Mesenchymal Stem/Stromal Cells: INTERIM REPORT FROM THE NEPHSTROM MULTI-CENTRE, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE-1B CLINICAL TRIAL OF A NOVEL MESENCHYMAL STROMAL CELL THERAPY IN PROGRESSIVE DIABETIC KIDNEY DISEASE
Cytotherapy
; 24(5):S50-S51, 2022.
Article
in English
| EMBASE | ID: covidwho-1996714
ABSTRACT
Background & Aim:
Funded in 2015, the NEPHSTROM EU-H2020 consortium aimed to translate pre-clinical evidence of efficacy of “off-the-shelf” intravenous (i.v.) allogeneic mesenchymal stromal cells (allo-MSC) in diabetic nephropathy to early-phase clinical investigation in patients with progressive diabetic kidney disease (DKD). Methods, Results &Conclusion:
Methods:
The trial IMP, NEPHSTROM ORBCEL-M, consists of cryopreserved, CD362-selected bone marrow allo-MSCs or matching placebo (cryopreservation fluid). The protocol for a multi-site, randomised, placebo-controlled, double- blind, dose-escalation phase-1b clinical trial in adults with DKD due to type 2 diabetes was designed collaboratively by a group of academic nephrologists and cell therapy specialists from Italy, the UK, Ireland and the Netherlands. Inclusion criteria included age 40-85 yrs and type 2 diabetes with evidence of progressive DKD [eGFR 25- 55mL/min/1.73m2, urine albumin creatinine ratio >88mg/g and rapid eGFR decline or ≥15% risk of ESRD within 5 years]. Three dose cohorts were planned, each with n=12 NEPHSTROM ORBCEL-M recipients + n=4 Placebo recipients and 18 months follow-up.Results:
Following regulatory approval of the trial dossier through the EMA’s Voluntary Harmonisation Procedure and ethical approvals at the Sponsor site (Bergamo, Italy) and three other sites (Galway, Ireland;Birmingham and Belfast, UK), the NEPHSTROM trial (NCT02585622) opened March 2018. To date, 27 patients have been treated and 14 have completed the trial protocol. We report here our (as-yet blinded) experiences with the first fixed-dose cohort (80x10e6 cells/placebo i.v.), consisting of 16 subjects enrolled at 3 sites and followed for 18 months. The trial intervention proved safe, with one quickly-resolved infusion reaction and no subsequent SAEs ascribed to the IMP. Two patients died of unrelated causes between 12 and 18 months. Serial serum assays for anti-HLA antibodies indicated no persistent allo-immune sensitisation. NEPHSTROM ORBCEL-M effects on trends in eGFR, true GFR (iohexol clearance), albuminuria, serum/plasma inflammatory biomarkers and immune cell profiles will be analysed after unblinding. Following DSMB approval and COVID-19-related trial pauses, 11 second dose cohort subjects (160x10e6 cells/placebo i.v.) have been treated and are undergoing follow-up with no IMP-related adverse events to date.Conclusion:
A novel, off-the-shelf, i.v. allo-MSC IMP has thus far proven safe and feasible in adults with progressive DKD.
biological marker; endogenous compound; HLA antibody; iohexol; placebo; syndecan 2; adult; albumin to creatinine ratio; albuminuria; bone marrow; cell therapy; clinical article; clinical trial; cohort analysis; conference abstract; controlled study; coronavirus disease 2019; cryopreservation; diabetic nephropathy; double blind procedure; end stage renal disease; estimated glomerular filtration rate; female; follow up; glomerulus filtration rate; human; human cell; human tissue; immunocompetent cell; intravenous drug administration; Ireland; Italy; male; mesenchymal stromal cell therapy; multicenter study; nephrologist; Netherlands; non insulin dependent diabetes mellitus; phase 1 clinical trial; randomized controlled trial; sensitization
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Language:
English
Journal:
Cytotherapy
Year:
2022
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS