During the first part of the project, the clinical study documents was approved from ethics committees and the national competent authorities in France, Italy, Spain and Germany. The clinical trial has also been registered in the international registry for clinical trials under the EudraCT number 2017-002092-25 (www.clinicaltrials.gov).
Procedures including cells expansion, cell cryopreservation and transportation of cellular treatments have been effectively optimized. The cell producer centre (beneficiary 6 / Citospin) successfully produced all batches of MSCs using bone marrow from healthy donors.
All the Standard Operating Procedures (SOP) have been drafted, and setup visits have been completed in all nine clinical centres across France (4 centres), Italy (1 centre), Spain (3 centres) and Germany (1 centre). The first patients enrolled in the RESPINE trial received their injections in March 2019. By May 2021, a total of 112 expected patients had undergone treatment with either allogeneic adult BM-MSCs therapy or a sham treatment. The execution of logistical processes, including the timely transport of cells from the cellular production centre to various clinical centres and the centralized reading validation of MRI scans for patient inclusion, proceeded without any significant setbacks.
During the last period, all patients completed visits at months 6, 12, and 24, and the RESPINE clinical trial ended in April 2023. No Serious Adverse Events (SEAs) with life-threatening impact were noted. The overall benefit/risk ratio remained positive throughout the treatment period. Remarkably, 74% of patients experienced improvement in both pain and functional scores, although the study did not reach the primary endpoint. Clinical improvements were observed in pain scores as well as in mental scores (SF36) at the 12-month.
In parallel, immune response analyses were conducted, measuring anti HLA antibodies in the serum of 50 BM-MSCs-treated patients at both month 0 and month 6. Positive cases were further characterized to identify donor-specific antibodies (DSA). A robust, reproducible, and accurate growth factor-based induction protocol was established to generate nucleopulpocyte like cells from human BM-MSCs.
The RESPINE team has disseminated findings through 5 publications in peer-reviewed journals and press articles. The final publication on clinical results is currently under review. Throughout the RESPINE project, the consortium shared its results at various international congresses. A comprehensive presentation of all results took place during the final workshop held in Montpellier on 13th June 2023.
