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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00907296




Registration number
NCT00907296
Ethics application status
Date submitted
21/05/2009
Date registered
21/05/2009
Date last updated
10/04/2019

Titles & IDs
Public title
Study of Romosozumab (AMG 785) in Tibial Diaphyseal Fractures Status Post Intramedullary Nailing
Scientific title
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
Secondary ID [1] 0 0
2008-008392-34
Secondary ID [2] 0 0
20062017
Universal Trial Number (UTN)
Trial acronym
STARTT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fracture Healing 0 0
Fracture Healing 0 0
Fracture Healing 0 0
Condition category
Condition code
Injuries and Accidents 0 0 0 0
Fractures
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Romosozumab
Treatment: Drugs - Placebo
Other interventions - Romosozumab
Treatment: Drugs - Placebo
Other interventions - Romosozumab
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12.

Experimental: 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.

Experimental: 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.

Experimental: Romosozumab 70 mg: 4 Doses - Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12.

Experimental: 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.

Experimental: 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.

Experimental: Romosozumab 140 mg: 4 Doses - Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12.

Experimental: 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.

Experimental: 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.

Experimental: Romosozumab 210 mg: 4 Doses - Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.

Placebo Comparator: Placebo - Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12.

Experimental: 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.

Experimental: 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.

Experimental: Romosozumab 70 mg: 4 Doses - Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12.

Experimental: 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.

Experimental: 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.

Experimental: Romosozumab 140 mg: 4 Doses - Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12.

Experimental: 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.

Experimental: 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.

Experimental: Romosozumab 210 mg: 4 Doses - Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.

Placebo Comparator: Placebo - Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12.

Experimental: 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.

Experimental: 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.

Experimental: Romosozumab 70 mg: 4 Doses - Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12.

Experimental: 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.

Experimental: 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.

Experimental: Romosozumab 140 mg: 4 Doses - Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12.

Experimental: 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.

Experimental: 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.

Experimental: Romosozumab 210 mg: 4 Doses - Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12.


