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

• Register: EUCTR
• Last refreshed on: 14 October 2024
• Main ID: EUCTR2017-004972-74-IT
• Date of registration: 21/01/2021
• Prospective Registration: No
• Primary sponsor: AMGEN INC.
• Public title: An Open-label, Ascending Multiple dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents with Osteogenesis Imperfecta
• Scientific title: An Open-label, Ascending Multiple-dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Romosozumab in Children and Adolescents With Osteogenesis Imperfecta - NA
• Date of first enrolment: 21/10/2020
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004972-74
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, France, Germany, Greece, Hungary, Italy, Spain, Turkey

Contacts

• Name: Medical Information
• Affiliation: Amgen S.r.l.

• Name: Medical Information
• Affiliation: Amgen S.r.l.

Key inclusion & exclusion criteria

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

*Please, refer to protocol for the full list


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Osteogenesis imperfecta (OI) is a group of genetic skeletal disorders characterized by increased bone fragility, low bone mass, and increased bone turnover contributing to osteoporosis, fractures, and other conditions. OI is the most common form of primary osteoporosis in children with an estimated incidence of 1 per 25,000 live births.
MedDRA version: 20.0 Level: PT Classification code 10031243 Term: Osteogenesis imperfecta System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

Intervention(s)

Trade Name: Evenity 105mg
Product Name: Romosozumab
Product Code: [AMG 785]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ROMOSOZUMAB
CAS Number: 909395-70-6
Current Sponsor code: AMG 785
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-

Trade Name: CALCIUM D3 SANDOZ - 1000 MG + 880 U.I. COMPRESSE EFFERVESCENTI 30 COMPRESSE DIVISIBILI
Product Name: Calcium D3
Product Code: [vitamina D e calcio]
Pharmaceutical Form: Effervescent tablet
INN or Proposed INN: CALCIO CARBONATO/COLECALCIFEROLO
Current Sponsor code: vitamina D e calcio
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Primary Outcome(s)

Main Objective: To evaluate the pharmacokinetics (PK) profile following multiple SC doses of romosozumab in children and adolescents with OI

Primary end point(s): Romosozumab serum PK parameters: maximum-observed concentration (Cmax), time to Cmax (tmax), area under the curve (AUC) and terminal half life (t1/2)

Secondary Objective: - To evaluate the safety, tolerability, and immunogenicity profile following multiple SC doses of romosozumab in children and adolescents with OI
- To evaluate the pharmacodynamic (PD) profile following multiple SC doses of romosozumab in children and adolescents with OI

Timepoint(s) of evaluation of this end point: Investigational product will be dosed on study days 1, 29 and 57 after completion of all pre-dose procedures. Safety assessments, including blood samples for anti-romosozumab antibodies, PK and PD measurements and time points are defined in the Schedule of
Assessments as per the Protocol.

Secondary Outcome(s)

Secondary end point(s): • Treatment-emergent adverse events, including events of injection site reactions and changes in cranial nerve function.Vital signs, electrocardiograms, physical examinations, and safety laboratory tests, including serum calcium
• Incidence of anti-romosozumab antibodies
• Bone turnover markers including serum P1NP and serum CTX measurements.
• Lumbar spine BMD, bone mineral content (BMC), bone area, and BMD Z-score as assessed by dual-energy X-ray absorptiometry (DXA)

Timepoint(s) of evaluation of this end point: Investigational product will be dosed on study days 1, 29 and 57 after completion of all pre-dose procedures. Safety assessments, including blood samples for anti-romosozumab antibodies, PK and PD measurements and time points are defined in the Schedule of Assessments as per the Protocol.

Secondary ID(s)

2017-004972-74-HU

20160227

Source(s) of Monetary Support

Amgen Inc.

Ethics review

Status: Approved
Approval date: 21/10/2020
Contact:

Results

• Results available: Yes
• Date Posted: 13/10/2023
• Date Completed: 30/03/2023
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004972-74/results