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

Fracture Healing Clinical Trial

— STARTT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00907296
• Other study ID #: 20062017
• Secondary ID: 2008-008392-34
• Status: Completed
• Phase: Phase 2
• Start date: September 2, 2009
• Est. completion date: May 10, 2013

Study information

• Verified date: September 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 402
• Est. completion date: May 10, 2013
• Est. primary completion date: March 6, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Fracture Healing
• Fractures, Bone

Intervention

Biological:
• Romosozumab
Administered by subcutaneous injection

Drug:
• Placebo
Administered by subcutaneous injection

Locations

Country	Name	City	State
Australia	Research Site	Geelong	Victoria
Australia	Research Site	Parkville	Victoria
Bulgaria	Research Site	Blagoevgrad
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sofia
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Red Deer	Alberta
Canada	Research Site	Thunder Bay	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Waterloo	Ontario
Canada	Research Site	Windsor	Ontario
Denmark	Research Site	Ã…rhus C
Denmark	Research Site	Hvidovre
Denmark	Research Site	København NV
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
France	Research Site	Lille
France	Research Site	Marseille
France	Research Site	Nantes Cedex 1
France	Research Site	Paris Cedex 12
Germany	Research Site	Aachen
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Mannheim
Germany	Research Site	Muenster
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Larissa
Greece	Research Site	Patra
Greece	Research Site	Thessaloniki
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	New Territories
Hungary	Research Site	Budapest
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyiregyhaza
Hungary	Research Site	Szeged
India	Research Site	Bangalore	Karnataka
India	Research Site	Bangalore	Karnataka
India	Research Site	Gandhinagar
India	Research Site	Jaipur	Rajasthan
India	Research Site	Madurai	Tamil Nadu
India	Research Site	Mangalore
India	Research Site	Mangalore	Karnataka
India	Research Site	Nashik
India	Research Site	Pune	Maharashtra
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Pisa
Italy	Research Site	Roma (RM)
Italy	Research Site	Verona
Latvia	Research Site	Liepaja
Latvia	Research Site	Riga
Latvia	Research Site	Riga
Latvia	Research Site	Valmiera
Lithuania	Research Site	Kaunas
Lithuania	Research Site	Vilnius
Mexico	Research Site	Monterrey	Nuevo León
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Tauranga
Norway	Research Site	Kongsvinger
Poland	Research Site	Bialystok
Poland	Research Site	Bytom
Poland	Research Site	Kraków
Poland	Research Site	Krakow
Poland	Research Site	Lublin
Romania	Research Site	Bucharest
Romania	Research Site	Bucuresti
Romania	Research Site	Timisoara
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Yaroslavl
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Nitra
Slovakia	Research Site	Piestany
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Newcastle
United Kingdom	Research Site	Norwich
United Kingdom	Research Site	Oxford
United Kingdom	Research Site	Stanmore
United States	Research Site	Altoona	Pennsylvania
United States	Research Site	Aurora	Colorado
United States	Research Site	Birmingham	Alabama
United States	Research Site	Brooklyn	New York
United States	Research Site	Columbia	South Carolina
United States	Research Site	Denver	Colorado
United States	Research Site	Detroit	Michigan
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Jacksonville	Florida
United States	Research Site	Orange	California
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Rochester	New York
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Sandy	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Amgen	UCB Pharma

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Denmark,  Estonia,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Italy,  Latvia,  Lithuania,  Mexico,  New Zealand,  Norway,  Poland,  Romania,  Russian Federation,  Slovakia,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	52 weeks
Secondary	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.	Week 8 and weeks 12, 16, 20, 24, 36, and 52
Secondary	Number of Participants With Unplanned Revision Surgeries		52 weeks
Secondary	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.	52 weeks

External Links

•   AmgenTrials clinical trials website