Non-infected delayed-union fractures MedDRA version: 20.0 Level: PT Classification code 10017081 Term: Fracture delayed union System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Bone Therapeutics S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient aged 18 to 80 years inclusive - Patient diagnosed with a non-infected delayed-union fracture of a long bone (femur, tibia, fibula, humerus, ulna, radius) of minimum 3 months and maximum 7 months (± 2 weeks) without signs of healing over the last 4 weeks at the time of screening - Modified Radiographic Union Score (mRUS)* =65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: Current symptoms and/or signs related to the disease under study - Fracture interline > 2.5 cm, as defined by the Independent Radiologist - Insufficient reduction of the fracture - Insufficient fracture stability defined as osteolysis at the level of the nails/screws and/or defect and/or mobility of the osteosynthesis material at physical examination, as assessed by the Investigator - Osteosynthesis material revision or surgery (i) performed less than 2 months from the screening visit at the fracture site or (ii) performed less than 4 weeks from the screening visit at distance of the fracture site. - Active bone infection (at site) - Femoral neck fracture, if the femur is the target bone of the study - Multifocal fracture (e.g., more than one fracture site on the studied bone) - Symptomatic delayed/non-union fracture on the neighbouring bone , as judged by the Investigator - Severe nerve damage and/or neuropathic/neuropathic-like pain at fracture site, that may interfere with assessment during the study, as appreciated by the Investigator - Severe tendon lesion (e.g., rupture or enthesopathy) at fracture site, that may interfere with assessment during the study, as appreciated by the Investigator Current or previous diagnoses, signs and/or symptoms - Positive serology for HIV (defined as positive Anti-HIV 1 and/or 2 and/or positive PCR) - Active hepatitis B (defined as positive HBs Ag and/or positive PCR) - Active hepatitis C (defined as positive Anti-HCV and/or positive PCR) - Global sepsis - Renal impairment, defined as serum creatinine >2 mg/dl or 176 µmol/L - Hepatic impairment, defined as alanine aminotransferase or aspartate aminotransferase = 3 times the upper normal limit - Poorly controlled diabetes mellitus (defined as HbA1C >8%) - Known allergy to gentamicin - History of hypersensitivity to human biological material including blood and blood derived products, documented clinically or by laboratory tests - Current or past history of solid or haematological neoplasia - History of organ or bone marrow transplantation - Active autoimmune disease (e.g., sclerodermia, Sjögren syndrome, lupus,...) - Any concomitant disease that could interfere with the evaluation of efficacy, as judged by the Investigator, including but not limited to local or metabolic bone diseases - Life expectancy less than 6 months Current or previous treatment - Patients who have previously been treated with ALLOB® - Participation in another clinical study involving a pharmacological treatment within 3 months prior to screening - Current (or within 1 month of screening) treatment with calcitonin, raloxifen, teriparatide, and/or strontium ralenate - Current (or within 6 months of screening) illicit drug abuse (as per local law) Safety aspects concerning female subjects of childbearing potential - Pregnancy - Breast-feeding - Woman not willing or able to use a reliable contraceptive method for at least 6 weeks prior to screening and during the whole study period. Reliable contraceptive methods include orally administered hormonal contraceptives, surgical intervention (e.g., tubal ligation), and intrauterine device (IUD). - Woman with positive urine pregnancy tests at Visits #1 and/or #2. Other exclusion criteria - Body Mass Index (BMI) of 35 kg/m2 or greater - Unable to undergo general anaesthesia or a surgical intervention
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the main study is to assess the safety and efficacy of ALLOB® single percutaneous implantation in healing delayed-union fractures at the end of the study period (Month 6). Safety: Subjects will be systematically assessed for the potential occurrence of any AE or SAE, related to the product or related to the procedure, using patient open questionnaires, physical examination, (including vital signs), and laboratory measurements. Efficacy: The success will be based on the percentage of treated patients (ALLOB®) not failing under treatment. A patient will be considered as failed under a treatment if, at the end of the study period (Month 6), the patient had required a rescue surgery or the Global Disease Evaluation score (VAS) as perceived by the patient has not improved by at least 25% and the TUS as assessed by CT scan has not increased by at least two points (versus baseline).;Secondary Objective: The efficacy of ALLOB® will also be evaluated on other efficacy parameters: - Global Disease Evaluation as perceived by the Investigator (at 6 Months and over time) and by the patient (over time) using a Visual Analogue Scale - Pain using a visual analogue scale (at rest, during activities and at palpation) (at 6 Months and over time) - Weight-bearing using a Likert Scale (at 6 Months and over time) - Radiological improvement using the TUS as assessed by CT scan over time - Radiological improvement using the mRUS as assessed by X-ray (at 6 Months and over time) - Biodistribution of ALLOB® - Evolution of bone metabolism - Variations in the biomarkers - Radiological improvement of untreated fractured neigbouring bone using TUS and/or mRUS as assesssed by CT scan and X-ray, respectively;Primary end point(s): Safety Criteria : In addition to standard pharmacovigilance requirements, particular attention will be given to AE suggesting immune-mediated reactions, such as: general discomfort, uneasiness, ill feeling, pain or swelling in the | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Other efficacy endpoints: - Evolution from baseline to each time point of the Global Disease Evaluation score (VAS) as perceived by the patient and physician - Evolution from baseline to each time point of the TUS score as assessed by CT scan - Evolution from baseline to each time point of Pain VAS at rest, during activities and at palpation (as performed by the physician) as assessed by the patient - Evolution from baseline to each time point of Weight-Bearing score - Evolution from baseline to each time point mRUS score assessed by conventional X-ray - Evolution from baseline to each time point of the biodistribution of the ALLOB® cells - Evolution from baseline to each time point of the bone metabolism - Evolution from baseline to each time point of the biomarkers - Evolution from baseline to each time point of the TUS and/or mRUS score(s) of untreated fractured neighbouring bones (e.g., fibula left untreated when the tibia is the target bone of the study) as assessed by CT scan and/or X-ray;Timepoint(s) of evaluation of this end point: Efficacy endpoints will be determined at each scheduled visit over the 6-month follow-up period (at 2 weeks, 1, 3 and 6 months). | — |
Countries
Belgium, Germany, United Kingdom
Contacts
Public ContactClinical Trial Information
Bone Therapeutics S.A.
Outcome results
None listed