E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of osteoporosis in a paediatric (aged 5 to 17 years old) population treated with glucocorticoids (i.v. or oral) for chronic inflammatory conditions (including rheumatic conditions or inflammatoy bowel disease) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031282 |
E.1.2 | Term | Osteoporosis |
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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 |
Primary Efficacy objective: - Demonstrate that zoledronic acid administered every 6 months 0.05 mg/kg (max 5 mg) demonstrates superiority relative to placebo for the change in lumbar spine (LS) areal bone mineral density (BMD) Z-score at Month 12 relative to baseline. Safety objective: - Demonstrate that zoledronic acid is safe for the treatment of osteoporotic children treated with glucocorticoids for chronic inflammatory conditions through the monitoring of relevant clinical and laboratory safety parameters |
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E.2.2 | Secondary objectives of the trial |
- Evaluate between-treatment differences for the change in LS areal BMD Z-score at Month 6 relative to baseline - Evaluate between-treatment differences for the change from baseline in LS and total body BMC at 6 and 12 months - Evaluate between-treatment differences for the change in serum P1NP, NTX, BSAP & TRAP-5b at Months 6 and 12 relative to baseline - Evaluate between-treatment differences for the proportion of patients with new vertebral fractures at Month 12 relative to baseline - Evaluate between-treatment differences for change in vertebral morphometry 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 a chronic inflammatory condition, including rheumatic conditions or inflammatory bowel disease (IBD) - Treatment with systemic glucorticoids (i.v. or oral) within the 12 months preceding enrollment in the sudy (any duration) - Lumbar Spine areal BMD Z-score of -1.0 or worse and evidence of at least 1 vertebral compression fracture (at least Genant Grade 1 vertebral compression or radiographic signs of vertebral compression) confirmed by central reading - Ability to obtain informed consent/assent
Amendment: - Evidence of at least 1 vertebral compression fracture of Genant Grade 1 or higher or radiographic signs of vertebral fracture)within 1 month from Screening visit, confirmed by central reading. Radiographic signs of fracture include loss of endplate parallelism, vertebral buckling and endplate interruption.
AND/OR 1 or more, low-trauma, lower extremity long-bone fracture which occurred sometime within the 2 years PRECEDING, OR following the diagnosis of the underlying disease (rheumatologic condition/IBD), confirmed by central reading.
AND/ OR 2 or more, low-trauma, upper extremity long-bone fractures which occurred sometime within the 2 years PRECEDING, OR following the diagnosis of the underlying disease (rheumatologic condition/IBD), confirmed by central reading. |
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E.4 | Principal exclusion criteria |
- Any prior use of osteoporosis or bone-modifying therapy, such as bisphosphonates, sodium flouride, calcitonin, calcitriol, SERMs (Selective Estrogen-Receptor Modulators), LHRH agonists, Growth Hormone (GH) or medroxyprogesterone - Patients who have received testosterone or estrogen therapy may only be included in the trial if these therpies were given as part of physiological replacement in the setting of documented hormonal deficiencies - Any prior history of malignancy - Any medical condition that might interfere with the evaluation of LS BMD, such as severe scoliosis or spinal fusion. Patients with less than 3 evaluable vertebrae by DXA evaluation on the region of interest (ROI) L1-L4, as confirmed by the central imaging laboratory, will not be considered eligiblefor this study - Hypocalcemia and hypophosphatemia: any value (age-matched) below the normal range at screening - Vitamin D deficiency (serum 25-hydroxy vitamin D concentrations of <16 ng/ml or <40 nmol/L) at screening - Renal impairment defined as an estimated glomerular filtration rate (GFR)<35 ml/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 (44.2 µmol/L) - 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 cative 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 and (3) if sexually active, must be practicing a medically acceptable form of birth control for greater than 2 months prior to screenng visit. Females of childbearing 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 - History of primary bone disease (osteogenesis imperfecta, iodopathic juvenile osteoporosis, rickets/osteomalacia) - Non-ambulatory patients who require wheelchair assistance for mobility - History of Kawasaki's disease or Henoch-Schonlein Purpura |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to demonstrate that zoledronic acid administered every 6 months 0.05 mg/kg (max 5 mg) demonstrates superiority relative to placebo for the change in lumbar spine (LS) areal bone mineral density (BMD) Z-score at Month 12 relative to baseline. |
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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.8.3 |
The trial involves single site in the Member State concerned
| No |
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.8.6 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 | Information not present in EudraCT |
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 |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |