Osteogenesis Imperfecta MedDRA version: 20.0 Level: PT Classification code 10031243 Term: Osteogenesis imperfecta System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Amgen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Informed consent (to be provided by parent or legal guardian) and informed assent (to be provided by subjects when age-appropriate). - Children aged 2 to 17 years inclusive at screening - Clinical diagnosis of OI defined as a clinical history consistent with type I-IV OI as determined by presence of expected phenotype (examples include: facial shape, voice, blue sclera, dentinogenesis imperfecta, typical radiographic features, fracture pattern) and lack of additional features unrelated to type I-IV OI (eg, blindness, mental retardation, neuropathy, craniosynostosis; premature exfoliation of deciduous teeth) ?* If familial, also must be autosomal dominant - Clinical severity of OI as defined by o 2 or more prevalent vertebral compression fractures; OR o 1 prevalent vertebral compression fracture and 1 or more nonvertebral fractures within the previous 2 years; OR o 3 or more fractures within the previous 2 years Are the trial subjects under 18? yes Number of subjects for this age range: 150 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: Subjects meeting any of the following criteria at screening are not eligible for enrollment: - Inability or unwillingness to comply with the requirements for frequent calcium and phosphorus monitoring for 14 days after the first dose of denosumab (only applies to the first 5 subjects age 11 to17 enrolled in the study and the first 5 subjects of any age meeting the criteria for increased bone turnover (see Section 2.3.2.1) - Currently unhealed fracture or osteotomy as defined by orthopedic opinion - Osteotomy within 5 months of screening - Evidence of untreated oral cavities or oral infections - Recent or planned invasive dental procedure - Surgical tooth extraction which has not healed by screening - History of an electrophoresis pattern inconsistent with type I to IV OI - History of known mutation in a gene other than COL1A1/COL1A2 causing OI or metabolic bone disease - Abnormalities of the following per central laboratory reference ranges at screening: o Serum albumin corrected calcium 1.5 x upper limit of normal (ULN) o Total bilirubin (TBL) > 1.5 x ULN (subjects with Gilbert syndrome are eligible) o Serum phosphorus 20% above the ULN or > 20% below the LLN - Estimated glomerular filtration rate (eGFR) 10% ULN) o Current metaphyseal index Z-score > +1 o History of osteomalacia or rickets (chart review) o Other bone diseases that affect bone metabolism (eg, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis, hypophosphatasia) o History of autoimmune disease o History of malabsorption (in children with serum albumin < LLN, malabsorption should be clinically ruled out by the PI to confirm eligibility) o History of rare hereditary problems of fructose intolerance o History of long QT syndrome o History of non-healing osteotomy o History of malignancy o History of alcohol or drug abuse o History of any solid organ or bone marrow transplant o Contraindicated or poorly tolerant of denosumab therapy - Positive blood screen for human immunodeficiency virus -1 or -2 antobody - Positive blood screen for hepatitis B surface antigen or hepatitis C antibody - Known to have tested positive for human immunodeficiency virus - Known hepatic disease or evidence of acute or chronic hepatitis B or hepatitis C - Currently pregnant or planning a pregnancy during the study and for an additional 5 months after the last dose of denosumab - For sexually active girls: refusal to use highly effective methods of contraception and to continue this practice for 5 months after the last injection of denosumab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of denosumab on lumbar spine bone mineral density (BMD) Z-score at 12 months, as assessed by dual-energy X-ray absorptiometry (DXA), in children 2 to 17 years of age with osteogenesis imperfecta (OI).;Secondary Objective: To evaluate denosumab in children 2 to 17 years of age with OI with respect to: - Change in lumbar spine BMD Z-score, as assessed by DXA, at 6, 18, 24, and 36 months - Change in proximal femur BMD Z-score, as assessed by DXA, at 6, 12, 18, 24, and 36 months (in subjects 5 years of age and older) - Incidence of x-ray confirmed long bone and new and worsening vertebral fractures from pre-treatment to post-treatment at 12, 24, and 36 months - Incidence of improving vertebral fractures from pre-treatment to post-treatment at 12, 24, and 36 months (overall, among subjects with clinical fracture reduction, and among subjects with clinical fracture increase) - Incidence of pre-treatment compared with post-treatment vertebral and nonvertebral fractures at 12, 24, and 36 months + Exploratory and Safety objectives For complete list, please refer to the protocol;Primary end point(s): Change from baseline in lumbar spine BMD Z-score, as assessed by DXA, at 12 months.;Timepoint(s) of evaluation of this end point: at 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in lumbar spine BMD Z-score, as assessed by DXA, at 6, 18, 24, and 36 months - Change from baseline in proximal femur BMD Z-score, as assessed by DXA, at 6, 12, 18, 24, and 36 months (in subjects 5 years of age and older) - Subject incidence of x-ray confirmed long bone fractures and new and worsening vertebral fractures at 12, 24, and 36 months compared to pre-treatment - Subject incidence of improved vertebral fractures at 12, 24, and 36 months compared to pre-treatment (overall, among subjects with clinical fracture reduction and among subjects with clinical fracture increase) - Subject incidence of vertebral and nonvertebral fractures at 12, 24, and 36 months compared to pre-treatment - Change from baseline in CHQ-PF-50 Physical Summary score at 12, 24, and 36 months - Change from baseline in CHQ-PF-50 Psychological Summary score at 12, 24, and 36 months - Change from baseline in CHAQ Disability Index score at 12, 24, and 36 months - Change from baseline in WBFPRS at 12, 24, and 36 months - Change from baseline in growth velocity (determined by calculating age-adjusted Z-scores for height, weight and BMI) at 36 months - Serum concentration of denosumab at 1 and 10 days, and 6, 12, 18, 24, 30, and 36 months - Serum concentration of denosumab at 1, 10, and 30 days, and 3, 6, 12, 18, 24, 30, and 36 months (PK/BTM substudy only);Timepoint(s) of evaluation of this end point: see list above | — |
Countries
Australia, Belgium, Bulgaria, Canada, Czech Republic, Finland, France, Germany, Hungary, Poland, Spain, United Kingdom, United States
Contacts
Public ContactIHQ-Medical Info - Clinical Trials
Amgen (Europe) GmbH
Outcome results
None listed