LUPUS NEPHRITIS MedDRA version: 20.0 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: CÉLULAS MESENQUIMALES TRONCALES ADULTAS ALOGÉNICAS DE MÉDULA ÓSEA EXPANDIDAS BAJO PROCEDIMIENTO GMP
Product Code: CÉLULAS MESENQUIMALES
Pharmaceutical Form: Solution for injection/infusi
Sponsors
INSTITUTO DE ESTUDIOS DE CIENCIAS DE LA SALUD DE CASTILLA Y LEON
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female = 18 yrs with written informed consent. 2. SLE diagnosis fulfiilling at least 4 out of the 11 ACR criteria during the course of their illness. 3. Diagnosis of LN class (2003 classification by International Society of Nephrology/Renal Pathology Society) by biopsy less than 6 months prior. 4. No response or partial response to induction therapy after at least three months with cyclophosphamide (750 mg/m² body surface/mo) or mycophenolat mofetil (2-2.5 gr/day) or mycophenolate sodium (1.040-1.800 mg/day) plus corticoids = 40 mg per day. Complete response criteria is: glomerular filtration rate = 60 ml/min/1,73m², or decline to baseline or ± 15% of baseline in those with glomerular filtration rate 3gr/d. Partial response means patients with basal proteinuria = 3.5 g in 24 h that declines 50%; stabilization or improvement of glomerular filtration rate in both situations. SLEDAI-2K score = 6 at selection period. 5. Women subjects of childbearing potential must use a highly effective method of contraception to prevent pregnancy. 6. History of vaccinations against S. pneumococcus, H. influenza and seasonal vaccinations, as required. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Use of corticoids, mycophelolate, cyclophosphamide above doses permitted for induction, according to the Consensus Document of the Group of Systemic Autoimmune Diseases of the Spanish Society of Internal Medicine and the Spanish Society of Nephrology. 2. Use of rituximab, belimumab or ocrelizumab, or other B cell-directed biologic therapies within 1 yr before treatment. 3. Use of abatacept within 1 yr before treatment. 4. Use of any tumor necrosis factor (TNF) inhibitor therapy within 1 yr before selection. 5. Use of immunoglobulin treatment within 1 yr before treatment. 6. Change in dosage of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) within 2 months before treatment. 7. Treatment with other investigational agents within the last 3 months or 5 half-lives prior to treatment. 8. Exclusion criteria related to medical conditions: a. Any condition that in the investigator´s opinion constitutes an unnecessary risk or a counterindication for participation. b. History of or planned renal or other organ transplant. c. Positive human immunodeficiency virus or hepatitis C Ab and/or PCR, or hepatitis B surface antigen (+), or hepatitis B cIgG and/or IgM Ab(+) with (-) hepatitis B sAb. d. Diagnosis of active tuberculosis, or latent tuberculosis infection. e. History of cancer. f. History of major surgery within 6 months prior to treatment. g. Lactating women. h. Legal incapacity or limited legal capacity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy of MSCs in achieving a full or partial response in the treatment of LN during its induction period. Complete response criteria is: glomerular filtration rate = 60 ml/min/1,73m², or decline to baseline or ± 15% of baseline in those with glomerular filtration rate 3gr/d. Partial response means patients with basal proteinuria = 3.5 g in 24 h that declines 50%; stabilization or improvement of glomerular filtration rate in both situations.;Secondary Objective: 1. To calculate the time it takes to achieve partial/full response after MSCs infusion. 2. To time duration of the response. 3. To determine the efficacy of MSCs in reducing corticosteroid and immunosuppressant usage. 4. To evaluate the safety, tolerability and immunogenicity profiles of MSCs in SLE subjects. 5. To monitor the effect of MSCs on patient-reported outcomes. Exploratory objectives are: 6. To observe the changes of T cells populations (naive, central memory, memory/effector, effector),T cell subpopulations CD4 (Th1, Th2, Treg, Th17, TFH), B cells populations (maduration, effector and memory cells) and leukocyte subsets after MSCs infusion. 7. To identify the associations between the profiles of circulating proteins with MSCs response, efficacy and safety. 8. To monitor the changes in MSCs properties from healthy donors cultured in plasma of lupus subjects.;Primary end point(s): The primary endpoint is the proportion of subjects who have achieved the full or partial response at week 24 compared to the screening visit. Complete response criteria: glomerular filtration = 60ml / min / 1.73m², or decrease to baseline or ± 15% of baseline in those with glomerular filtration 3 g / dl. Partial response criteria: baseline proteinuria = 3.5 g / 24h, decrease in proteinuria 50% compared to baseline; In both situations stabilization (± 25%) or improvement of glomerular filtration with respect to initial values. Decrease in at least 4 poin | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: During 18 months the patient will be monitored with the objective of detecting treatment effectiveness after 24 weeks post-administration, adverse effects or progression of the disease. Patients will enter this period directly from the treatment period after the week 24 visit. The safety visits will be performed each month. During this period, efficacy will be assessed using clinical and analytical parameters for NL, and various activity indexes including BILAG 2004, SLEDAI-2K, SRI-50 index and PGA. As part of the evaluation, SF-36 and Lupus QoL quality of life questionnaires are included. In addition, changes in laboratory parameters, vital signs, ECG and symptoms along with exploratory findings will be evaluated.;Secondary end point(s): 1. Proportion of subjects at week 24 whose dose of corticosteroids equivalent to prednisone has been reduced from screening visit by = 25% and to a dose of = 7.5 mg / day and have no BILAG A or 2B flare in disease activity. A BILAG A or 2B flare is defined by at least one new BILAG A organ domain score and/or at least 2 new BILAG B organ domain scores compared to screening visit. 2. Proportion of subjects at each visit whose dose equivalent to prednisone has been reduced from screening visit by = 25% and to a dose of = 7.5 mg / day, and have no BILAG A or 2B flare in disease activity. 3. Proportion of subjects at week 24 with a decrease from screening visit at the daily dose of corticosteroids equivalent to prednisone from 0- 50%, or an increase. 4. Cumulative dose of corticosteroids equivalent to prednisone from screening visit until completion of the treatment period. 5. Proportion of subjects who before the 24th week have started with the maintenance treatment and who do not present any BILAG A or 2B flare. Variables of global disease activity 6. Time it takes to achieve complete remission after PEI administration. 7. Time the response lasts from the complete or partial response to | — |
Countries
Spain
Contacts
Public ContactIESCyL
INSTITUTO DE ESTUDIOS DE CIENCIAS DE LA SALUD DE CASTILLA Y LEON
Outcome results
None listed