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

NCT03580291 | Unknown Phase 2 DMC

• 1 other identifier: 2017001
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Lupus Nephritis

Keywords

Lupus Nephritis; Mesenchymal stem cell

Outcome Measures

Primary Outcomes (1)

• Total remission rate

  Complete remission rate (CR) and partial remission rate (PR)

  weeks 24

Secondary Outcomes (17)

• The time for subjects of the two groups to achieve PR and CR

  Baseline to weeks 24

• Levels of 24-hour urinary protein

  Baseline, weeks 4, 8, 12, 16, 20, 24

• Ratio of Urinary Protein / Creatinine

  Baseline, weeks 4, 8, 12, 16, 20, 24

• Levels of serum albumin

  Baseline, weeks 4, 8, 12, 16, 20, 24

• Levels of serum creatinine

  Baseline, weeks 4, 8, 12, 16, 20, 24

Study Arms (2)

Mesenchymal stem cells

EXPERIMENTAL

The group receive pulse infusion of MSCs and placebo of oral Mycophenolate Mofetil (MMF). The cells of 2 x 10\^6/kg body weight are suspended in 100ml saline and infused intravenously. 1. Dexamethasone of 10mg is intravenously injected before 30 minutes of cells infusion. 2. A sterile blood transfusion device is used during the venous transfusion, and it is washed with saline before infusion. Take a slow infusion of about 20 drops per minute in the first 15 minutes. Increase to about 60 drops per minute if the patient had no complaints of discomfort.

Other: Mesenchymal stem cells; Drug: Placebo of Mycophenolate Mofetil

Mycophenolate Mofetil

ACTIVE COMPARATOR

The group receive placebo of MSCs and oral Mycophenolate Mofetil of 2.0g/d. .

Drug: Mycophenolate Mofetil; Other: Placebo of Mesenchymal stem cells

Interventions

Mesenchymal stem cells OTHER

The group receive pulse infusion of MSCs once of 2 x 10\^6/kg body weight

Mesenchymal stem cells

Mycophenolate Mofetil DRUG

This group receive oral MMF of 2.0 g / d.

Mycophenolate Mofetil

Placebo of Mesenchymal stem cells OTHER

The group receive placebo of Mesenchymal stem cells.

Mycophenolate Mofetil

Placebo of Mycophenolate Mofetil DRUG

The group receive placebo of oral mycophenolate mofetil.

Mesenchymal stem cells

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who met the American college of Rheumatology (ACR, 1997) classification criteria for SLE;
• Ages: 18-60 years old (including);
• Presence of class III, IV, V, III+V or IV+V LN as determined by renal biopsy within 12 weeks of randomization(2003 ISN/RPS LN classification criteria);
• Morning proteinuria /creatinine ratio \>1.0 or 24 hours Proteinuria \>1.0g, with or without microscopic hematuria(\>5 red blood cells/high-power field);
• Women of childbearing age agreed to adopt effective contraception measures during the trial period;
• Urine pregnancy tests were negative in women of childbearing age;
• Subject signed the informed consent form voluntarily and complied with the requirements of the research program.

You may not qualify if:

• Received MMF, CTX, other potent immunosuppressive agents (including cyclosporine, tacrolimus, Tripterygium wilfordii and leflunomide) or biologics (Rituximab or others) within the past 12 weeks.
• Previous failure to respond to MMF.
• Known intolerance to MMF.
• Renal biopsy showing ≥50% glomerulus sclerosis.
• Renal biopsy showing capillary loops necrosis, microthrombus formation in capillary loops, or cellular crescent in ≥50% of glomeruli.
• Patients diagnosed with other autoimmune diseases apart from SLE: dermatomyositis/polymyositis, mixed connective tissue disease, scleroderma, rheumatoid arthritis, etc. However, participants with secondary Sjogren's syndrome are allowed to take part in the study.
• Patients suffering from severe liver or kidney dysfunction (total bilirubin more than 14mg/L, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal lab value; creatinine clearance rate (Ccr) \< 30ml/min or serum creatinine (Scr) ≥265.2umol/L).
• Patients with hematological abnormalities (white blood cell \<3000/uL, hemoglobin \<8g/dL, and/or platelets \<50000/uL).
• Patients diagnosed with severe or uncontrolled cardiovascular, neurological, pulmonary (including obstructive pulmonary disease and interstitial lung disease), hepatic, endocrine (including uncontrolled diabetes mellitus), and gastrointestinal disorders.
• Known active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis, atypical mycobacterial infection, granulomatous disease showed by chest X-ray, hepatitis B, hepatitis C, HIV infection and herpes zoster, whereas not including onychomycosis). Any infection requiring hospitalization within 4 weeks prior to enrollment or intravenous antimicrobial treatment within 2 weeks prior to randomization.
• History of malignancy, including solid tumor and hematologic malignancies (except basal cell carcinoma which has been excised or successfully treated).
• Women who are pregnant or breastfeeding.

Sponsors & Collaborators

• Lingyun Sun: lead

Study Sites (1)

The Affiliated Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

Location

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Central Study Contacts

Lingyun Sun, Ph.D M.D.

CONTACT

+86(025)83106666; lingyunsun@nju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Department of Rheumatology and Immunology

Study Record Dates

• First Submitted: January 12, 2018
• First Posted: July 9, 2018
• Study Start: August 1, 2018
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

CN (1)