E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteogenesis Imperfecta (OI) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031243 |
E.1.2 | Term | Osteogenesis imperfecta |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
-To evaluate long-term safety of denosumab in subjects with pediatric OI completing Study 20130173 |
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E.2.2 | Secondary objectives of the trial |
-To describe changes in bone mineral density (BMD) of lumbar spine and proximal femur (total hip and femoral neck) from baseline to 12 and 24 months -To describe the incidence of X-ray confirmed long bone and new and worsening vertebral fractures from baseline to 12 and 24 months -To describe the incidence of vertebral and non-vertebral fractures from baseline to 12 months and 24 months -To describe the change in growth velocity (determined by calculating age-adjusted Z-scores for height, weight, and body mass index [BMI]) at 12 and 24 months |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects are eligible to be included in the study only if all of the following criteria apply: -Subject has provided informed consent/assent prior to initiation of any Study 20170534 specific activities/procedures. Subject’s legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated. -Subject was enrolled in Study 20130173 and completed the month 36 visit (regardless of completing or ending investigational product early).
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E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following criteria apply: Prior/Concomitant Therapy -Treatment with any prohibited proscribed medications during Study 20130173 while receiving denosumab. Eligibility into study treatment with alternative osteoporosis medication/s of investigator's choice, follow guidelines per the specific alternative osteoporosis medication/s selected. For subjects off-treatment (observation only), no prohibited medications apply. Prior/Concurrent Clinical Study Experience -Subjects currently receiving treatment in another investigational device or drug study other than Study 20130173. Other investigational procedures while participating in this study are excluded. Other Exclusions -For subjects expected to receive investigational product (denosumab) at study day 1: -Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 5 months after the last dose of denosumab. Females of childbearing potential (Tanner Stage ≥ 2) should only be included in the study after a negative highly sensitive urine or serum pregnancy test. For study treatment with alternative osteoporosis medication/s of investigator's choice, follow guidelines per the specific alternative osteoporosis medication/s selected. For subjects off-treatment (observation only), no exclusion applies. -For subjects expected to receive investigational product (denosumab) at study day 1: -Female subjects of childbearing potential unwilling to practice true sexual abstinence (refrain from heterosexual intercourse) or use 1 highly effective method of contraception during treatment and for an additional 5 months after the last dose of investigational product (IP) (denosumab). For study treatment with alternative osteoporosis medication/s of investigator’s choice, follow contraception guidelines per the specific alternative osteoporosis medication/s selected. For subjects not receiving any IP (observation only), no contraception required. -History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
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E.5 End points |
E.5.1 | Primary end point(s) |
-The primary endpoint is safety monitoring, including subject incidence of adverse events, serious adverse events and adverse events of special interest, subject prevalence of immunogenicity, changes from baseline in laboratory values and vital signs, and subject incidence of metaphyseal index Z score above age-appropriate normal range, abnormal molar eruption, and mandibular shaping |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
-Actual values and changes in BMD-Z score of lumbar spine and proximal femur (total hip and femoral neck) from baseline and from Study 20130173 baseline, as assessed by dual X-ray absorptometry (DXA), to 12 and 24 months -Subject incidence of X-ray confirmed long bone and new and worsening vertebral fractures from baseline and from Study 20130173 baseline to 12 and 24 months -Subject incidence of vertebral and non-vertebral fractures from baseline and from Study 20130173 baseline to 12 and 24 months -Change from baseline and from Study 20130173 baseline in growth velocity (determined by calculating age-adjusted Z-scores for height, weight, and BMI) at 12 and 24 months |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
Bulgaria |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Italy |
Poland |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end of study date is defined as the date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie, last subject last visit), following any additional parts in the study (eg, long-term follow-up), as applicable. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 5 |