E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Closed Fractures of the Humerus |
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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 | 10017127 |
E.1.2 | Term | Fracture of humerus |
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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 |
Demonstrate that fracture union is accelerated in subjects with humeral fractures (proximal, shaft) treated with conservative (nonoperative) therapy SOC and a single dose of rhBMP-2/CPM (either 1.0 or 2.0 mg/mL) compared to subjects who are treated with SOC alone |
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E.2.2 | Secondary objectives of the trial |
1. Demonstrate the safety of administering rhBMP-2/CPM in subjects with closed humeral fractures including key safety outcomes. 2. Demonstrate feasibility by establishing a satisfactory method of administering rhBMP-2/CPM to implement in a phase 3 efficacy trial for this clinical indication |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects signed and dated IRB or IEC-approved informed consent form. 2. Skeletally mature and aged >= 18 years (closed epiphysis). 3. Subjects with a either a closed proximal humeral fracture or a diaphyseal humerus fracture classified as: - Proximal Humeral Fracture (NEER classification): nondisplaced, minimally displaced (<45° angluation and <1cm displaced), 2-Part, 3-Part or 4-Part - Diaphyseal Humeral Fracture (OTA classification): Simple OTA 12-A- Wedge OTA 12-B or Complexe OTA 12-C 4. Treatment plan includes only conservative (non-operative) therapy within 48 hours of injury. |
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E.4 | Principal exclusion criteria |
1. Open proximal or humeral shaft fractures. 2. Additional planned procedure(s) to stimulate fracture union following application of an initial immobilization device. 3. Shoulder dislocation at the time of injury. 4. Fractures located in the distal third of the humerus. 5. Concurrent fractures of the ipsilateral or contralateral upper extremity that would impede performance on a functional assessment. 6. Neurovascular impairment in the region under study. 7. Documented history of heterotopic ossification. 8. Documented active infection in any anatomical location. 9. Retained surgical hardware in the humerus under study due to previous fracture. 10. Pathological fractures, except if due to postmenopausal or senile osteoporosis. 11. Treatment initiated for osteoporosis within the past 16 weeks. 12. Any previous use of therapies that can be considered bone anabolic (parathyroid hormone, growth hormone, anabolic steroids or fluoride at bone therapeutic doses) within the past year. 13. History of other metabolic bone disorders that may affect the region under study (eg, Paget's disease, renal osteodystrophy, or benign tumor). 14. Documented history of malignancy, except basal or squamous cell carcinoma that has been treated and has fully resolved for a minimum of 5 years. 15. History of hypersensivity to rhBMP-2 or to protein pharmaceuticals (such as monoclonal antibodies or gamma globulins). 16. Treatment with any investigational therapy within the past 30 days. 17. Documented history of ongoing alcohol or drug addiction. 18. Any other concurrent condition(s) that, in the judgement of the investigator, would prohibit the subject from participating in the study or hinder the collection of data and interpretation of results (eg, unstable medical condition, life expectancy less than 1 year or inability to comply with required follow-up evaluations).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable in this study is radiographic union. Radiographic fracture union was selected as a surrogate endpoint for this study because it is considered a strong predictor of fracture healing |
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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) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |