Long Bone Delayed-Union Fracture
Conditions
Keywords
Delayed-Union Fractures, Impaired Healing, Fractures, Orthopedics, Bone, Musculoskeletal Disorders
Brief summary
Fracture healing is a complex physiological process caused by interaction of cellular elements, cytokines and signaling proteins, which results in the formation of new bone. There is for now no universally accepted approach to evaluate the progression of fracture healing. Typically, a fracture is considered as a delayed-union when the bone has not united within a period of time that would be considered adequate for bone healing. Delayed-union suggests that union is slow but will eventually occur without additional surgical or non-surgical intervention, whereas non-union is defined as the cessation of all reparative process of healing. The incidence of impaired healing is estimated to range from 5 to 10% of all long bone fractures, depending on the fracture site, the type and degree of injury, among other factors. Currently the treatment of choice remains bone allograft or autograft. This procedure shows in general good results but requires an invasive surgery of several hours under general anesthesia, followed by a few days of hospitalization. Because of this, major complications have been reported in up to 20-30% of patients. The present Phase 1/2a study aims at demonstrating the safety and efficacy of ALLOB®, a proprietary population of allogeneic osteoblastic cells, in the treatment of delayed-union fractures of long bones. In this study, delayed-union is defined at the time of screening as an absence of healing of minimum 3 months and maximum 7 months (+/- 2 weeks) after the onset of the fracture.
Interventions
DRUGALLOB® implantation
Each patient will undergo a single administration of ALLOB® into the delayed-union site under anesthesia.
Sponsors
Bone Therapeutics S.A
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patient (or patient's legally acceptable representative) capable to provide a written, dated, and signed informed consent prior to any study related procedure * Non-infected delayed-union fracture of a long bone of minimum 3 months and maximum 7 months (+/- 2 weeks)
Exclusion criteria
* Fracture interline larger than 2.5 cm * Insufficient fracture stability * Multifocal fracture * Positive serology for hepatitis B, hepatitis C, Human Immunodeficiency Virus (HIV) * Current or past medical disease that could interfere with the evaluation of the safety and efficacy, as judged by the investigator * Severe renal or hepatic impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders at 6 Months (Efficacy of ALLOB) | 6 months | The success of the study will be based on the percentage of treated patients (ALLOB®) not failing under treatment. A patient will be considered as failed under treatment if, at Month 6: - He/she had a rescue surgery Or - The Global Disease Evaluation score (VAS) as perceived by the patient has not improved by at least 25% and the Tomographic Union Score (TUS) as assessed by CT scan has not increased by at least two points (versus baseline). |
Participant flow
Pre-assignment details
Of the 25 patients enrolled in the study (ICF signature), 22 patients were treated: * 2 patients were considered as non eligible before treatment * 1 patient withdrew consent before prior to Day 0
Participants by arm
| Arm | Count |
|---|---|
| ALLOB® Implantation One arm: ALLOB® Implantation
ALLOB® implantation: Each patient will undergo a single administration of ALLOB® into the delayed-union site under anesthesia. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | ALLOB® Implantation |
|---|---|
| Age, Continuous | 47.3 years STANDARD_DEVIATION 13.96 |
| BMI | 26.73 kg/m^2 STANDARD_DEVIATION 4.676 |
| Race/Ethnicity, Customized Caucasian/White | 22 Participants |
| Region of Enrollment Belgium | 13 participants |
| Region of Enrollment Germany | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 9 / 22 |
| serious Total, serious adverse events | 2 / 22 |
Outcome results
Primary
Percentage of Responders at 6 Months (Efficacy of ALLOB)
The success of the study will be based on the percentage of treated patients (ALLOB®) not failing under treatment. A patient will be considered as failed under treatment if, at Month 6: - He/she had a rescue surgery Or - The Global Disease Evaluation score (VAS) as perceived by the patient has not improved by at least 25% and the Tomographic Union Score (TUS) as assessed by CT scan has not increased by at least two points (versus baseline).
Time frame: 6 months
Population: The efficacy analysis was conducted on the Per Protocol population (21 treated patients; one patient being excluded from the analysis due on a major protocol deviation)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALLOB® Implantation | Percentage of Responders at 6 Months (Efficacy of ALLOB) | 100 percent of patients |
Comparison: The success of ALLOB® treatment was based on the percentage of responders. A treated patient was considered as responding if, at the end of the study (6 months):~* He/she had not required rescue surgery and~* The GDE score as perceived by the patient had improved by at least 25% or the TUS (tomographic union score) as assessed by CT scan had increased by at least 2 points.