Clinical trial NCT04545554: Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
Official title: An Open-label, Ascending Multiple-dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteogenesis Imperfecta
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-09-11
Enrollment: 25
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the pharmacokinetics (PK) profile following multiple subcutaneous (SC) doses of romosozumab in children and adolescents with Osteogenesis Imperfecta (OI).


Eligibility criteria: Inclusion Criteria:

* Ambulatory male or female children 5 to less than 18 years of age 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 and lack of additional features unrelated to type I-IV OI

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 1/collagen type I alpha 2 (COL1AI/COL1A2) causing OI or other metabolic bone disease
* 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, nephrotic syndrome, familial hypercholesterolemia, stroke, or any thromboembolic disorder
* Unhealed fracture as defined by orthopedic opinion
* Symptoms associated with skull abnormalities such as basilar invagination, basilar impression or Chiari malformation
* Prior treatment with anti-sclerostin antibody, fluoride or strontium, parathyroid hormone (PTH) within 12 months prior to screening, denosumab within 12 months or zoledronic acid within 6 months prior to first dose
* Less than 2 evaluable vertebrae by DXA evaluation in the region of interest, L1 - L4, as confirmed by the central imaging laboratory.
* Clinically significant valvular heart disease based on local echocardiogram (ECHO) results.

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Romosozumab
timeFrame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57
measure: Time to Cmax (Tmax) of Romosozumab
timeFrame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57
measure: Area Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab
timeFrame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57
measure: Accumulation Ratio of Romosozumab
timeFrame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57
measure: Terminal Half-life of Romosozumab
timeFrame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Day 57
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 to end of study (up to Day 169); median duration on study was 5.55 months
measure: Number of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169
timeFrame: Baseline (Day 1), Day 57, Day 85, and Day 169
measure: Number of Participants With Anti-romosozumab Antibodies
timeFrame: Blood samples for anti-romosozumab antibodies were taken Day 1, Day 15, Day 29, Day 85, and Day 169
measure: Percentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)
timeFrame: Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169
measure: Percentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)
timeFrame: Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169
measure: Percentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine
timeFrame: DXA scans were during screening (baseline) and at Day 85 and Day 169
measure: Percentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine
timeFrame: DXA scans were during screening (baseline) and at Day 85 and Day 169
measure: Percentage Change From Baseline in Lumbar Spine Bone Area
timeFrame: DXA scans were during screening (baseline) and at Day 85 and Day 169
measure: Mean Change From Baseline in Lumbar Spine BMD Z-Score
timeFrame: DXA scans were during screening (baseline) and at Day 85 and Day 169
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin
state: Wisconsin
city: Linz
country: Austria
facility: Kepler Universitaetsklinikum GmbH
city: Koeln
country: Germany
facility: Uniklinik Köln
city: Athens
country: Greece
facility: General Children Hospital Panagioti and Aglaias Kyriakou
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
state: Comunidad Valenciana
city: Getafe
country: Spain
facility: Hospital Universitario de Getafe
state: Madrid
city: Baracaldo
country: Spain
facility: Hospital de Cruces
state: País Vasco
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Koc Universitesi Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: