Study of AMG 785 in Tibial Diaphyseal Fractures Status Post Intramedullary Nailing

• Conditions: Acceleration of fracture healing; MedDRA version: 14.1Level: PTClassification code 10043827Term: Tibia fractureSystem Organ Class: 10022117 - Injury, poisoning and procedural complications; Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

• Registration Number: EUCTR2008-008392-34-DE
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-22
• Last Update Posted: 8 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

Skeletally mature adults, age = 18 to = 85 years at randomization, with radiographically closed growth plates.

Fresh unilateral closed or Gustilo type I or type II open tibia diaphyseal fracture (fracture line must not extend into the ankle or knee joint) as the primary injury.

For closed fractures: Definitive fracture fixation with reamed IM nailing (modern, statically, interlocking nail) performed no later than 14 days after injury.

For Gustilo type I/II open fractures: Definitive fracture fixation with reamed or unreamed IM nailing (modern, statically, interlocking nail) performed no later than 24 hours after injury.
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 370
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

Major polytrauma or significant axial trauma, with injury severity score >16

Head-injury, as defined by Glasgow Coma Scale <13 at time of randomization

Associated fracture of the lower extremity or any other condition that, in the opinion of the surgeon, will delay the subject’s ability to bear weight beyond the normal time expected for a tibial shaft fracture

Use of bone grafts at the time of definitive fracture fixation

History of pathological fracture or metabolic or bone disease that may interfere with the interpretation of the results, such as Paget’s disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing’s disease, hyperprolactinemia

History of symptomatic spinal stenosis that has not been surgically corrected. If surgically corrected, the subject must be asymptomatic to be eligible for the study

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

History of solid organ or bone marrow transplants

Evidence of any 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 (AST; serum glutamate-oxaloacetic transaminase [SGOT]) = 2.0 x upper limits of normal; (b) Serum alanine aminotransferase (ALT; serum glutamate-pyruvate transaminase [SGPT]) = 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].

Per subject report, chart review or local laboratory result, evidence of current hypercalcemia or hypocalcemia, outside of 1.1x the normal range set by the local laboratory

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:
• Intravenous bisphosphonates at any time
• Denosumab at any time
• Fluoride (for osteoporosis) within the past 24 months
• Oral bisphosphonates, parathyroid hormone or strontium within the past 12 months
• Calcitonin, selective estrogen receptor modulators, systemic oral or transdermal estrogen within the past three months (estrogen-containing contraceptive therapy is permitted)
• Systemic glucocorticosteroids (= 5 mg prednisone equivalent per day for more than 10 days) within the past three months
• Tibolone within the past three months
• BMP-2 or BMP-7 at the time of definitive fracture fixation

Current use of anticoagulants (doses for deep vein thrombosis prophylaxis are permitted)

General
• Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s)
• Previous enrollment in an AMG 785 clinical study
• Subject of child-bearing potential who is pregnant (eg, positive human chorionic gonadotropin test) or is breast-feeding

• Females of childbear

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified