A phase II randomized, controlled, open-labeled (dose-blinded) dose finding study of the safety and efficacy of I-040202 in the treatment of patients with acute open tibial shaft fractures - N/A

INTERVENTION: Product Name: Osteogenic Paste Product Code: I‐040202 Pharmaceutical Form: Implant Current Sponsor code: Kuros PTH1‐34 Other descriptive name: TGplPTH1‐34 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 0.133‐ Product Name: Osteogenic Paste Product Code: I‐040202 Pharmaceutical Form: Implant Current Sponsor code: Kuros PTH1‐34 Other descriptive name: TGplPTH1‐34 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 0.4‐ Product Name: Osteogenic Paste Product Code: I‐040202 Pharmaceutical Form: Implant Current Sponsor code: Kuros PTH1‐34 Other descriptive name: TGplPTH1‐34 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 1.0‐ CONDITION: Acute open tibial shaft fractures ; MedDRA version: 9.1 Level: HLT Classification code 10024956 Term: Lower limb fractures PRIMARY OUTCOME: Main Objective: To assess and compare the proportion of patients healed 6 months after surgical management of acute open tibial shaft fracture using standard of care (SoC) versus SoC plus a single application of I‐040202 Primary end point(s): Proportion of patients healed 6 months after surgical treatment (T0) by clinical investigators' assessment:; ; Ø clinical criteria: weight bearing, reduced pain to manual stress and walking without aid and ; Ø lack of need for surgical interventions to the fractured site with the intention of promoting bone healing (secondary intervention) and; Ø radiographic criteria: cortical bridging (periosteal and/or endosteal), disintegration and disappearance of fracture lines and absence of signs for complications such as infection or mal‐union Secondary Objective: Safety and tolerability of I‐040202· ; Quality of life assessment ; To assess pharmacokinetics of PTH INCLUSION CRITERIA: 1) patients with an acute open fracture of the tibial shaft secondary to trauma assessed by medical examination and current radiographs indicated for open fracture reduction and internal fixation using osteosynthesis plates or intra‐medullary nails 2) soft tissue management (if medically warranted, eg. debridement, irrigation, application of antibiotics) performed according to local hospital practice no later than 24h after the trauma 3) male and female patients = 18 years 4) body mass index (BMI) 16‐33 (minimum body weight 50 kg, maximum 140 kg) 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 the study medication. Acceptable contraceptive measures are: ‐ Hormonal types of birth control with a failure rate