Efficacy of Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells and Biomaterial in Delayed Union and Non-Union Long Bone Fractures

The primary objective of this study is to evaluate the efficacy of a combined advanced therapy medicinal product (ATMP) consisting of allogeneic bone marrow-derived mesenchymal stromal cells and a biomaterial for achieving radiological consolidation in patients with delayed union or non-union of long bone fractures. Success is defined as a consolidation rate exceeding 90% at 12 months post-surgery. Secondary objectives include:

• Assessment of radiological consolidation at 6 months post-surgery.
• Evaluation of bone healing using the Reborne scale at 6 and 12 months.
• Measurement of pain at the fracture site, both with and without weight bearing, at 6 and 12 months.
• Determination of reoperation frequency at 6 and 12 months.
• Analysis of the clinical and radiological bone consolidation ratio at 6 and 12 months.
• Quantification of regenerated bone volume via computed tomography (CT) at preoperative, 6, and 12 months.
• Monitoring the clinical safety of the investigational medicinal product (IMP) for up to 2 years.

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients within the specified age ranges. Participants are required to have a diagnosis of a traumatic isolated closed or open Gustilo classification I, II, IIIA, or IIIIB humerus, tibial, or femur diaphyseal or metaphysodiaphyseal fracture. Inclusion requires the presence of either delayed union, characterized by an absence of bone bridging and a visible fracture line between four and nine months after the acute injury, or non-union, defined by insufficient bone bridging, insufficient biological activity, and the failure of previous treatments at least nine months after the trauma. Eligible individuals must be at least 18 years of age at the baseline visit.

This single-arm, multi-centre study is designed to evaluate the efficacy of a combined advanced therapy medicinal product consisting of allogeneic bone marrow-derived mesenchymal stromal cells and a biomaterial for the treatment of delayed union or non-union following long bone fractures. The research methodology involves an intraosseous administration of a suspension for injection. Following the screening visit to confirm eligibility based on age and fracture characteristics, participants undergo surgical intervention. The protocol includes follow-up visits requiring computed tomography at 6 and 12 months post-surgery to assess radiological consolidation. The primary objective is to determine the percentage of patients achieving bone healing at 12 months. Secondary endpoints include the assessment of pain scores using the Numeric Rating Scale, the Reborne scale, volumetric bone regeneration, and the rate of reoperation. Safety is monitored through the early complication rate within the first 3 months and the overall complication rate. The total duration of participant involvement extends to 12 months post-intervention.

The experimental treatment consists of ORTHOALLO-BM-MSC, which is an allogeneic bone marrow-derived mesenchymal stromal cells product obtained from selected donors. This substance is provided as a suspension for injection and is administered via an intraosseous route at a dose of 220,000,000 units.

The therapeutic approach involves the combination of the experimental cells with a biomaterial to facilitate bone healing in cases of delayed union or non-union following long bone fractures.

The primary efficacy endpoint is the percentage of patients achieving radiological consolidation at 12 months following the intervention. Secondary efficacy parameters include the percentage of patients with radiological bone consolidation at 6 months and the assessment of the Reborne scale at 6 and 12 months.

Pain assessment is conducted using the Numeric Rating Score (NRS) on a scale from 0 to 10, measured at preoperative stages and at 6 and 12 months after surgery, both with and without weight bearing. The rate of reoperation at the callus site is evaluated at 6 and 12 months. The percentage of patients experiencing bone consolidation is also recorded at 6 and 12 months. Volumetric assessment of the regenerated bone is performed as a percentage of 10cm3 of the affected long bone, utilizing Region of Interest methodology via Osirix® software applied to full CT images at preoperative, 6, and 12 months post-surgery.