Report
Teaser, summary, work performed and final results
Periodic Reporting for period 1 - RESPINE (REgenerative therapy of intervertebral disc: a double blind phase 2b trial of intradiscal injection of mesenchymal stromal cells in degenerative disc disease of the lomber SPINE unresponsive to conventional therapy)
Teaser
The World Health Organisation (WHO) has included low back pain in its list of twelve priority diseases. Notably, Degenerative disc disease (DDD) presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is...
Summary
The World Health Organisation (WHO) has included low back pain in its list of twelve priority diseases. Notably, Degenerative disc disease (DDD) presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is available. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated regeneration of adjacent segments.
Our consortium partners have developed and studied stem cell-based, regenerative therapies with encouraging results in phase 2a trials. Patients exhibited rapid and progressive improvement of functional and pain indexes by 50% within 6 months and by 65% to 78% after 1 year with no severe side effects. In addition, MRI T2 relaxation measurements demonstrated a significant improvement.
To develop the world’s first rigorously proven, effective treatment of DDD, RESPINE aims to conduct a clinical trial : A phase 3 prospective, multicentre randomized, double-blind trial, comparing intra-discal allogeneic adult BM-MSC therapy and sham-treated controls in subjects with chronic low back pain due to lumbar degenerative disc disease (DDD) unresponsive to conventional therapy. This innovative therapy aims to rapidly (within 3 months) and sustainably (at least 24 months) reduce pain and disability.
In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection. This simple procedure would be cost-effective, minimally invasive, and standardised.
The transfer to the clinic will be prepared at a affordable cost thanks to the strategy of production of allogenic cells, automation & EU standardisation. At the end of the EUROSPINE trial, we aim to propose a broadly available and clinically applicable treatment for DDD, marketed by European SMEs.
Work performed
All consortium actively participated in the edification of the regulatory files to be submitted for the VHP. Particularly, we took advantage of consortium meeting to share and propose an original strategy for the cryopreservation, which must be a crucial step in the production process. And, we also significantly contributed in the thinking and the elaboration of harmonisation procedure of the selection of the patients, injection and follow up of the patient.
The VHP procedure has been submit in July 2017 and accepted in March 2018, during all this period all partner has actively participate to answer of the Spanish Agency of Medicines and Medical Devices and National Competent Authorities. Ethical approval are obtain for Italy, Spain and France. We are still waiting for the German approval, they need more information on the protocol.
In parallel, partner has actively tested different media for mesenchymal stem cells production and pursued the development of a proprietary define serum free medium which could become strategic in the future for GMP production of clinical grade mesenchymal stem cells. We also design of the additional experiments that studied the bio-distribution of the injected cells needed to complete the IMPD. As the cell product is new and because of the addition of a cryopreservation step, it was important that the consortium check if the bio-distribution will be changed by this additional step in the production process.
Actually, all the standard operating procedure for the clinical trial are in preparation (injection, immunomonitoring, randomisation, centralisation of the MRI, pharmaceutical circuit, monitoring plan…). We initiate the clinical trial with first inclusion planed end 2018.
Final results
Our primary goal is to validate a novel therapeutic approach for DDD, a major health and societal problem for which results of the conventional treatments are poor. Our proposal has solid basis that rest on previous research by the members of the consortium, which include not only basic research but also phase 2a clinical trials in DDD.
In this trial, we have the ambition to use freshly released allogeneic cells from a cGMP facility to the multiple clinical sides. This requires logistic steps that have been taken into account by consortium members. The cGMP manufacturing companies (Citospin) and Univercellbiosolution, through previously validated standard procedures in the shipment of cGMP produced cells for cellular therapeutic applications.
The secondary goal is to develop potency test predictive of efficacy, in order to anticipate future industrial development: Biomarkers to follow intradiscal MSC biological activity and assess the allogeneic immune response.
The final goal after validation of the cell product and clinical trial efficacy is to develop innovative therapies for large EU population and to be able to commercialize the product in the future. The consortium has extensive experience in manufacturing cell therapy products, which enables the identification of the main challenges in the industrialization of regenerative medicine. To address them, strong focus on pursuing new manufacturing strategies will be done for allogeneic cell production (Citospin, UniverCell Biosolution) already authorized by the Spanish Medicine Agency as well as French ANSM and authorized through recent VHP procedure. This approach will also contribute to reduce manufacturing costs. Production improvements will be faced through researching optimization of the production and transport protocols as well as cryopreservation. Participation of two SME that are pioneers in this area will help to deliver the new solutions to the market and to compete in optimal conditions. Throughout the project and with the support of our TTO’s representatives (WP1) we will be attentive to regularly review and take measures to protect the IP. In case the clinical results are encouraging RESPINE will develop this innovative medical product including quality controls, traceability and safety in order to be approved and reimbursed in the future on the EU market.
Website & more info
More info: http://www.chu-montpellier.fr/.