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

NCT05408715 | Recruiting

• 1 other identifier: COL221-101
• Study Type: observational
• Target: 60
• Locations: 2 countries
• Sites: 2

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.

Conditions

SEDC; Hypochondrogenesis; Semd, Strudwick Type; Kniest Dysplasia

Keywords

Skeletal Dysplasia; Short Stature; Bone Disease

Outcome Measures

Primary Outcomes (13)

• Collection of relevant medical data (retrospective and prospective)

  Collection of demographic data, collagen type II-related medical complications, past medical and surgical history and current medication.

  Up to 3 years

• Anthropometric measurements

  Collection of consistent growth measurements (in centimeters).

  Up to 3 years

• Change over time in motor function in children 2 years old and younger

  Motor development will be assessed using the World Health Organisation (WHO) Motor Milestones.

  Up to 2 years

• Change over time in motor function in children >2 years old

  Timed 100-meter walk/run test (T100T). In the T100T, the participant is instructed to walk as fast as possible for a distance of 100 meters. Timed 10-meter walk/run test (T10T). Participants walk 10-meters at self-selected pace. Functional Mobility Scale (FMS) rates the walking ability in three different walking distances.

  Up to 3 years

• Change over time in pulmonary function

  Lung function measured through spirometry in all participants \>4 years of age

  Up to 3 years

• Change over time in ophthalmological assessment

  Standard ophthalmological assessment.

  Up to 3 years

• Change over time in skeletal abnormalities

  Investigators should collect radiographs according standard of care to determine change in skeletal abnormalities and bone growth.

  Up to 3 years

• Measurement of biomarkers for bone growth

  Changes from baseline in serum collagen X fragments.

  Up to 3 years

• Measurement of CNP/ProCNP

  Changes from baseline in serum CNP/ProCNP

  Up to 3 years

• Measurement of bone-specific alkaline phosphatase (BALP)

  Changes from baseline in serum BALP

  Up to 3 years

• Change in scores for the pediatric quality of life inventory parent report (PedsQL)

  The PedsQL parent-proxy report has 23 items that investigate physical, emotional, and social QoL as well as school functioning.

  Up to 3 years

• Change in PROMIS pediatric short form pain behaviors score

  The PROMIS pediatric short form pain behaviors, parent-proxy report is an 8-item measure completed by parents that assesses pain behaviors displayed by their child in the past 7 days. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10, where higher scores indicate increased behaviors due to pain.

  Up to 3 years

• Change in fatigue

  The PROMIS pediatric fatigue parent-proxy report is completed by parents to assess their child's ability to carry out daily activities.

  Up to 3 years

Interventions

Natural History Study OTHER

Longitudinal assessment of symptoms and development of complications in type II collagen disorders

Eligibility Criteria

• Age: Up to 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Innoskel: lead

Study Sites (2)

Hopital Necker-Enfants Malades

Paris, 75015, France

RECRUITING

Hospital Universitario La Paz

Madrid, Spain

RECRUITING

Related Publications (4)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood (5-10 ml) will be collected to measure biomarkers related to bone growth.

MeSH Terms

Conditions

Hypochondrogenesis; Strudwick syndrome; Kniest dysplasia; Mucopolysaccharidosis IV; Dwarfism; Bone Diseases

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Diseases, Developmental; Musculoskeletal Diseases; Endocrine System Diseases

Study Officials

• Andrea Superti-Furga

  Centre hospitalier universitaire vaudois, Lausanne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samantha Parker

CONTACT

+33 (0)4 92 95 29 71; samantha.parker@innoskel.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: June 7, 2022
• Study Start: June 29, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 2, 2023

Record last verified: 2023-09

Locations

FR (1); ES (1)