Clinical trial NCT00799266: An Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids
Official 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis
Keywords: Osteoporosis, children and adolescents, zoledronic acid, chronic inflammation, Duchenne muscular dystrophy, glucocorticoids, chronic inflammatory conditions
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-11-27
Enrollment: 34
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed to evaluate the efficacy and safety of zoledronic acid compared to placebo in osteoporotic children treated with glucocorticoids

Detailed description: In March 2017, Novartis stopped enrollment as the study was not feasible to be conducted due to low enrollment and other recruitment challenges. Patients receiving the treatment continued to receive the treatment per protocol.

Eligibility criteria: Key Inclusion Criteria:

* 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 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

Primary outcomes:
measure: Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 12
timeFrame: Month 12
Secondary outcomes:
measure: Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 6
timeFrame: Month 6
measure: Mean Change From Baseline in Lumbar Spine BMC at Month 6 and 12
timeFrame: Month 6, Month 12
measure: Mean Change From Baseline in Total Body BMC at Month 6 and 12
timeFrame: Month 6, Month 12
measure: Mean Change From Baseline in Serum P1NP at Months 6 and 12
timeFrame: Month 6, Month 12
measure: Mean Change From Baseline in BSAP at Months 6 and 12
timeFrame: Month 6, Month 12
measure: Mean Change From Baseline in Serum NTX at Months 6 and 12
timeFrame: Month 6, Month 12
measure: Mean Change From Baseline in Serum TRAP-5b at Months 6 and 12
timeFrame: Month 6, Month 12
measure: Number of Participants With New Vertebral Fractures at Month 12
timeFrame: Month 12
measure: Mean Change From Baseline in Vertebral Morphometry at Month 12
timeFrame: Month 12
measure: Percentage of Patients With Reduction in Pain at Months 3, 6, 9 and 12
timeFrame: Month 3, Month 6, Month 9 and Month 12
measure: Mean Change From Baseline in 2nd Metacarpal Cortical Width at Month 12
timeFrame: Month 12
measure: Urinary Concentration of Zoledronic Acid at Month 12
timeFrame: Month 12
measure: Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids
timeFrame: Baseline through Month 12
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Novartis Investigative Site
state: Manitoba
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Soweto
country: South Africa
facility: Novartis Investigative Site
state: Gauteng
city: West Midlands
country: United Kingdom
facility: Novartis Investigative Site
state: Birmingham
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Ward LM, Choudhury A, Alos N, Cabral DA, Rodd C, Sbrocchi AM, Taback S, Padidela R, Shaw NJ, Hosszu E, Kostik M, Alexeeva E, Thandrayen K, Shenouda N, Jaremko JL, Sunkara G, Sayyed S, Aftring RP, Munns CF. Zoledronic Acid vs Placebo in Pediatric Glucocorticoid-induced Osteoporosis: A Randomized, Double-blind, Phase 3 Trial. J Clin Endocrinol Metab. 2021 Nov 19;106(12):e5222-e5235. doi: 10.1210/clinem/dgab458.