E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute open tibial shaft fractures |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10024956 |
E.1.2 | Term | Lower limb fractures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
Safety and tolerability of I-040202· Quality of life assessment and pharmacoeconomic evaluation To assess pharmacokinetics of PTH |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |