The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12614000578606
Ethics application status
Approved
Date submitted
23/05/2014
Date registered
29/05/2014
Date last updated
24/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Effects of Denosumab (study medication) versus Placebo (Dummy medication) on Bone Density in People who have had a Spinal Cord Injury
Scientific title
A Prospective, Randomised, Double Blind, Placebo Controlled Study To Compare The Safety And Efficacy(Percentage change from baseline in bone mineral density at the total hip at 12 months, compared with placebo) Of Subcutaneous Denosumab 60mg 6 monthly In Acute Spinal Cord Injury In Males And Females.
Secondary ID [1] 284639 0
Nil
Universal Trial Number (UTN)
U1111-1157-2315
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal Cord Injury 291955 0
Bone loss 292008 0
Condition category
Condition code
Injuries and Accidents 292306 292306 0 0
Fractures
Musculoskeletal 292349 292349 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Denosumab 60 mg subcutaneous injection 6 monthly - arm 1

Matched placebo - arm 2
At the end of year one both arms can receive open label denosumab 60mg by subcutaneous injection for the second year of the study. Blinded injections at baseline and 6 months. Open label denosumab at 12 and 18 months.
Intervention code [1] 289432 0
Treatment: Drugs
Comparator / control treatment
Placebo- saline injection
Control group
Placebo

Outcomes
Primary outcome [1] 292179 0
Percentage change from baseline in bone mineral density at the total hip at 12 months, compared with placebo.
Bone mineral density measured by iDXA - dual energy x-ray absorptiometry
Timepoint [1] 292179 0
12 months
Secondary outcome [1] 308377 0
Percentage change from baseline in bone mineral density (BMD) at the lumbar spine, femoral neck, trochanter, femoral shaft, total body (head included), and distal 1/3 radius at 12 months compared with placebo. Bone mineral density measured by dual energy x-ray absorptiometry (iDXA)
Timepoint [1] 308377 0
12 months
Secondary outcome [2] 308378 0
Percentage change from baseline in regional bone mineral density (BMD) (arms, legs, trunk, pelvis,) at 12 months compared with placebo. Bone mineral density measured by dual energy x-ray absorptiometry (iDXA)
Timepoint [2] 308378 0
12 months

Eligibility
Key inclusion criteria
1. Traumatic Spinal Cord Injury, Male or Female
2. Aged 25-60 years. Skeletally mature males and females
3. Within a minimum of 7 and a maximum of 10 days of injury unless participant has to wait for fracture fixation, in which case this may be extended.
4. Women of childbearing potential must be using 2 highly effective methods of birth control and to continue this practice for 7 months after last injection of study medication.
5. Participant has provided informed consent prior to any study specific procedures.
Minimum age
25 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinically significant indications of heterogeneous ossification.
2. History of osteonecrosis of the jaw and/or recent tooth extraction or dental surgery.
3. History of solid organ or bone marrow transplant.
4. Inability to tolerate DXA measurement.
5. On other treatment affecting bone turnover including the use of zoledronic acid or other bishphospohates within the year preceding study entry.
6. Serum 25-OH D <12 ng/ml
7. History of renal calculi
8. Patient is in the opinion of the investigator mentally or legally incapacitated and unable to give informed consent.
9. Significant malabsorption including Coeliac Disease, Short Bowel Syndrome, Crohn’s Disease, Previous Gastric Bypass.
10. Participation in another clinical trial
11. Active cancer and/or malignancy in last 5 years (except cervical carcinoma in situ or basal cell carcinoma)
12. Metabolic bone disease including hyperparathyroidism, hypo or hypercalcaemia, Paget’s disease, osteomalacia or osteogenesis imperfecta.
13. History of hypersensitivity or intolerance to the active substance- to CHO derived Proteins
14. Known intolerance to calcium supplements
15. Severely ill patients defined as:
a. Respiratory failure/ Ventilator dependency
b. Acute renal failure
c. Presence of severe infection
d. Multiple fractures affecting ability to rehabilitate
16. Pregnancy and/or currently lactating
17. T-score of -2.5 or lower on BMD at total hip or lumbar spine
18. Documented hypocalcaemia- a value of <2.1 (corrected calcium)mmol/L
19. eGFR <30ml/minute
20. Elevated transaminases more than or equal to 2.0 x upper limit of normal (ULN); Elevated total bilirubin (TBL) > 1.5 x ULN
21. Any condition or illness (acute, chronic, or history), which in the opinion of the Investigator might interfere with the evaluation of efficacy and safety during the study or may otherwise compromise the safety of the subject
22. Currently enrolled in or has not yet completed at least 1 month since ending another trial

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)
Enrolled subjects after screening wil be give the next number kit of medication - 01,02 etc. First kit labelled A ( given at study entry)and 2nd labelled B ( given at 6 month visit).
For the second year open label medication is provided.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be undertaken using a randomisation schedule prepared in advance by the independent statistician and will be arranged in permuted blocks. The Statistician who will provide a randomisation schedule to the provider of the study medication who will then provide numbered medication kits to the study site with the medication identified as Denosumab/Placebo
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The primary outcome the percentage change in total hip BMD from baseline to 12 months will be compared between randomised arms using one-way ANCOVA. The percentage change is defined as the change from baseline divided by the baseline level, times 100. The baseline level will be used as the covariate in this analysis. The primary analysis will utilise the intention to treat population which includes all participants who are randomised and receive a least one dose of study medication treatment. Any participants who do not have a 12 month assessment of BMD for any reason will have the baseline observation carried forward and this will be used as the 12 month level. There will be no imputation of missing data. This approach provides a conservative estimate of the change and the impact of this procedure and the robustness of the results will be tested by a sensitivity analysis which will only include those participants who have a 12 month assessment and have had all protocol defined procedures undertaken, i.e. the per-protocol population.
All secondary and exploratory outcomes will be analysed using the same process as the primary outcome analysis, with baseline levels as covariates and using, in the first instance the intention-to-treat population. Statistical significance is defined when the two-sided p-value is <0.05.
As the sample size is small there will be no sub-group analysis. The power calculation requires 16 patients per group to be evaluated to provide at least 80% power at the two tailed 5% significance level to show a difference in the percent change in total hip BMD over 12 months of 2.5% or more. .Allowing for 20% loss to follow-up or withdrawal it is intended to recruit 20 patients per group.
A pooled standard deviation of 2.5% was used for this estimate.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
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 outside Australia
Country [1] 6068 0
New Zealand
State/province [1] 6068 0
Canterbury

Funding & Sponsors
Funding source category [1] 289273 0
Charities/Societies/Foundations
Name [1] 289273 0
CGM Research Trust
Address [1] 289273 0
c/- The Princess Margaret Hospital
Casmere Road
Christchurch 8022
Country [1] 289273 0
New Zealand
Funding source category [2] 289274 0
Commercial sector/Industry
Name [2] 289274 0
Amgen Australia
Address [2] 289274 0
Amgen Australia Pty Ltd Mezzanine Level 115 Cotham Road Kew, Victoria, 3101

Country [2] 289274 0
Australia
Primary sponsor type
Other
Name
CGM Research Trust
Address
c/- The Princess Margaret Hospital
Cashmere Road
Christchurch 8022
Country
New Zealand
Secondary sponsor category [1] 287947 0
None
Name [1] 287947 0
Address [1] 287947 0
Country [1] 287947 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291044 0
New Zealand Health and Disability Ethics Committee
Ethics committee address [1] 291044 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 291044 0
New Zealand
Date submitted for ethics approval [1] 291044 0
16/01/2012
Approval date [1] 291044 0
27/02/2012
Ethics approval number [1] 291044 0
URB/12/02/003

Summary
Brief summary
Participants in this study will have recently suffered a spinal cord injury. The study is using a medication to try to prevent the bone loss that occurs in people who have had this type of injury. This bone loss predisposes people to the risk of fracture. It is a twelve month study of blinded medication followed by 12 months of open label medication – 24 months in total. Study visits occur at baseline, month 3 month 6 month 12 month 18 and month 24.The study is comparing the study medication (Denosumab) to placebo (dummy medicine)in the first year. In the second year of the study all participants will receive active study medication. The medication is given by an injection under the skin once every 6 months. Participants in this study will have blood testing, measurement of bone density and renal ultrasound measurements.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48582 0
Dr Nigel Gilchrist
Address 48582 0
CGM Research Trust
c/- The Princess Margaret Hospital
PO Box 731, Cashmere Road
Christchurch 8022
Country 48582 0
New Zealand
Phone 48582 0
64 3 3377820
Fax 48582 0
64 3 3377991
Email 48582 0
enquiries@gm-research.org.nz
Contact person for public queries
Name 48583 0
Ms Rachel March RN
Address 48583 0
CGM Research Trust
c/- The Princess margaret Hospital
PO Box 731, Cashmere Road
Christchurch 8022
Country 48583 0
New Zealand
Phone 48583 0
64 3 3377752
Fax 48583 0
64 3 3377991
Email 48583 0
rachel.march@gm-research.org.nz
Contact person for scientific queries
Name 48584 0
Dr Nigel Gilchrist
Address 48584 0
CGM Research Trust
c/- The Princess Margaret Hospital
PO Box 731, Cashmere Road
Christchurch 8022
Country 48584 0
New Zealand
Phone 48584 0
64 3 3377820
Fax 48584 0
64 3 3377991
Email 48584 0
enquiries@gm-research.org.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary