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An Efficacy and Safety Trial of Intravenous Zoledronic Acid Twice Yearly in Osteoporotic Children Treated With Glucocorticoids

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ClinicalTrials.gov Identifier: NCT00799266
Recruitment Status : Completed
First Posted : November 27, 2008
Results First Posted : July 3, 2019
Last Update Posted : July 3, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Osteoporosis Drug: Zoledronic acid Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.
Actual Study Start Date : December 4, 2008
Actual Primary Completion Date : March 5, 2018
Actual Study Completion Date : March 5, 2018


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

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




Primary Outcome Measures :
  1. Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 12 [ Time Frame: 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.


Secondary Outcome Measures :
  1. Mean Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-score at Month 6 [ Time Frame: 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.

  2. Mean Change From Baseline in Lumbar Spine BMC at Month 6 and 12 [ Time Frame: Month 6, Month 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.

  3. Mean Change From Baseline in Total Body BMC at Month 6 and 12 [ Time Frame: Month 6, Month 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.

  4. Mean Change From Baseline in Serum P1NP at Months 6 and 12 [ Time Frame: Month 6, Month 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.

  5. Mean Change From Baseline in BSAP at Months 6 and 12 [ Time Frame: Month 6, Month 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.

  6. Mean Change From Baseline in Serum NTX at Months 6 and 12 [ Time Frame: Month 6, Month 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.

  7. Mean Change From Baseline in Serum TRAP-5b at Months 6 and 12 [ Time Frame: Month 6, Month 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.

  8. Number of Participants With New Vertebral Fractures at Month 12 [ Time Frame: 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.

  9. Mean Change From Baseline in Vertebral Morphometry at Month 12 [ Time Frame: 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.

  10. Percentage of Patients With Reduction in Pain at Months 3, 6, 9 and 12 [ Time Frame: Month 3, Month 6, Month 9 and Month 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'.

  11. Mean Change From Baseline in 2nd Metacarpal Cortical Width at Month 12 [ Time Frame: 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.

  12. Urinary Concentration of Zoledronic Acid at Month 12 [ Time Frame: 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.

  13. Safety of Zoledronic Acid for the Treatment of Osteoporotic Children Treated With Glucocorticoids [ Time Frame: Baseline through Month 12 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00799266


Locations
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Australia, New South Wales
Novartis Investigative Site
Westmead, New South Wales, Australia, 2145
Canada, British Columbia
Novartis Investigative Site
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
Novartis Investigative Site
Winnipeg, Manitoba, Canada, R3E 0Z2
Canada, Ontario
Novartis Investigative Site
Ottawa, Ontario, Canada, K1H 8L1
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3H 1P3
Novartis Investigative Site
Montreal, Quebec, Canada, H3T 1C5
Hungary
Novartis Investigative Site
Budapest, Hungary, 1085
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation, 119991
Novartis Investigative Site
Saint Petersburg, Russian Federation, 195067
South Africa
Novartis Investigative Site
Soweto, Gauteng, South Africa, 2013
United Kingdom
Novartis Investigative Site
Birmingham, West Midlands, United Kingdom, B4 6NH
Novartis Investigative Site
Manchester, United Kingdom, M14 0JH
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] October 26, 2015
Statistical Analysis Plan  [PDF] August 21, 2017


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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00799266     History of Changes
Other Study ID Numbers: CZOL446H2337
2008-001252-52 ( EudraCT Number )
First Posted: November 27, 2008    Key Record Dates
Results First Posted: July 3, 2019
Last Update Posted: July 3, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.


Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Osteoporosis, children and adolescents, zoledronic acid, chronic inflammation, Duchenne muscular dystrophy, glucocorticoids, chronic inflammatory conditions

Additional relevant MeSH terms:
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Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Zoledronic Acid
Glucocorticoids
Bone Density Conservation Agents
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists