The primary aim of the ORTHOUNION clinical trial is to test the superiority of the Investigational Medicinal Product (IMP) versus Iliac Crest Autograft (ICAG) in long bone non-unions fractures in a multicentre, multinational, randomized trial. The main secondary objective is to test the non-inferiority of the two proposed doses of the IMP.
The standard of care of non-unions fractures is the ICAG. This autograft is a fragment of bone from the Iliac Crest (above the patient’s hip) to fill the non-union site under a surgical procedure.
Our research group developed an Investigational Medicinal Product (IMP) using expanded stem cells. There are several types of stem cells in the human body. These cells have high multiplication rate and can develop into different tissues. Based on these properties, multiple research projects developed the possibility to harvest these from humans, to grow these in cell cultures outside the human body and to use the resulting cell product as a therapy to reconstruct damaged organs or tissues. Mesenchymal stromal (stem) cells (MSC) are the cells that can develop into tissue binding cells, adipose tissue, cartilage tissue, bone tissue and other. MSCs can be found in particularly in bone marrow, but also in different body tissues, such as adipose tissue and other.
The ORTHOUNION IMP consists in autologous (patient’s own cells) MSCs cultured from Bone Marrow (BM-MSC) with the ability to repair tissue. This IMP will be combined with a commercial Biomaterial (MBCP+) to fill the non-union site under surgical procedure.
A recruitment of about 100 patients is planned from 20 clinical centres located in France, Germany, Italy and Spain. Study participants will be followed during two years after surgery or until bone healing. The IMP will be produced in 5 different production centres located in the mentioned countries.
Participants will be randomly assigned to either the ICAG arm, or the experimental low dose arm, or the experimental high dose arm, as is explained in the following table, with a 1:1:1 allocation (experimental high dose: experimental low dose: control).
(G1:Active comparator arm)
|Iliac Crest Autograft||About 10cc of spongious bone||Local administration under surgical procedure in non-unions after fractures|
|High-dose of BM-MSC+B
(G2a: Experimental arm)
|Expanded Bone Marrow Mesenchymal Stem Cells, plus Biomaterial (MBCP+®)||200×106 cells in 10cc of biomaterial|
|Low-dose of BM-MSC+B
(G2b: Experimental arm)
|100×106 cells in 10cc of biomaterial|
The European Clinical Research Infrastructure Network (ECRIN) and the Madrid Health Service (SERMAS) will be responsible of the regulatory aspects of the trial, and the Autonomous University of Madrid (AUM) will respond as Sponsor.
The ORTHOUNION clinical trial will be authorized by each Respective National Competent Authority and the Ethics Committees before starting with the recruitment. The study will be conducted in compliance with the protocol, regulatory requirements, good clinical practice (GCP) (E6_R1_Guideline.pdf) and the ethical principles of the Declaration of Helsinki (79(4)373.pdf) as adopted by the World Medical Assembly, 1996 (and subsequent revisions).