Clinical trial NCT05408715: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: SEDC
Hypochondrogenesis
Semd, Strudwick Type
Kniest Dysplasia
Keywords: Skeletal Dysplasia
Short Stature
Bone Disease
Lead sponsor: Innoskel
Sponsor class: INDUSTRY
First posted: 2022-06-07
Enrollment: 60
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Infants and children with a type II collagen disorder with short stature from birth to 12 years of age.

Brief summary: 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.


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.

Primary outcomes:
measure: Collection of relevant medical data (retrospective and prospective)
timeFrame: Up to 3 years
measure: Anthropometric measurements
timeFrame: Up to 3 years
measure: Change over time in motor function in children 2 years old and younger
timeFrame: Up to 2 years
measure: Change over time in motor function in children >2 years old
timeFrame: Up to 3 years
measure: Change over time in pulmonary function
timeFrame: Up to 3 years
measure: Change over time in ophthalmological assessment
timeFrame: Up to 3 years
measure: Change over time in skeletal abnormalities
timeFrame: Up to 3 years
measure: Measurement of biomarkers for bone growth
timeFrame: Up to 3 years
measure: Measurement of CNP/ProCNP
timeFrame: Up to 3 years
measure: Measurement of bone-specific alkaline phosphatase (BALP)
timeFrame: Up to 3 years
measure: Change in scores for the pediatric quality of life inventory parent report (PedsQL)
timeFrame: Up to 3 years
measure: Change in PROMIS pediatric short form pain behaviors score
timeFrame: Up to 3 years
measure: Change in fatigue
timeFrame: Up to 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Necker-Enfants Malades
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Centre hospitalier universitaire vaudois, Lausanne
name: Andrea Superti-Furga
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.