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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00799266




Registration number
NCT00799266
Ethics application status
Date submitted
26/11/2008
Date registered
27/11/2008
Date last updated
2/09/2020

Titles & IDs
Public title
An Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids
Scientific title
A Multicenter, Randomized, Double-blind, Placebo Controlled Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly Compared to Placebo in Osteoporotic Children Treated With Glucocorticoids.
Secondary ID [1] 0 0
2008-001252-52
Secondary ID [2] 0 0
CZOL446H2337
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Zoledronic acid
Treatment: Drugs - Placebo

Experimental: Zoledronic acid - Twice yearly 0.05 mg/kg (max 5 mg) i.v infusion (at least 30 minutes) of zoledronic acid

Placebo Comparator: Placebo - Twice yearly i.v of infusion of Placebo (similar dosing as active drug)


Treatment: Drugs: Zoledronic acid
intravenous infusion

Treatment: Drugs: Placebo
intravenous infusion

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

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 12 - Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 12. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition.
Timepoint [1] 0 0
Month 12
Secondary outcome [1] 0 0
Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 6 - Lumbar Spine Bone Mineral Density (BMD) Z-score was determined by the central imaging vendor before first treatment and at Month 6. The methods to be used to measure Lumbar Spine BMD Z-score were described in the respective DXA Manuals provided by central imaging vendor. Positive changes from baseline indicated an improvement in condition.
Timepoint [1] 0 0
Month 6
Secondary outcome [2] 0 0
Mean Change From Baseline in Lumbar Spine BMC at Month 6 and 12 - Lumbar Spine BMC was determined by the central imaging vendor before first treatment and at Months 6 and 12. The methods to be used to measure BMC were described in the respective DXA Manuals.
Timepoint [2] 0 0
Month 6, Month 12
Secondary outcome [3] 0 0
Mean Change From Baseline in Total Body BMC at Month 6 and 12 - Total body BMC was all determined by the central imaging vendor before first treatment and at Months 6 and 12. The methods to be used to measure BMC were described in the respective DXA Manuals.
Timepoint [3] 0 0
Month 6, Month 12
Secondary outcome [4] 0 0
Mean Change From Baseline in Serum P1NP at Months 6 and 12 - Serum Procollagen type 1 amino-terminal propeptide (P1NP) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.
Timepoint [4] 0 0
Month 6, Month 12
Secondary outcome [5] 0 0
Mean Change From Baseline in BSAP at Months 6 and 12 - Bone specific alkaline phosphatase (BSAP) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.
Timepoint [5] 0 0
Month 6, Month 12
Secondary outcome [6] 0 0
Mean Change From Baseline in Serum NTX at Months 6 and 12 - Serum Cross linked N-telopeptide (NTX) were collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.
Timepoint [6] 0 0
Month 6, Month 12
Secondary outcome [7] 0 0
Mean Change From Baseline in Serum TRAP-5b at Months 6 and 12 - Serum Tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) was collected before first treatment (baseline) and at Months 6 and Month 12 according to the instructions provided in the Laboratory Manual. The samples were analyzed in batches at the laboratory.
Timepoint [7] 0 0
Month 6, Month 12
Secondary outcome [8] 0 0
Number of Participants With New Vertebral Fractures at Month 12 - New vertebral fractures were defined as fractures of Genant Grade 1 or higher that occurred at lumbar or thoracic spine from first dose infusion to the end of the study.
Timepoint [8] 0 0
Month 12
Secondary outcome [9] 0 0
Mean Change From Baseline in Vertebral Morphometry at Month 12 - Vertebral morphometry (or concave index) was calculated using the average ratio between mid-height and posterior height from L1 to L4 and performed by a central reader.
Timepoint [9] 0 0
Month 12
Secondary outcome [10] 0 0
Percentage of Patients With Reduction in Pain at Months 3, 6, 9 and 12 - Pain was evaluated at each visit (in office and telephone visit) at randomization, Months 3, 6, 9 and 12 using the Faces Pain Scale-Revised (FPS-R). Children were selecting the face that best fits their pain. The pain score ranged from 0 (No Pain) to 10 (Very Much Pain). The reduction in pain from baseline by visit was evaluated based on whether or not patients had a decrease in their FPS-R from baseline. If pain remained the same or worsened from baseline a patient was classified as '0' and if the pain scale decreased then the patient was classified as '1'.
Timepoint [10] 0 0
Month 3, Month 6, Month 9 and Month 12
Secondary outcome [11] 0 0
Mean Change From Baseline in 2nd Metacarpal Cortical Width at Month 12 - Left posteroanterior (PA) hand/wrist X-ray were taken at Visit 1 and at the Month 12 visit to assess bone age and the between-treatment differences for change in 2nd metacarpal cortical width at Month 12 relative to baseline. If a fracture of the left upper extremity precluded radiographic imaging, then the right hand was evaluated for this purpose. In this case, the right hand was be imaged at both Visit 1 and at Month 12. The information was used in the assessment of bone density.
Timepoint [11] 0 0
Month 12
Secondary outcome [12] 0 0
Urinary Concentration of Zoledronic Acid at Month 12 - Urine was collected overnight or for at least 4 waking hours from all patients able to provide specimens, to measure urinary concentration of zoledronic acid at Month 12. Only descriptive analysis done.
Timepoint [12] 0 0
Month 12
Secondary outcome [13] 0 0
Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids - Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that zoledronic acid is safe for the treatment of osteoporotic children treated with glucocorticoids through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis done.
Timepoint [13] 0 0
Baseline through Month 12

Eligibility
Key inclusion criteria
Key

- A diagnosis of chronic rheumatologic conditions or inflammatory bowel disease or
Duchenne muscular dystrophy requiring systemic glucocorticoids (i.v. or oral) within
12 months prior to screening

- Lumbar Spine BMDZ-score of -0.5 or worse

- Evidence of at least at least 1 vertebral compression fracture of Genant Grade 1 or
higher (or radiographic signs of vertebral fracture) within 1 month from Screening
visit OR One or more, low-trauma, lower extremity long-bone fracture which occurred
sometime within the 2 years PRECEDING enrollment in the study OR Two or more,
low-trauma, upper extremity long-bone fractures which occurred sometime within the 2
years PRECEDING enrollment in the study

- Consent/assent to study participation

Key
Minimum age
5 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of primary bone disease (OI, Idiopathic Juvenile Osteoporosis,
Rickets/Osteomalacia)

- Any medical condition that might have interfered with the evaluation of lumbar spine
BMD, such as severe scoliosis or spinal fusion. Patients with less than 3 evaluable
vertebrae by Dual Energy X-ray Absorptiometry (DXA) evaluation in the region of
interest lumbar 1 (L1) to lumbar 4 (L4),

- Hypocalcemia and hypophosphatemia

- Serum 25-hydroxy vitamin D concentrations of <20 ng/mL or <50 nmol/L

- estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m2

- serum creatinine increase between Visit 1 and Visit 2 >0.5 mg/dL (44.2 µmol/L)

- Uncontrolled symptoms of cardiac failure or arrhythmia

- Any prior use of bisphosphonates, or high dose sodium fluoride

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 3
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)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
British Columbia
Country [2] 0 0
Canada
State/province [2] 0 0
Manitoba
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec
Country [5] 0 0
Hungary
State/province [5] 0 0
Budapest
Country [6] 0 0
Russian Federation
State/province [6] 0 0
Moscow
Country [7] 0 0
Russian Federation
State/province [7] 0 0
Saint Petersburg
Country [8] 0 0
South Africa
State/province [8] 0 0
Gauteng
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Birmingham
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study was designed to evaluate the efficacy and safety of zoledronic acid compared to
placebo in osteoporotic children treated with glucocorticoids
Trial website
https://clinicaltrials.gov/show/NCT00799266
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
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