Study To Assess FRacTure Healing With SclerosTin Antibody - Hip (STARTT-Hip)

A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy, Safety, and Tolerability of AMG 785 in Adults With a Fresh Unilateral Hip Fracture, Status Post Surgical Fixation

This is an international, multi-center study to determine the efficacy, safety, and tolerability of romosozumab (AMG 785) in adults with a fresh unilateral hip fracture, status post surgical fixation.

Study Overview

• Status: Completed
• Conditions: Fracture Healing
• Intervention / Treatment: Drug: Romosozumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 332
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1012AAR
    • Research Site
  • Buenos Aires, Argentina, C1419AHN
    • Research Site
• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Research Site
  • Victoria
    • Footscray, Victoria, Australia, 3011
      • Research Site
• Belgium
  • Brugge, Belgium, 8000
    • Research Site
  • Genk, Belgium, 3600
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liege, Belgium, 4000
    • Research Site
  • Liège, Belgium, 4020
    • Research Site
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Research Site
  • Pleven, Bulgaria, 5800
    • Research Site
  • Plovdiv, Bulgaria, 4002
    • Research Site
• Canada
  • Quebec, Canada, G1R 2J6
    • Research Site
  • Quebec, Canada, G1J 1Z4
    • Research Site
  • Alberta
    • Red Deer, Alberta, Canada, T4N 6V7
      • Research Site
  • Ontario
    • Cambridge, Ontario, Canada, N1R 3G2
      • Research Site
    • Guelph, Ontario, Canada, N1E 4J4
      • Research Site
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Research Site
    • Toronto, Ontario, Canada, M5C 1R6
      • Research Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Research Site
• Denmark
  • Hvidovre, Denmark, 2650
    • Research Site
  • København NV, Denmark, 2400
    • Research Site
  • Viborg, Denmark, 8800
    • Research Site
  • Ã…rhus C, Denmark, 8000
    • Research Site
• Estonia
  • Tallinn, Estonia, 11312
    • Research Site
  • Tartu, Estonia, 50410
    • Research Site
• Finland
  • Kuopio, Finland, 70211
    • Research Site
  • Oulu, Finland, 90220
    • Research Site
  • Turku, Finland, 20520
    • Research Site
• Germany
  • Aachen, Germany, 52074
    • Research Site
  • Berlin, Germany, 12200
    • Research Site
  • Muenchen, Germany, 80336
    • Research Site
  • Muenster, Germany, 48149
    • Research Site
• Greece
  • Athens, Greece, 12462
    • Research Site
  • Athens, Greece, 14561
    • Research Site
  • Larissa, Greece, 41110
    • Research Site
  • Patra, Greece, 26500
    • Research Site
  • Thessaloniki, Greece, 56429
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • New Territories, Hong Kong
    • Research Site
• Hungary
  • Budapest, Hungary, 1081
    • Research Site
  • Miskolc, Hungary, 3526
    • Research Site
  • Nyiregyhaza, Hungary, 4400
    • Research Site
  • Szeged, Hungary, 6725
    • Research Site
• India
  • Mangalore, India, 575 001
    • Research Site
  • Nashik, India, 422 009
    • Research Site
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500 063
      • Research Site
  • Karnataka
    • Bangalore, Karnataka, India, 560 054
      • Research Site
    • Mangalore, Karnataka, India, 575 002
      • Research Site
  • Maharashtra
    • Nashik, Maharashtra, India, 422 002
      • Research Site
    • Pune, Maharashtra, India, 411 005
      • Research Site
    • Pune, Maharashtra, India, 411 044
      • Research Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302 022
      • Research Site
• Italy
  • Firenze, Italy, 50139
    • Research Site
  • Milano, Italy, 20142
    • Research Site
  • Roma (RM), Italy, 00133
    • Research Site
  • Verona, Italy, 37126
    • Research Site
• Latvia
  • Riga, Latvia, 1005
    • Research Site
  • Valmiera, Latvia, 4201
    • Research Site
• Lithuania
  • Kaunas, Lithuania, 44320
    • Research Site
  • Vilnius, Lithuania, 04130
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1091 AC
    • Research Site
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site
  • Amsterdam, Netherlands, 1061 AE
    • Research Site
  • Haarlem, Netherlands, 2035 RC
    • Research Site
  • Nieuwegein, Netherlands, 3435 CM
    • Research Site
• New Zealand
  • Christchurch, New Zealand, 8022
    • Research Site
• Poland
  • Kraków, Poland, 31-826
    • Research Site
  • Lublin, Poland, 20-718
    • Research Site
  • Warszawa, Poland, 03-242
    • Research Site
  • Warszawa, Poland, 00-739
    • Research Site
• Slovenia
  • Celje, Slovenia, 3000
    • Research Site
  • Izola, Slovenia, 6310
    • Research Site
  • Jesenice, Slovenia, 4270
    • Research Site
  • Sempeter pri Gorici, Slovenia, 5290
    • Research Site
• Sweden
  • Linköping, Sweden, 581 85
    • Research Site
  • Lund, Sweden, 221 85
    • Research Site
• Switzerland
  • Basel, Switzerland, 4031
    • Research Site
  • Lausanne, Switzerland, 1011
    • Research Site
  • Luzern, Switzerland, 6000
    • Research Site
  • Zurich, Switzerland, 8063
    • Research Site
• United Kingdom
  • Barnet, United Kingdom, EN5 3DJ
    • Research Site
  • Leeds, United Kingdom, LS1 3EX
    • Research Site
  • London, United Kingdom, E1 1BB
    • Research Site
  • Newcastle, United Kingdom, NE1 4LP
    • Research Site
  • Norwich, United Kingdom, NR4 7UY
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Research Site
  • California
    • Pomona, California, United States, 91767
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Research Site
    • Denver, Colorado, United States, 80204
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Research Site
  • Minnesota
    • Woodbury, Minnesota, United States, 55125
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11220
      • Research Site
    • Rochester, New York, United States, 14642
      • Research Site
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
    • State College, Pennsylvania, United States, 16801
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females, age 55 to 95 years
• fresh unilateral low energy intertrochanteric or femoral neck fracture as the primary injury, confirmed by X-ray and in the opinion of the treating surgeon amenable to repair by internal fixation

• internal fixation of the fracture with devices approved by local regulatory agency, performed no later than 7 days after injury for intertrochanteric or undisplaced femoral neck fractures and no later than 2 days after injury for displaced femoral neck fractures

  • intertrochanteric fracture: sliding hip screw or IM nail
  • femoral neck fracture: sliding hip screw or at least 3 cancellous screws

Exclusion Criteria:

• severe symptomatic osteoarthritis of the lower extremity
• inability to independently rise from armchair or walk 200 meters before hip fracture
• 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
• head-injury, as defined by Glasgow Coma Scale < 13 prior to randomization
• use of bone grafts or bone substitutes at the time of fracture fixation
• major polytrauma or significant axial trauma, with Injury Severity Score > 16
• pathological fracture or history of metabolic or bone disease (except osteoporosis) 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 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 elevated transaminases (≥ 2.0 x upper limits of normal) or significantly impaired renal function (creatinine clearance of ≤ 30 mL/min)
• evidence of current hypercalcemia or hypocalcemia (outside of 1.1 x the normal range)
• bone morphogenic proteins (BMP)-2 or BMP-7 at the time of definitive fracture fixation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo to romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Drug: Placebo; Administered by subcutaneous (under the skin) injection
Experimental: Romosozumab 70 mg; Participants received 70 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785; Evenity
Experimental: Romosozumab 140 mg; Participants received 140 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785; Evenity
Experimental: Romosozumab 210 mg; Participants received 210 mg romosozumab administered by subcutaneous injection on day 1 and at weeks 2, 6, and 12.	Drug: Romosozumab; Administered by subcutaneous injection; Other Names: AMG 785; Evenity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Timed-Up-and-Go (TUG) Over Week 6 Through Week 20	Functional healing was measured by the timed-up-and-go test (TUG) over Weeks 6 through 20. During this assessment, the clinician timed the participant while they stood up from a seated position in a chair, walked three meters, turned around, walked three meters back to the chair, and returned to the seated position. A TUG value of ten seconds or less was considered normal for a healthy elderly person. Higher TUG values after hip fracture have been shown to be a predictor of future falls. Least squares mean (LSM) estimates were based on a repeated measures model fitted with the log-transformed TUG values at weeks 2, 6, 12, 16, 20, 24, 36, 52 as the dependent variable and adjusted for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction and back-transformed using the exponential transformation.	Weeks 6, 12, 16, and 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Timed-Up-and-Go (TUG) at Each Visit	During the timed-up-and-go test the clinician timed the participant while they stood up from a seated position in a chair, walked 3 meters, turned around, walked 3 meters back to the chair, and returned to a seated position. A TUG value of ≤ 10 seconds is considered normal for a healthy elderly person. LSMs were based on a repeated measures model adjusting for treatment, randomized strata, gender, country category, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction. Missing TUG values for participants still on study were imputed using the last observation carried forward (LOCF) when possible. If no observation could be carried forward, the maximum TUG value observed among all participants at a given visit was used. TUG values obtained after unplanned revision surgery were replaced by carrying forward the last available observed or imputed value prior to unplanned revision surgery.	Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Time to Radiographic Healing	Time to radiographic healing is the time interval from the surgery date for the eligible hip fracture to the date of radiographic healing, defined as effacement of the fracture lines by newly formed bone along the cortices and within the trabecular bone on anteroposterior and lateral (or oblique) radiographs. Radiographic fracture healing was determined by a panel of independent reviewers 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.	52 weeks
Radiographic Union Scale for Hip (RUSH) Score At Each Visit	The radiographic Union Scale for Hip (RUSH) is a semiquantitative scoring assessment to assess hip fracture healing after surgical repair. The RUSH has 4 key domains based on radiographic parameters used by orthopedic surgeons and radiologists in routine clinical practice including cortical bridging (4 to 12 points), cortical fracture line disappearance (4 to 12 points), trabecular consolidation (1 to 3 points), and trabecular index disappearance of fracture line (1 to 3 points). The score has a minimum of 10 points (definitely not healed) and a maximum of 30 points (definitely healed).	Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Harris Hip Score At Each Visit	The Harris Hip Score is a clinician-based outcome that assesses pain, function, deformity, and range of motion. The pain domain measures pain severity and its effect on activities and need for pain medication. The function domain consists of daily activities and gait. Deformity takes into account hip flexion, adduction, internal rotation, and extremity length discrepancy. Range of motion measures hip flexion, abduction, external and internal rotation, and adduction. The score ranges form 0-100 (best possible outcome) covering pain (0-44 points), function (0-47 points), absence of deformity (4 points), and range of motion (5 points). LSMs were based on a repeated measures model fitted with the Harris hip score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.	Weeks 2, 6, 12, 16, 20, 24, 36, and 52
Hip Pain Score at Each Visit	Hip pain was assessed using a visual analog scale (VAS). Participants were asked to rate their pain as a result of the hip fracture on a 100 mm vertical scale with 0 indicating no pain at all and 100 indicating the worst pain they could imagine. LSMs were based on a repeated measures model fitted with hip pain score values at weeks 2, 6, 12, 16, 20, 24, 36, and 52 as the dependent variable and adjusted for treatment, randomized strata, gender, pre-fracture community-dwelling status, pre-fracture walking aid use, quality of surgical fixation, visit, and treatment-by-visit interaction.	Weeks 2, 6, 12, 16, 20, 24, 36, and 52

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Schemitsch EH, Miclau T, Karachalios T, Nowak LL, Sancheti P, Poolman RW, Caminis J, Daizadeh N, Dent-Acosta RE, Egbuna O, Chines A, Maddox J, Grauer A, Bhandari M. A Randomized, Placebo-Controlled Study of Romosozumab for the Treatment of Hip Fractures. J Bone Joint Surg Am. 2020 Apr 15;102(8):693-702. doi: 10.2106/JBJS.19.00790.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2010
• Primary Completion (Actual): June 30, 2012
• Study Completion (Actual): May 10, 2013

Study Registration Dates

• First Submitted: March 4, 2010
• First Submitted That Met QC Criteria: March 4, 2010
• First Posted (Estimate): March 5, 2010

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 8, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Hip Fracture; Fracture Healing; AMG 785; Proximal Femur
• Additional Relevant MeSH Terms: Wounds and Injuries; Fractures, Bone
• Other Study ID Numbers: 20080394