Other interventions: Romosozumab
Administered by subcutaneous injection

Treatment: Drugs: Placebo
Administered by subcutaneous injection

Other interventions: Romosozumab
Administered by subcutaneous injection

Treatment: Drugs: Placebo
Administered by subcutaneous injection

Other interventions: Romosozumab
Administered by subcutaneous injection

Treatment: Drugs: Placebo
Administered by subcutaneous injection

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Radiographic Healing - 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.
Timepoint [1] 0 0
52 weeks
Primary outcome [2] 0 0
Time to Radiographic Healing - 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.
Timepoint [2] 0 0
52 weeks
Primary outcome [3] 0 0
Time to Radiographic Healing - 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.
Timepoint [3] 0 0
52 weeks
Secondary outcome [1] 0 0
Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain - The Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2, is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning domain includes 10 questions that assess limitations in physical activities because of health problems.
Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. The range of SF-36 physical functioning is 14.94 - 57.03. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement in physical functioning.
Timepoint [1] 0 0
Week 8 and weeks 12, 16, 20, 24, 36, and 52
Secondary outcome [2] 0 0
Number of Participants With Unplanned Revision Surgeries
Timepoint [2] 0 0
52 weeks
Secondary outcome [3] 0 0
Time to Clinical Healing - Time to clinical healing was defined as the time from the IM nailing surgery date to the first date that both the score for ability to bear weight on the fractured limb and the score for absence of pain at the fracture site were equal to 6.
The score for the ability to bear weight on the fractured limb was based on the ability to stand on affected leg without assistive device and the ability to walk without assistive device. The score ranges from 0 (unable to bear full body weight on the fractured limb) to 6 (able to bear full body weight on the fractured limb). Absence of pain at the fracture site was based on the absence of pain at the fracture site when applying direct pressure to the fracture site and applying a stress to the fracture site. The score ranges from 0 (pain without palpation at fracture site) to 6 (total absence of pain at fracture site).
Time to clinical healing was estimated using CIF; unplanned revision surgery was considered a competing risk in CIF estimate.
Timepoint [3] 0 0
52 weeks
Secondary outcome [4] 0 0
Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain - The Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2, is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning domain includes 10 questions that assess limitations in physical activities because of health problems.
Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. The range of SF-36 physical functioning is 14.94 - 57.03. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement in physical functioning.
Timepoint [4] 0 0
Week 8 and weeks 12, 16, 20, 24, 36, and 52
Secondary outcome [5] 0 0
Number of Participants With Unplanned Revision Surgeries
Timepoint [5] 0 0
52 weeks
Secondary outcome [6] 0 0
Time to Clinical Healing - Time to clinical healing was defined as the time from the IM nailing surgery date to the first date that both the score for ability to bear weight on the fractured limb and the score for absence of pain at the fracture site were equal to 6.
The score for the ability to bear weight on the fractured limb was based on the ability to stand on affected leg without assistive device and the ability to walk without assistive device. The score ranges from 0 (unable to bear full body weight on the fractured limb) to 6 (able to bear full body weight on the fractured limb). Absence of pain at the fracture site was based on the absence of pain at the fracture site when applying direct pressure to the fracture site and applying a stress to the fracture site. The score ranges from 0 (pain without palpation at fracture site) to 6 (total absence of pain at fracture site).
Time to clinical healing was estimated using CIF; unplanned revision surgery was considered a competing risk in CIF estimate.
Timepoint [6] 0 0
52 weeks
Secondary outcome [7] 0 0
Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain - The Medical Outcome Study Short Form 36-Item Health Survey (SF-36), Version 2, is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical functioning domain includes 10 questions that assess limitations in physical activities because of health problems.
Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. The range of SF-36 physical functioning is 14.94 - 57.03. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement in physical functioning.
Timepoint [7] 0 0
Week 8 and weeks 12, 16, 20, 24, 36, and 52
Secondary outcome [8] 0 0
Number of Participants With Unplanned Revision Surgeries
Timepoint [8] 0 0
52 weeks
Secondary outcome [9] 0 0
Time to Clinical Healing - Time to clinical healing was defined as the time from the IM nailing surgery date to the first date that both the score for ability to bear weight on the fractured limb and the score for absence of pain at the fracture site were equal to 6.
The score for the ability to bear weight on the fractured limb was based on the ability to stand on affected leg without assistive device and the ability to walk without assistive device. The score ranges from 0 (unable to bear full body weight on the fractured limb) to 6 (able to bear full body weight on the fractured limb). Absence of pain at the fracture site was based on the absence of pain at the fracture site when applying direct pressure to the fracture site and applying a stress to the fracture site. The score ranges from 0 (pain without palpation at fracture site) to 6 (total absence of pain at fracture site).
Time to clinical healing was estimated using CIF; unplanned revision surgery was considered a competing risk in CIF estimate.
Timepoint [9] 0 0
52 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Research Site - Geelong
Recruitment hospital [2] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
3220 - Geelong
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Blagoevgrad
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Pleven
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Plovdiv
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Ruse
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Sofia
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Denmark
State/province [20] 0 0
Hvidovre
Country [21] 0 0
Denmark
State/province [21] 0 0
København NV
Country [22] 0 0
Denmark
State/province [22] 0 0
Ã…rhus C
Country [23] 0 0
Estonia
State/province [23] 0 0
Tallinn
Country [24] 0 0
Estonia
State/province [24] 0 0
Tartu
Country [25] 0 0
France
State/province [25] 0 0
Lille
Country [26] 0 0
France
State/province [26] 0 0
Marseille
Country [27] 0 0
France
State/province [27] 0 0
Nantes Cedex 1
Country [28] 0 0
France
State/province [28] 0 0
Paris Cedex 12
Country [29] 0 0
Germany
State/province [29] 0 0
Aachen
Country [30] 0 0
Germany
State/province [30] 0 0
Hamburg
Country [31] 0 0
Germany
State/province [31] 0 0
Hannover
Country [32] 0 0
Germany
State/province [32] 0 0
Mannheim
Country [33] 0 0
Germany
State/province [33] 0 0
Muenster
Country [34] 0 0
Greece
State/province [34] 0 0
Athens
Country [35] 0 0
Greece
State/province [35] 0 0
Larissa
Country [36] 0 0
Greece
State/province [36] 0 0
Patra
Country [37] 0 0
Greece
State/province [37] 0 0
Thessaloniki
Country [38] 0 0
Hong Kong
State/province [38] 0 0
Hong Kong
Country [39] 0 0
Hong Kong
State/province [39] 0 0
New Territories
Country [40] 0 0
Hungary
State/province [40] 0 0
Budapest
Country [41] 0 0
Hungary
State/province [41] 0 0
Miskolc
Country [42] 0 0
Hungary
State/province [42] 0 0
Nyiregyhaza
Country [43] 0 0
Hungary
State/province [43] 0 0
Szeged
Country [44] 0 0
India
State/province [44] 0 0
Karnataka
Country [45] 0 0
India
State/province [45] 0 0
Maharashtra
Country [46] 0 0
India
State/province [46] 0 0
Rajasthan
Country [47] 0 0
India
State/province [47] 0 0
Tamil Nadu
Country [48] 0 0
India
State/province [48] 0 0
Gandhinagar
Country [49] 0 0
India
State/province [49] 0 0
Mangalore
Country [50] 0 0
India
State/province [50] 0 0
Nashik
Country [51] 0 0
Italy
State/province [51] 0 0
Firenze
Country [52] 0 0
Italy
State/province [52] 0 0
Milano
Country [53] 0 0
Italy
State/province [53] 0 0
Pisa
Country [54] 0 0
Italy
State/province [54] 0 0
Roma (RM)
Country [55] 0 0
Italy
State/province [55] 0 0
Verona
Country [56] 0 0
Latvia
State/province [56] 0 0
Liepaja
Country [57] 0 0
Latvia
State/province [57] 0 0
Riga
Country [58] 0 0
Latvia
State/province [58] 0 0
Valmiera
Country [59] 0 0
Lithuania
State/province [59] 0 0
Kaunas
Country [60] 0 0
Lithuania
State/province [60] 0 0
Vilnius
Country [61] 0 0
Mexico
State/province [61] 0 0
Nuevo León
Country [62] 0 0
New Zealand
State/province [62] 0 0
Christchurch
Country [63] 0 0
New Zealand
State/province [63] 0 0
Tauranga
Country [64] 0 0
Norway
State/province [64] 0 0
Kongsvinger
Country [65] 0 0
Poland
State/province [65] 0 0
Bialystok
Country [66] 0 0
Poland
State/province [66] 0 0
Bytom
Country [67] 0 0
Poland
State/province [67] 0 0
Krakow
Country [68] 0 0
Poland
State/province [68] 0 0
Kraków
Country [69] 0 0
Poland
State/province [69] 0 0
Lublin
Country [70] 0 0
Romania
State/province [70] 0 0
Bucharest
Country [71] 0 0
Romania
State/province [71] 0 0
Bucuresti
Country [72] 0 0
Romania
State/province [72] 0 0
Timisoara
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Moscow
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Saint Petersburg
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Yaroslavl
Country [76] 0 0
Slovakia
State/province [76] 0 0
Bratislava
Country [77] 0 0
Slovakia
State/province [77] 0 0
Nitra
Country [78] 0 0
Slovakia
State/province [78] 0 0
Piestany
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Leeds
Country [80] 0 0
United Kingdom
State/province [80] 0 0
London
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Newcastle
Country [82] 0 0
United Kingdom
State/province [82] 0 0
Norwich
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Oxford
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Stanmore

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
UCB Pharma
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
UCB Pharma
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
UCB Pharma
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT00907296
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications