A Natural History Study in Children With a Type II Collagen Disorder With Short Stature

Official title

An International Prospective Natural History Study in Children With a Type II Collagen Disorder With Short Stature

Overview

There are relatively few data available on type II collagen disorders, and evidence is lacking on the disease course in relation to symptoms and development of complications, the level of actual disease burden over time as well as data to support identification of possible risk factors. This study aims to build a natural history data set through collection of a number of clinical, imaging, and laboratory assessments that may be specific predictors of type II collagen disorder progression and clinical outcome. Having a type II collagen disorder natural history data set can inform potential efficacy endpoints and biomarkers for future clinical trials. This natural history study will follow up to 60 individuals diagnosed with a type II collagen disorder for up to 3 years. Visits will be conducted every 3 months for the first year and then every 6 months, during which several assessments will be performed in order to learn about the natural course of the disease, including changes in clinical and functional outcomes, imaging and biofluid biomarkers. Some of the study activities include: a physical exam, height measurements, vision and breathing tests and x-ray. A blood sample will be collected once or twice each year. Most of the information collected, the tests done, and the schedule of visits in this study are the same as recommended for regular care of children with a type II collagen disorder.

Interventions

• Other Natural History Study
  Longitudinal assessment of symptoms and development of complications in type II collagen disorders

Primary outcome measures

• Collection of relevant medical data (retrospective and prospective) [Time frame: Up to 3 years]
• Anthropometric measurements [Time frame: Up to 3 years]
• Change over time in motor function in children 2 years old and younger [Time frame: Up to 2 years]
• Change over time in motor function in children >2 years old [Time frame: Up to 3 years]
• Change over time in pulmonary function [Time frame: Up to 3 years]
• Change over time in ophthalmological assessment [Time frame: Up to 3 years]
• Change over time in skeletal abnormalities [Time frame: Up to 3 years]
• Measurement of biomarkers for bone growth [Time frame: Up to 3 years]
• Measurement of CNP/ProCNP [Time frame: Up to 3 years]
• Measurement of bone-specific alkaline phosphatase (BALP) [Time frame: Up to 3 years]

Eligibility criteria

Inclusion criteria

• Confirmed diagnosis of type II collagen disorder with short stature at birth (2 standard deviations (SD) or more below the mean) i.e., Hypochondrogenesis, Kniest, Spondyloepiphyseal dysplasia congenita (SEDc) Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Spondyloperipheral dysplasia (SED).
• Children up to and including 12 years of age, up to the day before their 13th birthday, on the date of consent/assent.
• The patient is sufficiently able, in the opinion of the Investigator, to adhere to the study visit schedule and other protocol requirements.
• The patient's parent(s) or legal guardian(s) has signed written informed consent, according to the local regulations and after all relevant aspects of the study have been explained and discussed.
• The child (depending on local institutional review board/ethical committee requirements) has provided assent.

Exclusion criteria

• Tanner stage 3 or more based on investigator assessment during physical examination
• The patient has a diagnosis of any short stature condition other than a type II collagen disorder.
• The investigator and/or clinical study advisory committee considers the patient has a type II collagen disorder which is not Hypochondrogenesis, SEDc, Kniest, SEMD or SED i.e., Stickler.
• The patient has any other medical condition that may impact growth or where the treatment is known to impact growth, such as but not limited to hypothyroidism or hyperthyroidism, insulin-requiring diabetes mellitus, autoimmune inflammatory disease, autonomic neuropathy or inflammatory bowel disease.
• Treatment in the previous 12 months prior to consent/assent with growth hormones, insulin-like growth factor 1, anabolic steroids, or any other drug expected to affect growth velocity. Brief (up to a few weeks) use of steroids is permitted.
• Participation in any interventional clinical trial or treatment for a type II collagenopathy.
• Has any condition or circumstance that in the view of the investigator places the child at high risk of poor compliance with the visit schedule or of not completing the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 1 center

• Hopital Necker-Enfants Malades — Paris

Spain · 1 center

• Hospital Universitario La Paz — Madrid

Publications

• Savarirayan R, Bompadre V, Bober MB, Cho TJ, Goldberg MJ, Hoover-Fong J, Irving M, Kamps SE, Mackenzie WG, Raggio C, Spencer SS, White KK; Skeletal Dysplasia Management Consortium. Best practice guidelines regarding diagnosis and management of patients with type II collagen disorders. Genet Med. 2019 Sep;21(9):2070-2080. doi: 10.1038/s41436-019-0446-9. Epub 2019 Jan 30. PMID 30696995
• Oh CW, Thacker MM, Mackenzie WG, Riddle EC. Coxa vara: a novel measurement technique in skeletal dysplasias. Clin Orthop Relat Res. 2006 Jun;447:125-31. doi: 10.1097/01.blo.0000203476.81302.24. PMID 16505708
• Dhiman N, Albaghdadi A, Zogg CK, Sharma M, Hoover-Fong JE, Ain MC, Haider AH. Factors associated with health-related quality of life (HRQOL) in adults with short stature skeletal dysplasias. Qual Life Res. 2017 May;26(5):1337-1348. doi: 10.1007/s11136-016-1455-7. Epub 2016 Nov 19. PMID 27866314
• Graham HK, Harvey A, Rodda J, Nattrass GR, Pirpiris M. The Functional Mobility Scale (FMS). J Pediatr Orthop. 2004 Sep-Oct;24(5):514-20. doi: 10.1097/00004694-200409000-00011. PMID 15308901

Identifiers

NCT: NCT05408715 · COL221-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