E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Closed diaphyseal tibial fracture |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10043827 |
E.1.2 | Term | Tibia fracture |
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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 |
1. To demonstrate a reduction of time to fracture union based on assessments of radiographs by a central evaluation committee (CEC). 2. To demonstrate acceleration of return to normal function based on the time to full weight bearing (FWB) without pain at the fracture site, as established by the investigator. |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate safety of rhBMP-2/CPM administration including key safety outcomes. 2. To demonstrate earlier return to function with the Short Musculoskeletal Function Assessment (SMFA). 3. Assess feasibility of rhBMP-2/CPM administration |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject’s signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form before any protocol-specific screening procedures are performed. 2. Closed diaphyseal tibial fracture, Orthopaedic Trauma Association (OTA) classification 42A, 42B, or 42C. 3. Age > or =18 years and skeletally mature. 4. Closed reduction and definitive internal fracture fixation by means of a reamed, locked intramedullary (IM) nail within 72 hours after injury (SOC for the purpose of this study is defined as meeting these criteria). |
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E.4 | Principal exclusion criteria |
1. Concurrent fractures of the ipsilateral or contralateral lower extremity other than the ipsilateral fibula, that would impede performance on the functional assessment of full weight bearing (FWB). 2. Planned procedure(s) that stimulate fracture healing after IM nailing. 3. Impending compartment syndrome before randomization. 4. Pathological fractures, except if due to postmenopausal or senile osteoporosis. 5. History of other metabolic bone disorders that may affect the region under study (eg, Paget’s disease, renal osteodystrophy, or benign tumor). 6. Documented history of malignancy, except basal or squamous cell carcinoma. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variables for the trial stem from radiographic, and functional assessments aimed at evaluating the key fracture outcomes of fracture union and restoration of functional mobility. Fracture union is the first co-primary endpoint. It will be determined from radiographic assessments by a CEC masked to treatment assignment. Fracture union is defined as the presence of callus bridging the fracture line(s) and/or obliteration (disappearance) of the fracture line(s) visualized on at least 3 of 4 diaphyseal aspects on orthogonal radiographic views. Bridging callus is defined as the appearance of mineralized callus, spanning the proximal and distal fracture fragments. Bridging callus should be sufficiently mineralized such that it remains visible on follow-up radiographs, without regression, thereby supporting the diagnosis of “fracture union”. Obliteration (disappearance) of the fracture lines refers to endosteal bone remodeling and should not be mistaken with obliteration by non-bony substances (eg, CPM). The second co-primary endpoint is subject’s ability to bear pain free full body weight on the affected limb. This indicates the subject’s ability to use the fractured limb for its normal function. The investigator will establish this endpoint. The secondary efficacy variable is the postoperative return to normal function assessed by means of a self-administered or interviewer-administered Short Musculoskeletal Function Assessment (SMFA). This 46-item questionnaire includes a function and bother index. Lower scores (on a scale of 0 to 100) are associated with a better health status. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 20 |
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 | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |