Patients with documented recalcitrant lower limb nonunion, meaning a single, meta- and/or diaphyseal nonunion defect of femur or tibia after at least one failed reconstructive surgical attempt.
Conditions
Sponsors
Novadip Biosciences
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female adult subject (=18 years). - Radiographic images not older than 3 months, confirming lower limb nonunion, defined as the absence of clinical and radiographic progression towards healing aver 3 consecutive months on serial radiographs and minimum 9 months after the first attempt of surgical bone repair, or minimum 6 months after the second (or any subsequent) attempt of surgical bone repair. - Radiologic single, meta- and/or diaphyseal bone defect with a maximum size of 4 cm (in case of a void that does not transverse the whole width of the bone, the total volume cannot exceed the volume corresponding to the 4 cm gap). - The impaired limb is salvageable and the patient is eligible for the intended surgical procedure according to the standard hospital practice. - Documented normal or low bone density: Bone density scan determined by Dual Energy X-Ray Absorptiometry DEXA scan on lumbar spine and hip (bone mineral density T-scores above -2.5). An examination = 1 year-old before screening is acceptable. - The subject is, in the Investigator’s opinion, psychosocially, mentally and physically able to fully comply with this protocol, including the postoperative regimen and follow-up visits. - Use of an effective birth control method for 2 months prior to the date of the intended surgical intervention up to Visit V7 for women of childbearing potential. - Negative urinary pregnancy test for women of childbearing potential. - Safety laboratory test results and serology at screening are medically acceptable to undergo surgery. - Serology panel for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and syphilis must be negative at screening. - The subject has understood the nature of the study, agrees to its provisions, and has accepted to participate in the study and to follow all study procedures. This is acknowledged by signing the informed consent as approved by the required Institutional Review Board/Ethics Committee and the national competent authorities. - Patient fulfils the criteria to donate his human body material (adipose tissue) and is suitable to undergo a liposuction. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: - 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. - Multifocal or comminuted fractures. - A planned use of an external fixator is not allowed as of the grafting surgery (V1) until V7. - 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. - Pregnant or breast-feeding woman. - 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. - 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. - The subject previously received a cellular therapy treatment at any point in time (as per protocol description). - 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. - 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. - Known allergy to any antibiotics commonly used to treat Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus) or coagulase-negative staphylococci. - Diagnosis of HIV, HBV, 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). - Chronic use of immunosuppressive therapy (immunosuppressant/ immunotherapy) due to inflammatory or systemic disease. - 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. - Subjects with poorly controlled diabetes mellitus type 2 as assessed by glycated haemoglobin (HbA1C) = 10%. - Subjects with poorly controlled thyroid diseases (unstable despite proper medication). - Subjects with documented metabolic bone disease (based on the investigator judgment) such as, but not limited to osteogenesis imperfecta or osteomalacia. - 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. - Any other illness which might reduce life expectancy to less than 2 years from screening. - The subject is a prisoner.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety of the use of NVD-003 in patients with recalcitrant lower limb nonunion. ;Secondary Objective: To assess the healing efficacy of NVD-003 by radiographic assessments. To assess the healing efficacy of NVD-003 by clinical assessments. To assess patient reported outcomes such as pain (pain severity and pain interference with function), quality of life and overall treatment effect. To assess the local complication rate after graft implantation (i.e. revision, removal, reoperation, supplemental fixation). To assess long-term safety of NVD-003. ;Primary end point(s): - All AEs including Serious Adverse Events (SAEs). - Adverse Events of Special Interest (AESI) and Procedure Related AEs (PRAE). - Vital signs abnormalities. - Physical examinations abnormalities. - Safety laboratories abnormalities. ;Timepoint(s) of evaluation of this end point: All AEs (including SAEs), AESI and PRAEs: From graft implantation until completion of visit V7. The study duration per patient will not exceed 24 months post-implantation. Vital signs abnormalities, physical examinations abnormalities and safety laboratories abnormalities: at V2, 3, 4, 5, 6 and V7. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: - Healing efficacy (After graft implantation (V1) until visit V7). - Grafting surgery parameters (During implantation surgery and during hospitalization when implantation occurs). - Complications (12 and 24 months post-implantation surgery). - Quality of Life (at screening and at 6 weeks, 3 months, 6 months, 12 months and 24 months post-graft). - General safety reporting (from screening to pre-graft implantation). - Extended safety follow-up (all SAEs): between 24 months follow-up visit and 5 years post grafting surgery.;Secondary end point(s): - Healing efficacy - Grafting surgery parameters - Complications - Quality of Life - General pre-graft implantation safety - Long-term safety | — |
Countries
Belgium, Luxembourg
Contacts
Public ContactChief Medical Officer
Novadip Biosciences
Outcome results
None listed