Osteogenesis imperfecta (OI) is a group of genetic skeletal disorders characterized by increased bone fragility, low bone mass , and increased bone turnover contributing to osteoporosis, fractures, and other conditions. OI is the most common form of primary osteoporosis in children with an estimated incidence of 1 per 25,000 live births. MedDRA version: 20.0 Level: PT Classification code 10031243 Term: Osteogenesis imperfecta System Organ Class: 10010331 - Congenital, familial and genetic d
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject's legally acceptable representative has provided informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to initiation of any study-specific activities/procedures Ambulatory male or female children 5 to less than 12 years of age (cohorts 2,4, and 6) or adolescents 12 to less than 18 years of age (cohorts 1, 3 and 5) upon entry into screening Clinical diagnosis of OI defined as a clinical history consistent with type I-IV OI as determined by presence of expected phenotype (eg, 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 Are the trial subjects under 18? yes Number of subjects for this age range: 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: History of an electrophoresis pattern inconsistent with type I to type IV OI History of known mutation in a gene other than collagen type I alpha/collagen type I alpha 2 (COL1AI/COL1A2) causing OI or other metabolic bone disease History of congenital dislocation of the radial head, interosseous membrane calcification, or exuberant callus formation History of osteomalacia or rickets Body weight less than 10 kg or greater than 90 kg History of other bone diseases that affect bone metabolism (eg, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis, hypophosphatasia) History of Kawasaki disease, rheumatic myocarditis, ischemic cardiomyopathy, inherited cardiomyopathies, valvular heart disease, nephrotic syndrome, familial hypercholesterolemia, stroke, or any thromboembolic disorder Evidence of untreated or unhealed oral cavities or oral infections Unhealed or planned invasive dental or tooth procedure; removal of baby teeth is acceptable and not considered an invasive dental procedure Unhealed fracture as defined by orthopedic opinion Osteotomy, rodding surgery or spinal fusion surgery within 5 months prior to screening, or not yet healed per orthopedic surgeon Any planned major surgery, including skeletal surgery (eg, rodding surgery, spinal surgery) within the next 6 months from Day 1 that would interfere with study procedures or would require missing of any IP Symptoms associated with skull abnormalities such as basilar invagination, basilar impression or Chiari malformation (headache induced by coughing or straining for stool, or parasthesia or weakness) History of malabsorption (in children with serum albumin 6 months and has supporting laboratory documentation within 6 months prior to or at screening indicating normal serum thyroidstimulating hormone [TSH] value Evidence of any of the following: Current hyper- or hypoparathyroidism (parathyroid hormone outside the normal range) Renal disease: Estimated glomerular filtration rate (eGFR) ULN of the laboratory's reference range) at the time of screening. Serum calcium levels may be retested once in case of an elevated serum calcium level within 1.1 x ULN of the laboratory's reference range. Serum phosphorous 1.5 x upper limit of normal (ULN) Total bilirubin (TBL) > 1.5 x ULN (subjects with Gilbert syndrome are eligible) Prior treatment with: romosozumab or other anti-sclerostin antibody f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Romosozumab serum PK parameters: maximum-observed concentration (Cmax), time to Cmax (tmax), area under the curve (AUC) and terminal half life (t1/2);Main Objective: To evaluate the pharmacokinetics (PK) profile following multiple SC doses of romosozumab in children and adolescents with OI;Secondary Objective: To evaluate the safety, tolerability, and immunogenicity profile following multiple SC doses of romosozumab in children and adolescents with OI To evaluate the pharmacodynamic (PD) profile following multiple SC doses of romosozumab in children and adolescents with OI;Timepoint(s) of evaluation of this end point: Investigational product will be dosed on study days 1, 29 and 57 after completion of all pre-dose procedures. Safety assessments, including blood samples for anti-romosozumab antibodies, PK and PD measurements and time points are defined in the Schedule of Assessments as per the Protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Treatment-emergent adverse events, including events of injection site reactions and changes in cranial nerve function.Vital signs, electrocardiograms, physical examinations, and safety laboratory tests, including serum calcium • Incidence of anti-romosozumab antibodies • Bone turnover markers including serum P1NP and serum CTX measurements. • Lumbar spine BMD, bone mineral content (BMC), bone area, and BMD Z-score as assessed by dual-energy X-ray absorptiometry (DXA);Timepoint(s) of evaluation of this end point: Investigational product will be dosed on study days 1, 29 and 57 after completion of all pre-dose procedures. Safety assessments, including blood samples for anti-romosozumab antibodies, PK and PD measurements and time points are defined in the Schedule of Assessments as per the Protocol. | — |
Countries
France, Germany, Greece, Hungary, Italy, Spain, Turkey
Outcome results
None listed