Prospective Study in Adults Evaluating Safety & Efficacy of NVD003 for Bone Reconstruction to Treat Lower Limb Nonunion

Exclusion Criteria

• •1. The subject has a Body Mass Index (BMI) ≤ 20 kg/m² or ≥ 40 kg/m², or of ≥35 kg/m² with obesity-related health conditions, such as high blood pressure or diabetes.
• •2. Multifocal or comminuted fractures.
• •3. A planned use of an external fixator is not allowed as of the grafting surgery (V1) until V7.
• •4. Documented osteoporosis: bone density determined using DEXA scan on lumbar spine and hip: bone mineral density T-scores of -2.5 and below. An examination ≤ 1-year-old before screening is acceptable.
• •5. Pregnant or breast-feeding woman.
• •6. The subject shows signs of an active drug or alcohol dependence, serious current illness, mental illness or any other factors which, in the opinion of the investigator, will interfere with study conduct or the interpretation of the results.
• •7. The patient has a history of solid organ transplant at any point in the past or is on the waiting list for future organ transplantation.
• •8. The subject previously received a cellular therapy treatment at any point in time (as per protocol description).
• •9. Previous exposure to any experimental therapy with another investigational drug within 60 days prior to screening or enrolment in any concurrent study that may confound the results of this study.
• •10. Any signs or suspicion of an active local (area of the future surgical site), or systemic infection before the induced membrane surgery or the grafting surgery.
• •11. Known allergy to any antibiotics commonly used to treat Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus) or coagulase-negative staphylococci.
• •12. Diagnosis of HIV, HBV (HBsAg or PCR positive), HCV, Human T-cell Lymphotropic Virus (HTLV) 1 or 2, or syphilis infection (as confirmed by serology and nucleic acid test (NAT) by Tissue Establishment).
• •13. Chronic use of immunosuppressive therapy (immunosuppressant/ immunotherapy) due to inflammatory or systemic disease.
• •14. Any clinically relevant chronic disease associated with renal or hepatic insufficiency or any chronic disease of such severity that surgery could be detrimental to the survival of the patient.
• •15. Subjects with poorly controlled diabetes mellitus type 2 as assessed by glycated haemoglobin (HbA1C) ≥ 10%.
• •16. Subjects with poorly controlled thyroid diseases (unstable despite proper medication).
• •17. Subjects with documented metabolic bone disease (based on the investigator judgment) such as, but not limited to, osteogenesis imperfecta or osteomalacia.
• •18. Chronic, current or planned during study use of any medications that might affect bone metabolism or the quality of bone formation such as, but not limited to, bisphosphonates, steroids, methotrexate, anticoagulant therapies, immunosuppressant therapy or immunotherapy. However, short lasting surgery-related prophylactic treatments such as antibiotics, analgesics and low molecular heparin drugs may be administered according to hospital recommendations.
• •19. Existing malignant tumour in the vicinity of the graft or a resected one not cured for more than 5 years.
• •20. Any other illness which might reduce life expectancy to less than 2 years from screening.
• •21. The subject is a prisoner.