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Completed

NCT Number: NCT04545554

Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

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).

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Key information

Conditions

Osteogenesis Imperfecta Bone Diseases Bone Diseases, Developmental Collagen Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Genetic Diseases, Inborn Musculoskeletal Diseases Osteochondrodysplasias Skin and Connective Tissue Diseases

Age range

5 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Kepler Universitaetsklinikum GmbH, Linz, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Romosozumab

Drug

Participants will receive multiple doses of romosozumab via a SC injection.

Calcium

Dietary Supplement

All participants will receive daily supplements of elemental calcium.

Vitamin D

Dietary Supplement

All participants will receive daily supplementation with vitamin D.

Primary outcomes

  1. Maximum Observed Serum Concentration (Cmax) of Romosozumab

    Time frame: 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.

  2. Time to Cmax (Tmax) of Romosozumab

    Time frame: 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.

  3. Area Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab

    Time frame: 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.

  4. Accumulation Ratio of Romosozumab

    Time frame: 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.

  5. Terminal Half-life of Romosozumab

    Time frame: 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.

Secondary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Time frame: 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.

  2. Number of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169

    Time frame: 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.

  3. Number of Participants With Anti-romosozumab Antibodies

    Time frame: 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.

  4. Percentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)

    Time frame: 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.

  5. Percentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)

    Time frame: 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.

  6. Percentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine

    Time frame: 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.

  7. Percentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine

    Time frame: 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.

  8. Percentage Change From Baseline in Lumbar Spine Bone Area

    Time frame: 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.

  9. Mean Change From Baseline in Lumbar Spine BMD Z-Score

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Sep 11, 2020
Registry last updated
Apr 15, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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