Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
- Conditions
- Osteogenesis Imperfecta
- Interventions
- Registration Number
- NCT04545554
- Lead Sponsor
- Amgen
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Romosozumab: 12 - < 18 Years of Age Calcium Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D. Romosozumab: 5 - < 12 Years of Age Vitamin D Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D. Romosozumab: 5 - < 12 Years of Age Calcium Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D. Romosozumab: 12 - < 18 Years of Age Vitamin D Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D. Romosozumab: 5 - < 12 Years of Age Romosozumab Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D. Romosozumab: 12 - < 18 Years of Age Romosozumab Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.
- Primary Outcome Measures
Name Time Method Time to Cmax (Tmax) of Romosozumab 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 Median tmax values following Days 1 and 57 are presented.
Terminal Half-life of Romosozumab 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 Median terminal half-life values at Day 57 are presented.
Maximum Observed Serum Concentration (Cmax) of Romosozumab 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 Mean Cmax values following Days 1 and 57 are presented.
Area Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab 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 Mean AUC(0-28) values following Days 1 and 57 are presented.
Accumulation Ratio of Romosozumab 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 The accumulation ratio was calculated as AUC(0-28) at Day 57/AUC(0-28) at Day 1. Mean accumulation ratio values based on analysis at Days 1 and 57 are presented, as pre-specified.
- Secondary Outcome Measures
Name Time Method Percentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine DXA scans were during screening (baseline) and at Day 85 and Day 169 BMD was assessed by dual energy X-ray absorptiometry (DXA) scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.
Number of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169 Baseline (Day 1), Day 57, Day 85, and Day 169 Facial nerve (cranial nerve VII) function was assessed clinically by facial symmetry inspection at rest, followed by assessment of the symmetry of specific facial movements: raising eyebrows, closing the eyes, blowing out the cheeks, smiling, pursing and closing the lips. Results of the cranial nerve examination were classed as 0 = Normal; 1 = Abnormal not clinically significant; and 2 = Abnormal clinically significant. An increase from baseline indicates an increase in abnormal clinical findings on the cranial nerve VII examination.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Day 1 to end of study (up to Day 169); median duration on study was 5.55 months TEAEs were adverse events (AEs) that started on or after first dose of investigational product up to the end of study (up to Day 169). Any clinically significant changes in vital signs, electrocardiogram parameters, physical exam findings, and clinical laboratory parameters were reported as TEAEs.
Injection site reactions were events of interest (EOI) for this study.Percentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX) Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169 Serum concentrations of the bone turnover marker CTX were determined at pre-specified time points.
Number of Participants With Anti-romosozumab Antibodies Blood samples for anti-romosozumab antibodies were taken Day 1, Day 15, Day 29, Day 85, and Day 169 Treatment-boosted anti-romosozumab antibody was defined as binding antibody positive at baseline with a \>4 x increase in magnitude post-baseline. Transient results were defined as negative results at the participant's last time point tested within the study period.
Percentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP) Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169 Serum concentrations of the bone turnover marker P1NP were determined at pre-specified time points.
Percentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine DXA scans were during screening (baseline) and at Day 85 and Day 169 BMC was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.
Percentage Change From Baseline in Lumbar Spine Bone Area DXA scans were during screening (baseline) and at Day 85 and Day 169 Bone area was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.
Mean Change From Baseline in Lumbar Spine BMD Z-Score DXA scans were during screening (baseline) and at Day 85 and Day 169 Lumbar spine BMD was assessed by DXA scans. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from baseline indicated an improvement in lumbar spine BMD.
Trial Locations
- Locations (15)
General Children Hospital Panagioti and Aglaias Kyriakou
🇬🇷Athens, Greece
IRCCS Ospedale Pediatrico Bambino Gesu
🇮🇹Roma, Italy
Koc Universitesi Hastanesi
🇹🇷Istanbul, Turkey
Kepler Universitaetsklinikum GmbH
🇦🇹Linz, Austria
Uniklinik Köln
🇩🇪Koeln, Germany
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Hospital Universitario de Getafe
🇪🇸Getafe, Madrid, Spain
Gazi Universitesi Tip Fakultesi
🇹🇷Ankara, Turkey
Hospital de Cruces
🇪🇸Baracaldo, País Vasco, Spain
Hospital Sant Joan de Deu
🇪🇸Esplugues de Llobregat, Cataluña, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Comunidad Valenciana, Spain
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Semmelweis Egyetem
🇭🇺Budapest, Hungary
The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)
🇹🇷Izmir, Turkey