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

Phase 1

Conditions: Acute open tibial shaft fractures
MedDRA version: 9.1Level: HLTClassification code 10024956Term: Lower limb fractures

Registration Number: EUCTR2006-005093-40-FR

Lead Sponsor: Kuros Biosurgery AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 200

Inclusion Criteria

1) patients with acute open fracture of the tibial shaft secondary to trauma assessed by medical examination and current radiographs indicated for open fracture reduction and internal fracture fixation with osteosynthesis plates or intra-medullary nail
2) soft tissue management (if medically warranted, e.g. debridement, irrigation) within 6 hrs after 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 prior to treatment start (at screening)
6) females of child-bearing potential must agree to have acceptable contraception for at least 3 months after receiving the study medication I-040202. Acceptable contraceptive measures are:
Hormonal types of birth control with a failure rate of less than 1% per year (such as implants, injections, combined oral contraceptives, patches or other methods) or copper IUDs or other IUDs with a failure rate of less than 1% per year, AND an additional barrier type of birth control measure (such as condoms, diaphragms, cervical caps,etc)
Sterilized women and abstinent women of child-bearing potential will not be required to take contraceptive measures.
7) willingness and ability to understand, participate and comply with the study requirements
8) signed Informed Consent Form. The patient has to be able to give consent personally.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) IIIc open fracture according to the Gustilo-Anderson classification
2) tibial defects requiring bone-grafting (e.g. large segmental defects)
3) duration from trauma to surgery longer than 14 days
4) concomitant acute bone injuries and/or major skin or other significant injuries that in the opinion of the investigator would interfere with the tibial shaft fracture healing process
5) concomitant ipsilateral tibial fractures other than in the diaphyseal region
6) evidence of immune suppression
7) suspected or known hypersensitivity to the study medication or components of it
8) evidence of hypercalcemia
9) hyperparathyroidism
10) on treatment and/or planned treatment with products containing PTH (e.g. Forteo)
11) pregnant or lactating females
12) participation in another clinical trial within the last 3 months
13) active or past history of malignant tumor
14) history or evidence for any hereditary or acquired chronic metabolic bone disease other than primary osteoporosis
15) history or evidence for any clinically relevant organ failure or any other relevant medical condition that, in the opinion of the investigator, will relevantly interfere with the assessment of study outcome or will impose hazard to the patient if study therapy will be initiated
16) known history of allergy to anaesthetics
17) evidence of moderate or severe renal failure (serum creatinine > 3.0 times ULN, NCI CTC grades 3 and 4
18) known history of allergic thrombocytopenia (type II) induced by heparin
19) inexplicable elevations of alkaline phosphatase >5.0 times ULN, NCI CTC grades 3 and 4
20) prior external beam or implant radiation therapy to the skeleton

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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;Secondary Objective: Safety and tolerability of I-040202·<br>Quality of life assessment and pharmacoeconomic evaluation<br>To assess pharmacokinetics of PTH;Primary end point(s): Proportion of patients healed 6 months after surgical treatment (T0) by clinical investigators' assessment:<br><br>Ø clinical criteria: weight bearing, reduced pain to manual stress and walking without aid and <br>Ø lack of need for surgical interventions to the fractured site with the intention of promoting bone healing (secondary intervention) and<br>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 Outcome Measures

Name	Time	Method

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