E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acceleration of fracture healing |
|
MedDRA Classification |
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 investigate the effect of AMG 785 compared to placebo on functional healing as measured by the timed-up-and-go test (TUG) over Weeks 6 through 20 in subjects with fresh unilateral low energy intertrochanteric fracture of the proximal femur. |
|
E.2.2 | Secondary objectives of the trial |
To investigate the effect of AMG 785 compared to placebo on:
• TUG by visit • Time to radiographic healing • Harris Hip Score • Pain as a result of the hip fracture as assessed by the Visual Analog Scale (VAS) |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Dual energy X-ray Absorptiometry (DXA) and PK/PD sub-study, version dated 22 October 2009: Approximately 40 subjects per arm (approximately 160 subjects in total) will be enrolled into this sub-study to undergo DXA scans of the lumbar spine and proximal femur and have blood drawn for PK/PD analysis. This sub-study will evaluate the percent change from baseline on lumbar spine and hip BMD at Week 52. Blood samples will be used for assessment of AMG 785, sclerostin, and bone turnover markers P1NP and CTX. |
|
E.3 | Principal inclusion criteria |
Adult women or men, age ≥ 55 to ≤ 90 years at randomization
Fresh unilateral low energy intertrochanteric fracture of the proximal femur as the primary injury, confirmed by X-ray
Fractures eligible for this study must have one of the following characteristics • At least three fragments, each with displacement ≥ 1 cm • Extension into the subtrochanteric region
Internal fixation of the fracture with a sliding hip screw or IM nail (devices approved by local regulatory agency), performed no later than 5 days after injury
Pre- and postoperative care performed as defined in Appendix J of the protocol
Subject or subject’s legally acceptable representative has provided informed consent |
|
E.4 | Principal exclusion criteria |
Conditions that may affect the ability to perform functional or clinical assessments required by the protocol, such as:
• Severe symptomatic osteoarthritis of the lower extremity • Inability to independently rise from armchair or walk 200 meters before hip fracture (use of unilateral assistive device or rolling walker is acceptable) • Cognitive deficit, as defined by Mini-Mental Status Examination score < 22 at time of randomization • Symptomatic neurological conditions such as Parkinson’s disease or persistent gross motor or sensory deficits such as hemiparesis or hemiplegia • Presence of concomitant injuries such as rib fractures, wrist fractures, or acute symptomatic vertebral fractures which severely impair the ability to rise from a chair • Associated extremity injuries including ipsilateral or contralateral fractures of the foot, tibia or fibula, wrist, humerus, femoral shaft, femoral head or hip dislocation, that may delay weight-bearing beyond one week after surgery
Use of bone grafts or bone substitutes at the time of fracture fixation
Head-injury, as defined by Glasgow Coma Scale <13 prior to randomization
Major polytrauma or significant axial trauma, with Injury Severity Score > 16
Pathological fracture or history of metabolic or bone disease that may interfere with the interpretation of the results, such as Paget’s disease, rheumatoid arthritis, osteomalacia, osteopetrosis, ankylosing spondylitis, Cushing’s disease, hyperprolactinemia
History of symptomatic spinal stenosis
History of facial nerve paralysis
Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical carcinoma in situ) within the last 5 years
Severe asthma or chronic obstructive pulmonary disease or recent exacerbation
Myocardial infarction or unstable angina pectoris within the last 12 months
Current alcohol dependence
History of solid organ or bone marrow transplants
Evidence of the following per subject report, chart review or local laboratory result (currently or within the past 5 years)
• Elevated transaminases (a) Serum aspartate aminotransferase ≥ 2.0 x upper limits of normal; (b) Serum alanine aminotransferase ≥ 2.0 x upper limits of normal • Significantly impaired renal function as determined by a derived creatinine clearance of ≤ 30 mL/min using the Modification of Diet in Renal Disease equation (Levey et al, 1999). The estimated glomerular filtration rate is calculated as follows: estimated glomerular filtration rate (mL/min/1.73m2) = 186 x [Serum creatinine (mg/dL)]-1.154 x [Age]-0.203 x [0.742 if subject is female] x [1.210 if subject is black]. • Current hypocalcemia or hypercalcemia (≥ 1.1 x upper limit of the normal range set by the local laboratory, after adequate volume resuscitation, is acceptable for high calcium value)
Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen
Use of the following agents affecting bone metabolism • Denosumab within the past 6 months • Fluoride (for osteoporosis) or IV bisphosphonates within the past 12 months • Parathyroid hormone or strontium within the past 12 months • Calcitonin within the past three months • Systemic glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than 10 days) within the past three months
BMP-2 or BMP-7 at the time of definitive fracture fixation
Subjects to be enrolled in DXA sub-study may not have had previous instrumentation with implants (ie, nails, screws, pins, plates) to either hip or lower spine
General
• Currently enrolled in another investigational device, drug, or biologics product study, or less than 30 days since ending another investigational device, drug, or biologics product study(s), or receiving other investigational agent(s). • Previous enrollment in an AMG 785 clinical study • Females of childbearing potential: Subject refuses to use 2 different forms of effective contraception (or true abstinence) in order to achieve a highly effective contraception result during treatment with study product and for an additional 5 months after the end of treatment with study product (5 months after the week 12 study visit) • Sexually active males with a female partner of childbearing potential: Subject in combination with his partner refuses to use 2 different forms of effective contraception (or true abstinence) in order to achieve a highly effective contraception result during treatment with study product and for an additional 3 months after the end of treatment with study product (3 months after the week 12 study visit) • Male subject with a partner who is pregnant: Subject refuses to use a condom during treatment with study product and for an additional 3 months after the end of treatment with study product (3 months after the week 12 study visit) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the difference in mean TUG over Weeks 6 through Week 20 between the AMG 785 and placebo groups.
|
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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 | 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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
End of study (EOS) is defined as the date the last eligible subject completes the final study visit at Week 52. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |