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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - MAXIBONE (Personalised maxillofacial bone regeneration)

Teaser

Summary

Bone is the most transplanted tissue with about 1 million procedures every year in Europe and there are a large number of European patients concerned by maxillofacial bone regeneration. However, there are only few early stage clinical studies with a limited number of patients that have proven safety of an alternative regenerative treatment consisting of stem cells with biomaterials. Therefore, there is a need to perform randomized late stage comparative clinical trial to demonstrate equivalent efficacy of stem cells and biomaterials as advanced therapy medicinal products in comparison to the current standard, autologous bone grafting. In view of the above, the objective of Maxibone are:
- To perform a comparative RCT for bone augmentation of the maxillary and mandible of patients prior to dental implants to asses the safety and effectiveness of the cell therapy and biomaterials to regenerate bone in width and height in order to enable adequate implant placement
- To evaluate clinical efficacy of bone regeneration on 150 patients by using Cone Beam Computed Tomography and histology analysis of core biopsies.
- To perform a health economic evaluation of autologous culture expanded BM-MSCs on bone regeneration versus the standard of care, autologous bone grafting.
- To decrease the production costs of the cell therapy products by using automated bioreactors
- To develop patient specific 3D printed biomaterial scaffolds

Work performed

In the first reporting period of the project, the partners have attended a kick off meeting and a training session for surgeons on human subjects organised in Nantes in February 2018. The partners have collaborated to prepare the clinical files for submission to the regulatory agencies and ethical committees. The clinical protocol, investigational brochure, investigational medicinal product dossier, informed consent, case record form, medical insurance have been finalised and submitted to the medical agencies by the sponsor through a voluntary harmonisation procedure in November 2018. The clinical files have however been rejected by the medicinal agencies in April 2019 and the revised files re-submitted in July 2019. The partners have collaborated to design and test a customised electronic CRF for recording patients data. Clinicians have identified patients and performed bone marrow aspirations with haematologists and orthopaedic surgeons. A dedicated website www.maxibone.eu has been launched for dissemination purposes.

Cell manufacturing partners (EFS, UULM) have continued to improve and to standardise the manufacturing process. They have tested automated bioreactors in order to decrease production costs.

In order to personalise biomaterials, medical images of large animals have been converted to printable files by INSERM and 3D scaffolds fitting the anatomy have been produced by the spin off company MIMETIS. These 3D scaffolds together with human stem cells have been tested in vitro and in vivo.

The partners have gathered in the General Assembly meeting in Bergen in February 2019.

Final results

MEDICAL AND SOCIAL IMPACTS
This clinical study will directly impact a large number of patients by developing new strategies for regenerative medicine and therapeutic intervention. The Maxibone project will be focused on vertical bone defects in the jaw. Maxibone is an innovative bone defects reconstruction alternative expected to show an equivalency or a superiority compared to the current gold standard, autologous bone grafting. In parallel of the clinical trial, MAXIBONE consortium will also perform pre-clinical studies with a novel patient specific 3D printed synthetic bone substitute combined with autologous MSC for large defects of the mandible and maxillary bone in minipigs.
By performing the late stage clinical and preclinical studies, MAXIBONE wishes to improve the offer in maxillofacial bone reconstruction, both ensuring a solution that would be able to quickly reach the patients and respond to the clinical need.

ECONOMIC IMPACT
The bone disease market is one of the largest heathcare markets worldwide. In the bone reconstruction segment, in Europe and in the USA there are annually over 4 million procedures requiring bone graft. Developing projects such as Maxibone could help answer current issues Europe is facing and more specifically concerning the relations between academia and industry. The two indutrial partners that will collaborate in the project are Straumann and Mimetis and some others as a third party. The implication of these companies reflects the interest of the European market in cell therapy for bone regeneration and will help to lever existing investments in fundamental research into regenerative medicine and more specifically in the maxillofacial area.
In Europe around 4 million dental implants are performed per year but in 10% of the cases there is not enough bone to place the implant. In these cases, autologous bone grafting is required but it could be replaced in the next years by bone regeneration using cell therapy and biomaterials.