Treatment of osteoporosis in a paediatric population (aged 5 to 17 years old) treated with systemic glucocorticoids (i.v. or oral) MedDRA version: 18.1 Level: SOC Classification code 10028395 Term: Musculoskeletal and connective tissue disorders System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Aclasta®
Product Name: Aclasta®
Product Code: ZOL446
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ZOLEDRONIC ACID
CAS Number: 118072-93-8
Current Sponsor code: ZOL446
Co
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Written informed consent must be obtained before any assessment is performed. An assent needs to be provided in accordance with ICH and local regulations. ? Children, male or female, between 5 and 17 years of age at visit 1 of the study ? Confirmed diagnosis of non-malignant conditions requiring treatment with systemic glucocorticoids receiving systemic glucocorticoids (i.v. or oral) within the 12 months preceding enrollment in the study (any duration) ? Lumbar Spine areal BMD Z-score of -0.5 or worse ? Evidence of at least 1 vertebral compression fracture (at least Genant Grade 1 vertebral compression or radiographic signs of vertebral compression*) seen in X-ray and asymptomatic within 1 month of or at screening visit confirmed by central reading OR One or more, low-trauma, lower extremity long-bone fracture which occurred sometime within the 2 years preceding enrollment in the study, confirmed by central reading or radiological report. OR Two or more, low-trauma, upper extremity long-bone fractures which occurred sometime within the 2 years preceding enrollment in the study, confirmed by central reading or radiological report. Low trauma fracture is defined as falling from standing height or less Other protocol-defined inclusion criteria may apply Are the trial subjects under 18? yes Number of subjects for this age range: 92 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients/ subjects fulfilling any of the following criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients. ? History of primary bone disease (osteogenesis imperfecta, idiopathic juvenile osteoporosis, rickets/osteomalacia) ? Any prior use bisphosphonates, or high dose sodium fluoride (i.e. dental use is permitted) ? Any medical condition that might interfere with the evaluation of LS BMD, such as severe scoliosis or spinal fusion ? As per Investigator's judgment, patient is anticipated to have surgery within subsequent year. ? Hypocalcemia and hypophosphatemia: any value (age-matched) below the normal range at screening ? Serum 25-hydroxy Vitamin D concentrations of 6 months, with at least one documented normal TSH and FT4 levels during this 6 month period ? History of sarcoidosis ? Diagnosis of active uveitis (symptomatic or asymptomatic) at the time of enrollment of the study ? Female patients of child bearing potential are eligible only if they are: (1) not pregnant/ non-lactating; (2) are sexually abstinent or are surgically sterile (3) if sexually active, must be practicing a medically acceptable form of birth control for greater than 2 months prior to screening visit. Females of child bearing potential who are sexually active must agree to continue to practice their birth control during the trial and at least 1 year after completing the trial and must consent to a pregnancy test prior to every dose administration and at the End of Study (EOS) Visit. FOR sites and/ or regions where additional safeguards are required e.g. UK, Italy, Germany, Sweden & etc.: Female patients of child bearing potential are eligible only if they are not pregnant/non-lactating. Females of child bearing potential must be practicing a medically acceptable form of birth control for greater than 2 months prior to screening visit. At least one and preferable two complementary forms of contraception including a barrier method should be used and be continued throughout the trial and for at least 1 year after completing the trial. They must also consent to a pregnancy test prior to every dose administration and at the EOS visit. An additional supervised urine pregnancy test will be assessed at week 12 ? History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy objective: The primary efficacy objective of the study is to demonstrate that zoledronic acid administered every 6 months 0.05 mg/kg (max 5 mg) is superior to placebo for the change in lumbar spine (LS) areal bone mineral density (BMD) Z-score at Month 12 relative to baseline. The safety objectives are: - 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 - to measure urinary concentration of zoledronic acid at Month 12;Secondary Objective: ? To evaluate between-treatment differences for the change in LS areal BMD Z-score ? To evaluate between-treatment differences for the change from baseline in LS and total body BMC ? To evaluate between-treatment differences for the change in serum P1NP, NTX, BSAP & TRAP-5b ? To evaluate between-treatment differences for the proportion of patients with new vertebral fractures ? To evaluate the between-treatment differences for change in vertebral morphometry ? To evaluate the between-treatment differences for change in pain using the Faces Pain Scale-Revised (FPS-R) ? To evaluate the between-treatment differences for change in 2nd metacarpal cortical width ? To measure urinary concentration of zoledronic acid ? The safety objective is 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.;Primary end point(s): LS areal BMD Z-score measurement. ;Timepoint(s) of evaluation of this end point: At screening and month 12. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy assessments: a. LS areal BMD Z-score. b. LS and total body BMC. c. Serum P1NP and BSAP. d. Serum NTx and TRAP5b. e. new vertebral fractures based on a lateral thoracolumbar spine x-ray. f. vertebral morphometry, based on a lateral thoracolumbar spine x-ray. g. Pain using the Faces Pain Scale-Revised (FPS-R). h. Metacarpal cortical width. i. measurement of urinary concentration;Timepoint(s) of evaluation of this end point: Secondary efficacy assessments: a. at Month 6 (visit 5). b. at 6 and 12 months (visits 5 and 8/EOS). c. at months 6 and 12 (visits 5 and 8/EOS). d. at months 6 and 12 (visits 5 and 8/EOS). e. at month 12 relative to baseline (visit 8/EOS). f. at month 12 relative to baseline (visit 8/EOS). g. at months 3, 6, 9 and 12 relative to baseline (visits 4,5,7 and 8/EOS). h. at month 12 relative to baseline (visit 8/EOS). i. at Month 12 (Visit 8) | — |
Countries
Australia, Belgium, Brazil, Canada, Finland, Germany, Hungary, Italy, New Zealand, Poland, Romania, Russian Federation, South Africa, Sweden, Turkey, Ukraine, United Kingdom
Contacts
Public ContactMedical Information Services
Novartis Pharmaceuticals UK Limited
Outcome results
None listed