An Open-label, Ascending Multiple dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents with Osteogenesis Imperfecta

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 16

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

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 < lower limit
normal [LLN]), malabsorption should be 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
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
History of hyper- or hypothyroidism, unless subject is on stable therapy
> 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) < 60
mL/min/1.73 m2 (calculated by the bedside Schwartz equation at
screening)
eGFR (mL/min/1.73 m2)= 0.413 X (height/serum creatinine)
(Height is in centimeters, and serum creatinine is in mg/dL)
Current hypocalcemia (albumin-adjusted serum calcium < LLN of the
laboratory's reference range) or hypercalcemia (albumin-adjusted serum
calcium > 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 < LLN
Vitamin D insufficiency, defined as 25OHD levels < 20 ng/mL; vitamin D repletion will be allowed and subjects may be retested.
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 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
fluoride or strontium for bone disease
parathyroid hormone (PTH)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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