Fracture HealingPhase 2STARTTNCT00907296
Study of Romosozumab (AMG 785) in Tibial Diaphyseal Fractures Status Post Intramedullary Nailing
A Phase 2 study testing Romosozumab in people with Fracture Healing, run by Amgen at 103 sites in 23 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Fracture Healing
- What is being tested?
- Romosozumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 402 participants
- Where
- 103 sitesin 23 countries
- Study dates
- 2 Sep 2009to 10 May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
103 sites in 23 countries.
103 sites in 23 countries
United States14 sites
Research Site
Altoona, Pennsylvania, 16602
Research Site
Aurora, Colorado, 80012
Research Site
Birmingham, Alabama, 35294
Research Site
Brooklyn, New York, 11220
Research Site
Columbia, South Carolina, 29203
Research Site
Denver, Colorado, 80204
Research Site
Detroit, Michigan, 48202
Research Site
Indianapolis, Indiana, 46202
Research Site
Jacksonville, Florida, 32209
Research Site
Orange, California, 92868
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Rochester, New York, 14642
Research Site
Sandy City, Utah, 84070
Research Site
St Louis, Missouri, 63110
India9 sites
Research Site
Bangalore, Karnataka, 560 034
Research Site
Bangalore, Karnataka, 560 054
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Gandhinagar, 382 428
Research Site
Jaipur, Rajasthan, 302 022
Research Site
Madurai, Tamil Nadu, 625 020
Research Site
Mangalore, Karnataka, 575 002
Research Site
Mangalore, 575 001
Research Site
Nashik, 422 009
Research Site
Pune, Maharashtra, 411 005
Canada8 sites
Research Site
Ajax, Ontario, L1S 2J5
Research Site
Montreal, Quebec, H3G 1A4
Research Site
Montreal, Quebec, H4J 1C5
Research Site
Red Deer, Alberta, T4N 6V7
Research Site
Thunder Bay, Ontario, P7B 7C7
Research Site
Toronto, Ontario, M5C 1R6
Research Site
Waterloo, Ontario, N2J 1C4
Research Site
Windsor, Ontario, N9A 1E1
Russia7 sites
Research Site
Moscow, 115280
Research Site
Moscow, 117292
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Moscow, 119049
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Moscow, 127299
Research Site
Moscow, 129327
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Saint Petersburg, 196247
Research Site
Yaroslavl, 150003
Italy6 sites
Research Site
Florence, 50139
Research Site
Milan, 20122
Research Site
Milan, 20142
Research Site
Pisa, 56126
Research Site
Roma (RM), 00133
Research Site
Verona, 37126
United Kingdom6 sites
Research Site
Leeds, LS1 3EX
Research Site
London, E1 1BB
Research Site
Newcastle, NE1 4LP
Research Site
Norwich, NR4 7UY
Research Site
Oxford, OX3 9DU
Research Site
Stanmore, HA7 4LP
Bulgaria5 sites
Research Site
Blagoevgrad, 2700
Research Site
Pleven, 5800
Research Site
Plovdiv, 4002
Research Site
Rousse, 7000
Research Site
Sofia, 1527
Germany5 sites
Research Site
Aachen, 52074
Research Site
Hamburg, 20246
Research Site
Hanover, 30625
Research Site
Mannheim, 68165
Research Site
Münster, 48149
Greece5 sites
Research Site
Athens, 12462
Research Site
Athens, 14561
Research Site
Larissa, 41110
Research Site
Pátrai, 26500
Research Site
Thessaloniki, 56429
Poland5 sites
Research Site
Bialystok, 15-276
Research Site
Bytom, 41-902
Research Site
Kraków, 31-826
Research Site
Krakow, 30-901
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Lublin, 20-718
France4 sites
Research Site
Lille, 59000
Research Site
Marseille, 13009
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Nantes, 44035
Research Site
Paris, 75571
Hungary4 sites
Research Site
Budapest, 1081
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Miskolc, 3526
Research Site
Nyíregyháza, 4400
Research Site
Szeged, 6725
Latvia4 sites
Research Site
Liepāja, 3400
Research Site
Riga, 1004
Research Site
Riga, 1005
Research Site
Valmiera, 4201
Denmark3 sites
Research Site
Ã…rhus C, 8000
Research Site
Hvidovre, 2650
Research Site
København NV, 2400
Romania3 sites
Research Site
Bucharest, 014461
Research Site
Bucharest, 050098
Research Site
Timișoara, 300736
Slovakia3 sites
Research Site
Bratislava, 833 05
Research Site
Nitra, 950 01
Research Site
Piešťany, 921 01
Australia2 sites
Research Site
Geelong, Victoria, 3220
Research Site
Parkville, Victoria, 3050
New Zealand2 sites
Research Site
Christchurch, 8022
Research Site
Tauranga, 3143
About this study
Official 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
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).
- Conditions
- Fracture Healing
- Being tested
- Romosozumab, Placebo
- Keywords
- Fracture Healing, Tibial Diaphyseal Fracture
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomosozumabBiological
Also called AMG 785, Evenity
Administered by subcutaneous injection
PlaceboDrug
Administered by subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. Receives: Drug: Placebo |
| Romosozumab 70 mg: 2 Doses | Experimental | Participants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Receives: Biological: Romosozumab |
| Romosozumab 70 mg: 3 Doses | Experimental | Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Receives: Biological: Romosozumab |
| Romosozumab 70 mg: 4 Doses | Experimental | Participants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. Receives: Biological: Romosozumab |
| Romosozumab 140 mg: 2 Doses | Experimental | Participants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Receives: Biological: Romosozumab |
| Romosozumab 140 mg: 3 Doses | Experimental | Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Receives: Biological: Romosozumab |
| Romosozumab 140 mg: 4 Doses | Experimental | Participants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. Receives: Biological: Romosozumab |
| Romosozumab 210 mg: 2 Doses | Experimental | Participants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. Receives: Biological: Romosozumab |
| Romosozumab 210 mg: 3 Doses | Experimental | Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. Receives: Biological: Romosozumab |
| Romosozumab 210 mg: 4 Doses | Experimental | Participants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12. Receives: Biological: Romosozumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 52 weeks
Secondary outcomes (3)
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.
Measured: Week 8 and weeks 12, 16, 20, 24, 36, and 52
Number of Participants With Unplanned Revision Surgeries
Measured: 52 weeks
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.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2009 (estimated)
- Study start2 Sep 2009
- Primary completion6 Mar 2012
- Study completion10 May 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fracture HealingStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 402 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- UCB Pharma
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00907296
- Sponsor's protocol ID
- 20062017
- Other IDs
- 2008-008392-34, 2008
- Acronym
- STARTT
- Status last verified
- Sep 2022
- First submitted
- 21 May 2009
- Last updated
- 22 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bhandari M, Schemitsch EH, Karachalios T, Sancheti P, Poolman RW, Caminis J, Daizadeh N, Dent-Acosta RE, Egbuna O, Chines A, Miclau T. Romosozumab in Skeletally Mature Adults with a Fresh Unilateral Tibial Diaphyseal Fracture: A Randomized Phase-2 Study. J Bone Joint Surg Am. 2020 Aug 19;102(16):1416-1426. doi: 10.2106/JBJS.19.01008.
PubMed 32358413
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00907296
- Acronym / sponsor ID
- STARTT / 20062017
- Conditions
- Fracture Healing
- Keywords
- Fracture Healing, Tibial Diaphyseal Fracture
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 402 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- UCB Pharma
- Study start
- 2 Sep 2009 (actual)
- Primary completion
- 6 Mar 2012 (actual)
- Study completion
- 10 May 2013 (actual)
- First posted
- 22 May 2009 (estimated)
- Results
- Posted 1 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants received subcutaneous injections of matching placebo on day 1 and at weeks 2, 6, and 12. |
| Romosozumab 70 mg: 2 Doses | Experimental | Biological: RomosozumabParticipants received subcutaneous injections of 70 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. |
| Romosozumab 70 mg: 3 Doses | Experimental | Biological: RomosozumabParticipants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. |
| Romosozumab 70 mg: 4 Doses | Experimental | Biological: RomosozumabParticipants received subcutaneous injections of 70 mg romosozumab on day 1 and weeks 2, 6, and 12. |
| Romosozumab 140 mg: 2 Doses | Experimental | Biological: RomosozumabParticipants received subcutaneous injections of 140 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. |
| Romosozumab 140 mg: 3 Doses | Experimental | Biological: RomosozumabParticipants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. |
| Romosozumab 140 mg: 4 Doses | Experimental | Biological: RomosozumabParticipants received subcutaneous injections of 140 mg romosozumab on day 1 and weeks 2, 6, and 12. |
| Romosozumab 210 mg: 2 Doses | Experimental | Biological: RomosozumabParticipants received subcutaneous injections of 210 mg romosozumab on day 1 and week 2, and matching placebo at weeks 6 and 12. |
| Romosozumab 210 mg: 3 Doses | Experimental | Biological: RomosozumabParticipants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2 and 6, and matching placebo at week 12. |
| Romosozumab 210 mg: 4 Doses | Experimental | Biological: RomosozumabParticipants received subcutaneous injections of 210 mg romosozumab on day 1 and weeks 2, 6, and 12. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RomosozumabAlso: AMG 785, EvenityAdministered by subcutaneous injection | Biological | Romosozumab 140 mg: 2 Doses, Romosozumab 140 mg: 3 Doses, Romosozumab 140 mg: 4 Doses, Romosozumab 210 mg: 2 Doses, Romosozumab 210 mg: 3 Doses, Romosozumab 210 mg: 4 Doses, Romosozumab 70 mg: 2 Doses, Romosozumab 70 mg: 3 Doses, Romosozumab 70 mg: 4 Doses |
| PlaceboAdministered by subcutaneous injection | Drug | Placebo |
Primary outcome
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.
3 secondary outcomes
Change From Week 8 in Short Form (36) Health Survey Physical Functioning Domain
Time frame: Week 8 and weeks 12, 16, 20, 24, 36, and 52
Number of Participants With Unplanned Revision Surgeries
Time frame: 52 weeks
Time to Clinical Healing
Time frame: 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32358413Bhandari M, Schemitsch EH, Karachalios T, Sancheti P, Poolman RW, Caminis J, Daizadeh N, Dent-Acosta RE, Egbuna O, Chines A, Miclau T. Romosozumab in Skeletally Mature Adults with a Fresh Unilateral Tibial Diaphyseal Fracture: A Randomized Phase-2 Study. J Bone Joint Surg Am. 2020 Aug 19;102(16):1416-1426. doi: 10.2106/JBJS.19.01008.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
103 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Romosozumab in people with Fracture Healing, run by Amgen at 103 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 103 sites in United States, India, Canada, Russia, Italy and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Radiographic Healing (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00907296, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2022.