Community Research and Development Information Service - CORDIS

H2020

ADIPOA2 Report Summary

Project ID: 643809
Funded under: H2020-EU.3.1.

Periodic Reporting for period 1 - ADIPOA2 (Clinical trial of autologous adipose-derived mesenchymal stromal cells (ASC) in the treatment of mild to moderate osteoarthritis)

Reporting period: 2015-01-01 to 2016-06-30

Summary of the context and overall objectives of the project

Osteoarthritis (OA) is a chronic and debilitating disease which occurs when the protective cartilage in the joints deteriorate sand breaks down. It can affect any joint in your body, but it most commonly occurs in the joints in your hands, knees, hips, and spine. Its symptoms include stiffness, pain, and swelling of the joint. Approximately 70 million Europeans are affected by the condition, and 25% of these individuals cannot perform the major activities of daily living. Treatment options include pain management with non-steroidal anti-inflammatories, corticosteroid injections, and joint replacement but there is currently no cure for OA.

ADIPOA-2 is developing and validating a revolutionary new stem cell treatment for OA. This therapy uses the patient's own stem cells. These cells are extracted from the patient's adipose (fatty) tissue and cultured under rigorous quality control in cell manufacturing facilities, before being injected into the patient's knee joint, where the stem cells help to reduce inflammation, and promote the repair of damaged cartilage. This treatment has already shown promise in an earlier clinical trial. Now ADIPOA2 is carrying out new research and conducting a larger clinical trial, which will move this treatment closer to the market and offer hope to the millions of Europeans who suffer from pain and debility as a result of OA. ADIPOA2 will also make an important contribution to the development of Europe's stem cell manufacturing infrastructure. This is vital if stem cell therapies are to become part of the therapeutic mainstream. ADIPOA2's research is making significant contributions in the following areas:

Developing cell production infrastructure:
The challenge of upscaling the production of high-quality stem cell products is one of the most significant barriers to the mainstream use of cellular therapies. ADIPOA2 is directly addressing this challenge by producing consistent batches of high-quality autologous (patient derived) stem cells under GMP (good manufacturing practice)- compliant conditions. The cells used in the ADIPOA2 trial will be produced in centres in France, Germany and Ireland. This ground-breaking multi-site approach will require cooperation between manufacturing centres and help to develop the production infrastructure that will allow for the wider use of stem cell therapies. ADIPOA2 is also contributing to European regulatory experience with stem cell products.

Mechanism of Action:
The ways in which stem cells control inflammation and promote tissue repair are still not fully understood. ADIPOA2 is conducting extensive research into the mechanism of action of these cells, helping to explain how they treat osteoarthritis, and how they may function in the treatment of other conditions. The project will use this knowledge to develop new assays and potency tests which will provide a affordable means to evaluate the clinical efficacy of stem cell treatments.

Clinical trial:
Building on the success of the earlier ADIPOA trial, ADIPOA-2 will carry out a Phase II randomised clinical trial of patient-derived stems cells in the treatment of advanced OA of the knee. This trial will involve the treatment of 150 patients across ten hospitals, located in France, Germany, Ireland, Italy, the Netherlands, and the United Kingdom. The trial will assess the safety and efficacy of the stem cell treatment, and will provide data for the validation and development of this treatment.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the first 18 months of the project we have made excellent progress towards achieving our objectives. We have laid the groundwork for the successful execution of our clinical trial and have successfully carried out experimental work on the mechanism of action of stem cells in the treatment of OA.

Our cell production partners have worked together to establish harmonise the production of ASC product for the clinical trial. They have harmonised production and shipping procedures to ensure the consistent production of the cell product required for the clinical trial. Validation runs have been performed in each of the production centres. BodyJet – a novel waterjet assisted liposuction technology – has been tested and validated as a safe and sterile means of obtaining adipose tissue from patients. All necessary preparation has been completed, and we are ready to start cell production for the clinical trial.

We have also carried out extensive regulatory interaction, including coordinating the legal requirements for conducting a clinical trial in the EU and addressing national requirements. The necessary documentation for regulatory applications have been completed and submitted. A Voluntary Harmonisation Procedure was initiated with the Paul Ehrlich Institute, the German national competent authority (NCA). As a result of this, national regulatory approval has successfully been obtained in a number of countries. Ethics applications to national authorities have also been prepared and submitted. As a result of this work, we are now in a position to begin the clinical trial.

The planning and design of the clinical trial has been a priority for the project in this period. The design of the ADIPOA2 trial has been finalised, and a clinical trial protocol has been produced. Standard operating procedures have been developed for all aspects of the trial to ensure consistency across the trial centres. Training in the use of the BodyJet equipment has been provided to the plastic surgeons involved at each centre. An electronic Case Report Form (eCRF) system has been put in place to manage clinical records from the trial. A Data and Safety Monitoring Board (DSMB) has been convened and has held its first meeting.

The project’s work on mechanism of action has involved a range of experiments in order to identify some of the relevant biological functions of ASC efficacy. These have achieved significant results, and experimentation is continuing. WP4 is also working to develop an assay that will allow the potency of stem cell products to be reliably and easily determined. The availability of this sort of assay is an important element in the mainstream clinical deployment of ASCs. A potential assay has been identified and validated to determine the immunosuppressive capacity of stem cell preparations. The results of this assay will be correlated with clinical findings as the clinical trial progresses.

We have also been actively engaged in disseminating the project. Online dissemination resources (a project website, social media profiles) have been created, and are being used to inform members of the public, researchers, and related projects about the work of ADIPOA2. Brochures and banners publicising the project have also been created.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Since the start of the project, ADIPOA2 partners have been actively promoting the projects in the media, institutional publications, and academic conferences.
We have maintained an active social media precence, and the project has been publicised in a range of media outlets.

One of the most significant impacts of ADIPOA2 is the development of the European stem cell production infrastructure. We have already made a significant contribution to this as the three cell production centres involved in the project have developed and validated standardised procedures for the production and shipping of cell therapy products.

Our work on a robust and affordable potency mechanism for ASCs will also provide a vital infrastructural element for the mainstream clinical use of stem cell therapies. Our experiments have laid the basis for the clinical validation of a promising assay.

In this period, we have laid the groundwork for the ADIPOA2 clinical trial. As we begin to analyse the results from this trial we will continue to achieve significant and transformative impacts.

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