCLUSION CRITERIA:

1. Females or males ≥18 years old who provide written informed consent at the selection visit.
2. Diagnosis of systemic lupus erythematosus (SLE) by meeting at least 4 of the 11 criteria included in the American College of Rheumatology (ACR) classification and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, at the selection visit.
3. Diagnosis of lupus nephritis (LN) using the 2003 classification of the International Society of Nephrology and the Society of Renal Pathology, by biopsy performed no more than 6 months before the selection visit if they enter from the induction period, 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 recurrence of lupus nephritis.
5. SLEDAI-2K ≥ 10 during the selection period.
6. Women of childbearing potential should use effective methods of contraception to prevent pregnancy.
7. Have been vaccinated against pneumococcus and influenza at the time the vaccination campaign 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 the Spanish Society of Internal Medicine and the Spanish Society of Nephrology.
2. Use of rituximab, belimumab, ocrelizumab or other biologic therapies against B cells in 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 to selection.
5. Use of immunoglobulins in the 6 months prior to selection.
6. Change in doses of an angiotensin converting enzyme inhibitor or an angiotensin receptor inhibitor in the two months prior to selection.
7. Treatment with another investigational medicinal product within three months prior to 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 the opinion of the investigator, the sponsor or the person they designate, constitutes an inappropriate risk or a contraindication for participation in the trial or that could interfere with the objectives of the trial, its performance or evaluation.
9. Cardiac, peripheral, or cerebrovascular cardiovascular events in the 6 months prior to the selection visit.
10. Active cardiac arrhythmia or clinically significant electrocardiogram abnormalities at selection visit or on the day of randomization that, in the opinion of the investigator, sponsor, or designee, constitute an inappropriate risk or contraindication to participation in the study.
11. Thromboembolic events in the 12 months prior to or during selection, whether or not associated with associated antiphospholipid syndrome, or inadequate anticoagulation tests 6 weeks immediately prior to or during selection visit.
12. Active central nervous system SLE that is considered severe or progressive (recent uncontrolled seizures, changes in anticonvulsant treatment within 3 months prior to selection visit, or resulting in significant cognitive impairment).
13. History or current diagnosis of a demyelinating disease such as multiple sclerosis or optic neuritis.
14. Comorbidities that require treatment with systemic corticosteroids (oral, rectal or injectable) 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 having suffered a major episode of infection that required hospitalization or parenteral treatment 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 during selection, or a history of recurrent infections (three or more cases of the same type of infection in a consecutive 12-month period). Controlled vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus would not be reasons for exclusion.
17. History of or positive human immunodeficiency virus (HIV) test result, hepatitis C antibodies and/or detection by polymerase chain reaction, hepatitis B surface antigen (HBsAg+), and/or IgM or total antibodies against hepatitis B nuclear antigen at selection.
18. Diagnosis of active or latent tuberculosis (TB) using a purified protein derivative TB skin test (induration ≥ 5 mm) or a positive Quantiferon test result, at selection or within 3 months prior to the selection visit. Patients who have completed previous adequate treatment or who are receiving treatment will not repeat the test. Patients who are receiving adequate TB treatment for at least 4 continuous weeks prior to the selection visit and who are expected to complete the treatment regimen will not be excluded.
19. Presence of class 3 or 4 uncontrolled congestive heart failure according to the New York Heart Association.
20. Active cancer.
21. Major surgical intervention within 6 weeks prior to selection visit or planned during 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 have been performed within 3 months prior to the selection visit or during the selection period.

    D - Others:
25. Legal incapacity.

Where this trial is running

Valladolid, Valladolid

• University Hospital Río Hortega — Valladolid, Valladolid, Spain (RECRUITING)

Study contacts

• Principal investigator: Margarita González-Vallinas, PhD — University of Valladolid
• Study coordinator: Julia Barbado, MD, PhD

Conditions: Lupus Nephritis, Lupus Erythematosus, Stem Cell, Mesenchymal Stem Cells, Autoimmune diseases, Systemic Lupus Erythematosus