Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

Osteogenesis Imperfecta Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04545554
• Other study ID #: 20160227
• Secondary ID: 2017-004972-74
• Status: Completed
• Phase: Phase 1
• Start date: January 21, 2021
• Est. completion date: March 30, 2023

Study information

• Verified date: October 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: March 30, 2023
• Est. primary completion date: March 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

Drug:
• Romosozumab
Participants will receive multiple doses of romosozumab via a SC injection.

Dietary Supplement:
• Calcium
All participants will receive daily supplements of elemental calcium.
• Vitamin D
All participants will receive daily supplementation with vitamin D.

Locations

Country	Name	City	State
Austria	Kepler Universitaetsklinikum GmbH	Linz
Germany	Uniklinik Köln	Koeln
Greece	General Children Hospital Panagioti and Aglaias Kyriakou	Athens
Hungary	Semmelweis Egyetem	Budapest
Italy	IRCCS Ospedale Pediatrico Bambino Gesu	Roma
Spain	Hospital de Cruces	Baracaldo	País Vasco
Spain	Hospital Sant Joan de Deu	Esplugues de Llobregat	Cataluña
Spain	Hospital Universitario de Getafe	Getafe	Madrid
Spain	Hospital Universitari i Politecnic La Fe	Valencia	Comunidad Valenciana
Turkey	Gazi Universitesi Tip Fakultesi	Ankara
Turkey	Koc Universitesi Hastanesi	Istanbul
Turkey	Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)	Izmir
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Austria,  Germany,  Greece,  Hungary,  Italy,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Serum Concentration (Cmax) of Romosozumab	Mean Cmax values following Days 1 and 57 are presented.	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
Primary	Time to Cmax (Tmax) of Romosozumab	Median tmax values following Days 1 and 57 are presented.	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
Primary	Area Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab	Mean AUC(0-28) values following Days 1 and 57 are presented.	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
Primary	Accumulation Ratio of Romosozumab	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.	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
Primary	Terminal Half-life of Romosozumab	Median terminal half-life values at Day 57 are presented.	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	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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.	Day 1 to end of study (up to Day 169); median duration on study was 5.55 months
Secondary	Number of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at 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.	Baseline (Day 1), Day 57, Day 85, and Day 169
Secondary	Number of Participants With Anti-romosozumab Antibodies	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.	Blood samples for anti-romosozumab antibodies were taken Day 1, Day 15, Day 29, Day 85, and Day 169
Secondary	Percentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)	Serum concentrations of the bone turnover marker CTX were determined at pre-specified time points.	Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169
Secondary	Percentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)	Serum concentrations of the bone turnover marker P1NP were determined at pre-specified time points.	Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169
Secondary	Percentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine	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.	DXA scans were during screening (baseline) and at Day 85 and Day 169
Secondary	Percentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine	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.	DXA scans were during screening (baseline) and at Day 85 and Day 169
Secondary	Percentage Change From Baseline in Lumbar Spine Bone Area	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.	DXA scans were during screening (baseline) and at Day 85 and Day 169
Secondary	Mean Change From Baseline in Lumbar Spine BMD Z-Score	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.	DXA scans were during screening (baseline) and at Day 85 and Day 169

External Links

•   AmgenTrials clinical trials website