A Multi-center, Randomized, Double Blind, Placebo-controlled Study of AMG 785 in Skeletally Mature Adults With a Fresh Unilateral Tibial Diaphyseal Fracture Status Post Definitive Fracture Fixation With an Intramedullary Nail
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Amgen
- Enrollment
- 402
- Locations
- 1
- Primary Endpoint
- Time to Radiographic Healing
Study Overview
Brief Summary
The primary objective of this study is to investigate the effect of romosozumab compared with placebo on time to radiographic healing of fresh tibial diaphyseal fractures (fractures in the midsection of the shinbone).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Skeletally mature adults, age 18 to 85 years with radiographically closed growth plates
- •Fresh unilateral closed or Gustilo type I or type II open tibial fracture
- •Definitive fracture fixation with reamed (closed and open fractures) or unreamed (open fractures only) intramedullary nailing
Exclusion Criteria
- •Major polytrauma or significant axial trauma
- •Associated lower extremity fracture that will delay subject's ability to bear weight beyond the normal time expected for a tibial shaft fracture
- •Use of bone grafts at the time of fracture fixation
- •Pathological fracture or metabolic or bone disease
- •History of symptomatic spinal stenosis or facial nerve paralysis
- •Malignancy within the last 5 years
- •Evidence of the following (currently or within the past 5 years): elevated transaminases, significantly impaired renal function, current hyper- or hypocalcaemia
- •Use of agents affecting bone metabolism
- •Subject refuses to use appropriate methods of contraception
Arms & Interventions
Romosozumab 140 mg: 2 Doses
Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12.
Intervention: Romosozumab (Biological)
Romosozumab 70 mg: 4 Doses
Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12.
Intervention: Romosozumab (Biological)
Romosozumab 70 mg: 3 Doses
Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12.
Intervention: Romosozumab (Biological)
Romosozumab 70 mg: 2 Doses
Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12.
Intervention: Romosozumab (Biological)
Placebo
Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12.
Intervention: Placebo (Drug)
Romosozumab 210 mg: 4 Doses
Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.
Intervention: Romosozumab (Biological)
Romosozumab 210 mg: 3 Doses
Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12.
Intervention: Romosozumab (Biological)
Romosozumab 210 mg: 2 Doses
Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12.
Intervention: Romosozumab (Biological)
Romosozumab 140 mg: 4 Doses
Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12.
Intervention: Romosozumab (Biological)
Romosozumab 140 mg: 3 Doses
Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12.
Intervention: Romosozumab (Biological)
Outcomes
Primary Outcomes
Time to Radiographic Healing
Time Frame: 52 weeks
Time to radiographic healing was defined as the time from intramedullary (IM) nailing to the first occurrence of bridging of 3 out of 4 cortices. Radiographic fracture healing was determined by a panel of independent reviewers (orthopedic/trauma surgeons and radiologists) blinded to treatment. The cumulative incidence function (CIF) method was used to estimate the median time to radiographic healing and the confidence intervals. Unplanned revision surgery to promote healing was considered a competing risk in CIF estimate.
Secondary Outcomes
- Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain(Week 8 and weeks 12, 16, 20, 24, 36, and 52)
- Number of Participants With Unplanned Revision Surgeries(52 weeks)
- Time to Clinical Healing(52 weeks)