Fractures of the tibial plateau requiring grafting MedDRA version: 13.1 Level: HLT Classification code 10024956 Term: Lower limb fractures System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: TGplPTH1-34 in fibrin supplemented with hydroxyapatite/beta tricalcium phosphate granules
Product Code: I-0401
Pharmaceutical Form: Implant
Current Sponsor code: Kuros PTH1-34
Other desc
Sponsors
Kuros Biosurgery AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Radiological evidence of fracture of the tibial plateau requiring grafting and fixation that occurs either alone or is part of a polytraumatic event (AO classification: 41B2, 41B3, 41C2, 41C3). 2. Female and male subjects = 18 years. 3. Body mass index (BMI) 16-33 (minimum body weight 50 kg, maximum 140 kg). 4. Glasgow coma score (GCS) = 13. 5. Females of child-bearing potential must be willing to undergo a pregnancy test (urine) prior to treatment start (at screening). 6. Females of child-bearing potential randomized in the intervention group must agree to have acceptable contraception for at least 3 months after receiving I-0401. 7. Subjects must be able and willing to come to the clinic for follow up visits as scheduled in the time and events schedule. 8. Signed Informed Consent Form (ICF). The patient has to be able to give consent personally. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 152 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 31
Exclusion criteria
Exclusion criteria: 1. Total size of defect requiring a graft volume of > 7.0 mL. 2. Patients with high risk of amputation. 3. Open tibial plateau fractures Gustilo-Anderson grade III. 4. Concomitant ipsilateral fractures of the limb other than the fracture of the tibial plateau. 5. Active or past history of malignant tumor. 6. Evidence of systemic or localized infection at time of surgery. 7. Pregnant or lactating females. 8. Evidence of immune-suppression. 9. On treatment and/or planned treatment with products containing PTH (e.g. Forteo®, Forsteo®). 10. Evidence of hypercalcemia (serum calcium above ULN). 11. Known history of allergy to anesthetics. 12. Suspected or known allergies towards any of the components of I-0401 (TGplPTH1-34, Fibrin, HA/TCP granules). 13. History or evidence for a metabolic bone disease other than primary osteoporosis. 14. Known clinically significant organ or systemic diseases or any other relevant medical condition such that in the opinion of the investigator, the significance of the disease or condition will impose hazard to the patient if study therapy will be initiated or will compromise the subject’s participation in the study. 15. Participation in another clinical trial within 3 months prior to trial start. 16. Evidence of moderate or severe renal failure (serum creatinine > 3.0 times ULN, NCI CTC grades 3 and 4). 17. History of allergic thrombocytopenia (type II) induced by heparin. 18. Inexplicable elevations of alkaline phosphatase (alkaline phosphatase > 5.0 times ULN, NCI CTC grades 3 and 4). 19. Prior external beam or implant radiation therapy to the skeleton.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effects of a single implant of I-0401 (2 different concentrations) given in addition to internal fixation in tibia plateau fractures requiring grafting;Secondary Objective: - To assess the tolerability and safety of I-0401 - To assess pharmacokinetics of PTH - To assess quality of life and pharmacoeconomics;Primary end point(s): The proportion of patients with radiological fracture union at 16 weeks after implantation of the graft. Assessments will be performed by an independent radiological panel and will be based on CTs. Radiological fracture union will be defined using the following criteria: - Cortical bridging on at least 1 visible cortical plane and - Obliteration of fracture lines and - Dislocation of bone fragments compared to the post-operative film. ;Timepoint(s) of evaluation of this end point: 16 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Loss of reduction of the tibia plateau (in mm) at 6, 12, 16, 26, 52 and 104 weeks after surgery compared to the post-operative assessment as measured by an independent radiological panel. • The proportion of patients with radiological fracture union at 52 and 104 weeks as assessed by an independent radiological panel. • Proportion of patients with fracture healing at 16 weeks after implantation of the graft as assessed by the investigators considering clinical and radiological criteria. Clinical assessment will consider the level of pain upon weight bearing on fracture site, the level of redness/swelling of the knee and whether a secondary intervention was necessary to promote fracture healing. Radiological criteria will consider cortical bridging and fracture lines. • Time to fracture healing as assessed by the investigators considering clinical and radiological criteria (see above for fracture healing assessment). • The number of secondary interventions due to non-healing within 52 weeks and within 104 weeks from time of surgery comprises: o All surgical procedures to promote fracture-healing. o All surgical procedures to perform a knee arthroplasty o Non-invasive treatments (e.g. ultrasound) to promote fracture-healing.;Timepoint(s) of evaluation of this end point: • Loss of reduction of the tibia plateau (in mm) at 6, 12, 16, 26, 52 and 104 weeks after surgery • The proportion of patients with radiological fracture union at 52 and 104 weeks • Proportion of patients with fracture healing at 16 weeks after implantation of the graft as assessed by the investigators considering clinical and radiological criteria. • Time to fracture healing as assessed by the investigators • The number of secondary interventions due to non-healing within 52 weeks and within 104 weeks from time of surgery comprises: oAll surgical procedures to promote fracture-healing. oAll surgical procedures to perform a knee arthroplasty oNon- | — |
Countries
Australia, Canada, France, Germany, Hungary, Italy, Poland, Spain, Switzerland, United Kingdom
Contacts
Public ContactChief Medical Officer
Kuros Biosurgery AG
Outcome results
None listed