E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of osteoporosis in a paediatric population (aged 5 to 17 years old) treated with systemic glucocorticoids (i.v. or oral) |
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E.1.1.1 | Medical condition in easily understood language |
Disease of bones that leads to an increase risk of fracture |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10028395 |
E.1.2 | Term | Musculoskeletal and connective tissue disorders |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
▪ To evaluate between-treatment differences for the change in LS areal BMD Z-score at Month 6 relative to baseline
▪ To evaluate between-treatment differences for the change from baseline in LS and total body BMC at 6 and 12 months
▪ To evaluate between-treatment differences for the change in serum P1NP, NTX, BSAP & TRAP-5b at Months 6 and 12 relative to baseline
▪ To evaluate between-treatment differences for the proportion of patients with new vertebral fractures at Month 12 relative to baseline
▪ To evaluate the between-treatment differences for change in vertebral morphometry at Month 12 relative to baseline
▪ To evaluate the between-treatment differences for change in pain using the Faces Pain Scale-Revised (FPS-R) at months 3 6, 9 and 12 relative to baseline
▪ To evaluate the between-treatment differences for change in 2nd metacarpal cortical width at month 12 relative to baseline. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
▪ 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
▪ Willingness to consent/assent to study participation
Other protocol-defined inclusion criteria may apply |
|
E.4 | Principal exclusion criteria |
▪ Any prior use bisphosphonates, sodium fluoride
▪ History of malignancy
▪ History of primary bone disease (osteogenesis imperfecta, idiopathic juvenile osteoporosis, rickets/osteomalacia).
▪ Any medical condition that might interfere with the evaluation of LS BMD, such as severe scoliosis or spinal fusion
▪ Hypocalcemia and hypophosphatemia: any value (age-matched) below the normal range at screening
▪ Vitamin D deficiency (serum 25-hydroxy vitamin D concentrations of < 16ng/mL or < 40 nmol/L) at screening
▪ Renal impairment defined as an estimated glomerular filtration rate (GFR) < 35ml/min/1.73 m2 at screening based on the Schwartz formula
▪ A serum creatinine increase between Visit 1 and Visit 2 greater than 0.5 mg/dL (44.2mmol/L)
▪ Duchenne Muscular Dystrophy patients with history of serious renal disease
▪ Duchenne Muscular Dystrophy patients with history of symptomatic cardiac involvement
▪ History of hyperparathyroidism or hyperthyroidism within 1 year of screening
▪ History of hypothyroidism unless on a stable treatment regimen for > 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.
▪ History of primary bone disease (osteogenesis imperfecta, idiopathic juvenile osteoporosis, rickets/osteomalacia)
Other protocol-defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
LS areal BMD Z-score measurement.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At screening and month 12.
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E.5.2 | 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. |
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E.5.2.1 | 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). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Brazil |
Canada |
Finland |
Germany |
Hungary |
Italy |
New Zealand |
Poland |
Romania |
Russian Federation |
South Africa |
Sweden |
Turkey |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |