Los requisitos de elegibilidad de los participantes incluyen la edad, el sexo, el tipo y el estadio de la enfermedad, y los problemas de salud o tratamientos previos. Las pautas difieren de un estudio a otro e identifican quiénes pueden o no pueden participar. No hay garantía de que cada persona elegible que desee participar en un ensayo se inscribirá. Comunícate con el equipo del estudio para analizar la elegibilidad del estudio y la posible participación.
Inclusion Criteria:
- Participant has provided informed consent/assent prior to initiation of any study
specific activities/procedures.
OR
- Participant's legally authorized representative has provided informed consent when the
participant is legally too young to provide informed consent and the participant has
provided written assent based on local regulations and/or guidelines prior to any
study-specific activities/procedures being initiated.
- Ambulatory male and female children and adolescents, age 5 to <18 years, including
ambulatory with assistance as defined in the pediatric osteogenesis imperfecta (OI)
population.
- Clinical diagnosis of OI, defined as clinical history consistent with type I, III, or
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, III, or IV OI (eg,
blindness, mental retardation, neuropathy, and craniosynostosis).
o If familial, also must be autosomal dominant.
- Meets at least one of the following:
- 3 or more fractures within the previous 2 years, or
- 1 or more nonvertebral fracture(s) within the previous 2 years and at least 1
prevalent vertebral fracture, or
- 2 or more prevalent vertebral fractures.
- Lumbar spine Z-score of ≤-1.0.
Exclusion Criteria:
Disease Related
- History of an electrophoresis pattern inconsistent with type I, III or IV OI.
- History of known mutation in a gene other than collagen type I alpha 1/collagen type I
alpha 2 (COL1A1/COL1A2) causing OI or other metabolic bone disease.
- History of congenital dislocation of the radial head, interosseous membrane
calcification, or exuberant callus formation.
Other Medical Conditions
- 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 (e.g., osteoporosis
pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis,
hypophosphatasia).
- History of Kawasaki disease, rheumatic myocarditis, ischemic cardiomyopathy, inherited
cardiomyopathies, nephrotic syndrome, familial hypercholesterolemia, stroke, or any
thromboembolic disorder.
- Evidence of untreated or unhealed oral infections.
- Unhealed or planned invasive dental or tooth procedure as determined by treating
dentist; 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.
- History of clinically significant valvular heart disease previously documented with
local echocardiogram results.
- Evidence of any of the following:
- Current hyper- or hypoparathyroidism (parathyroid hormone outside the normal
range).
- Renal disease: Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2
(calculated by the bedside Schwartz equation at screening) eGFR (mL/min/1.73 m^2)
= 0.413 X (height/serum creatinine)
1. (Height is in centimeters, and serum creatinine is in mg/dL).
- Current hypocalcemia (albumin-adjusted serum calcium
[LLN]) or hypercalcemia (albumin-adjusted serum calcium > upper limit of normal
[ULN] of the laboratory's reference range).
- Serum vitamin D <20 ng/mL; rescreening for Vitamin D level < 20 ng/mL will be
allowed, after adequate supplementation.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 1.5 x ULN.
- Total bilirubin (TBL) >1.5 x ULN (participants with Gilbert syndrome are
eligible).
- Serum phosphorus < LLN for age.
- Symptoms associated with skull abnormalities such as basilar invagination, basilar
impression or Chiari malformation (e.g., headache induced by coughing or straining for
stool, visual disturbances, paresthesias or weakness).
- History of malabsorption (in children with serum albumin
clinically ruled out by the investigator to confirm eligibility).
- History of long QT syndrome.
- History of malignancy.
- History of any solid organ or bone marrow transplant.
- History of hyper- or hypothyroidism, unless participant is on stable therapy >
6-months and has supporting laboratory documentation within 6-months prior to or at
screening indicating normal serum thyroid-stimulating hormone (TSH) value.
- Known intolerance to calcium or vitamin D supplements.
Prior/Concomitant Therapy
- Prior treatment with:
- Romosozumab or other anti-sclerostin antibody within 12-months prior to screening.
- Fluoride or strontium for bone disease.
- Parathyroid hormone (PTH) or PTH derivatives within 12-months prior to screening.
- Denosumab within 12-months after the last injection prior to first dose of
romosozumab.
- Administration of any of the following treatments within 3-months prior to screening:
- Systemic glucocorticoids (≥ 5.0 mg prednisone equivalent/day for more than 10 days)
within 3-months prior to screening. Topical and inhaled glucocorticoids will be
allowed.
- Growth hormone (participants on stable dose of growth hormone for at least 3-months
prior to screening will be allowed).
- Calcitonin.
- Other bone active drugs including anticonvulsants (except gabapentin and
benzodiazepines) and heparin (unless low molecular weight heparin).
- Chronic systemic ketoconazole, androgens (except participants who have received
testosterone therapy for physiologic replacement in the setting of documented hormonal
deficiency), adrenocorticotropic hormone (ACTH), cinacalcet, aluminum, lithium,
protease inhibitors, gonadotropin-releasing hormone agonists.
Prior/Concurrent Clinical Study Experience
- Currently receiving treatment in another investigational device or drug study, or less
than 2 years since ending treatment on another investigational device or drug study(ies).
Other investigational procedures while participating in this study are excluded.
Other Exclusions
- Positive blood screen for hepatitis B surface antigen (HbsAg), hepatitis B core
antibody (HBcAb), or hepatitis C antibody (HepCAb), human immunodeficiency virus (HIV)
-1 or -2 antibody. HIV testing to be performed if required by local health
authorities, ethics boards, or based on investigator's judgement.
- Less than 2 evaluable vertebrae by dual-energy x-ray absorptiometry evaluation in the
region of interest, L1-L4, as confirmed by the central imaging laboratory.
- Any planned major surgery, including skeletal surgery (eg, rodding surgery, spinal
surgery) within the next 12-months from Day 1 that would interfere with study
procedures or would require missing of any investigational product
- Female participants of childbearing potential unwilling to use protocol specified
method of contraception during treatment and for an additional 3-months after the last
dose of investigational product or non-investigational product.
- Female participants who are breastfeeding or who plan to breastfeed while on study
through 3-months after the last dose of investigational product or non-investigational
product.
- Female participants planning to become pregnant or donate eggs while on study through
3-months after the last dose of investigational product or non-investigational
product.
- Female participants of childbearing potential with a positive pregnancy test assessed
at Screening and/or Day 1 by a highly sensitive urine or serum pregnancy test.
- Male participants with a female partner of childbearing potential who are unwilling to
practice sexual abstinence (refrain from heterosexual intercourse) or use
contraception during treatment and for an additional 3-months after the last dose of
investigational product or non-investigational product.
- Male participants unwilling to abstain from donating sperm during treatment and for an
additional 3-months after the last dose of investigational product or
non-investigational product.
- Participant has known sensitivity to any of the products to be administered during
dosing.
- Participant likely to not be available to complete all protocol-required study visits
or procedures, and/or to comply with all required study procedures (eg, Clinical
Outcome Assessments) to the best of the participant and investigator's knowledge.
- 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 participant safety or interfere
with the study evaluation, procedures or completion.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 9/12/23. Questions regarding updates should be directed to the study team contact.