E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine the efficacy of risedronate compared to placebo in children ≥ 4 to < 16 years of age with osteogenesis imperfecta (OI) as assessed by % change from Baseline in lumbar spine BMD at Month 12. |
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E.2.2 | Secondary objectives of the trial |
a) to evaluate the efficacy of risedronate compared to placebo in children ≥ 4 to < 16 year of age with OI as assessed by: • % change from Baseline in lumbar spine BMD at Month 6 • % change from Baseline in total body BMD • % change from Baseline in total body and lumbar spine BMC • change and % change from Baseline in total body and lumbar spine BMD Z score • % change from Baseline in lumbar spine and total body bone area • incidence and rate of new vertebral fractures • incidence and rate of clinical vertebral and non-vertebral fractures • percent change from Baseline in bone turnover markers • improvement from Baseline in musculoskeletal pain relief • improvement from Baseline in Quality of Life (QOL
b) to evaluate the safety and tolerability of risedronate treatment in children ≥ 4 to < 16 year of age with OI as assessed by: • adverse events • laboratory profiles including bone biopsy • change from Baseline in bone age • annualized growth velocity from Baseline |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
To be enrolled in this study, a child must meet the following: a) diagnosed with OI as based on a modified classification scale7,8 (Appendix 1) b) aged 4 through 15 years (≥ 4 to < 16), inclusive c) have an increased risk of fractures as defined by: • a history of at least 1 radiographically confirmed, non-traumatic or low impact fracture, plus low BMD (Z-score ≤ -1 at either total body or lumbar spine sites); or • very low BMD (Z-score ≤ -2.0 at either total body or lumbar spine sites) with or without a history of fractures d) have at least 2 evaluable lumbar spine vertebral bodies (L1-L4), namely without fracture or degenerative disease e) if female, post-menarche and sexually active, must be willing to agree to use a reliable contraceptive measure for the duration of the study. Acceptable forms of contraception include oral, injected or implanted contraceptives, or intrauterine devices. f) if female and post-menarche, must have a negative serum and urine pregnancy test at Screening g) able and willing to participate in the study as evidenced by a parent/legal guardian signing a valid written informed consent and the patient signing an assent (if appropriate). |
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E.4 | Principal exclusion criteria |
a) body weight < 10 kg b) history of cancer within the past 5 years c) untreated rickets within 1 year prior to enrollment d) history of clinically significant organic or psychiatric disease or findings on physical examination, which in the opinion of the Investigator, would prevent the patient from completing the study e) documented history of an abnormal or allergic reaction to bisphosphonates f) abuse of alcohol g) abuse of prescription or illicit drugs h) history of using any of the following medications, regardless of dose, for at least 1 month, within 3 months of enrollment: • anabolic agents • estrogen (except contraceptives) • progestogens (except contraceptives) • calcitriol, calcidiol, or alfacalcidol • calcitonin • fluoride (except dental health products) • glucocorticoids (does not include inhaled glucocorticoids) • growth hormones • parathyroid hormone (PTH) • strontium i) history of using any bisphosphonates within 1 year of enrollment, except for a single dose of oral bisphosphonate, such as risedronate or alendronate j) osteoporosis, secondary to diseases other than OI or drug therapies k) clinically significant abnormal laboratory finding at Screening, as follows: • liver function test (LFT), either AST or ALT > 2 x ULN • thyroid stimulating hormone (TSH) and PTH outside of the normal reference range Note: An iPTH level below the lower limit of the normal range may be associated with calcium supplementation. Therefore, the Investigator and the Medical Monitor will review the patient's personal data and medical history to confirm or refute that the low iPTH level is associated with high calcium supplementation • serum 25(OH) vitamin D < 20 nmol/L (8 ng/mL) • serum creatinine > 106 µmol/L (1.2 mg/dL) l) current use of anticonvulsant medication m) current use of anticoagulant medication n) participation in another clinical trial within 3 months of enrollment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percent change from Baseline in lumbar spine BMD at Month 12. |
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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 | Yes |
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
followed by open-label period |
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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 | Yes |
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 | Information not present in EudraCT |
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
|
Please refe to section 5.4 in the study protocol |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |