Clinical trial NCT04035811: Prospective Clinical Assessment Study in Children With Achondroplasia (ACH)
Official title: Prospective Clinical Assessment Study in Children With Achondroplasia: The PROPEL Trial
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Achondroplasia
Keywords: Skeletal dysplasia
Endochondral ossification
Achondroplasia (ACH)
Shortened proximal limbs
Fibroblast growth factor receptor 3
FGFR3
Endochondral bone formation
Short-limb disproportionate dwarfism
Quality of life in achondroplasia
Dwarfism
Bone diseases
Musculoskeletal diseases
Osteochondrodysplasia
Genetic diseases
Inborn
Functional abilities
Average growth velocity
Average height velocity
growth
Congenital
Lead sponsor: QED Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-29
Enrollment: 271
Sex: ALL
Minimum age (years): 30
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children with achondroplasia

Brief summary: This is a long-term, multi-center, observational study in children 2.5 to \<17 years with achondroplasia (ACH). The objective is to evaluate growth, ACH-related medical complications, assessments of health-related quality of life, body pain, functional abilities, cognitive functions, and treatments of study participants. No study medication will be administered.


Eligibility criteria: Key Inclusion Criteria:

* Signed informed consent by study participant or parent(s) or legally authorized representative (LAR) and signed informed assent by the study participant (when applicable)
* Aged 2.5 to \<17 years at study entry
* Diagnosis of ACH
* Study participants and parent(s) or LAR(s) are willing and able to comply with study visits and study procedures

Key Exclusion Criteria:

* Have hypochondroplasia or short stature condition other than ACH (e.g. trisomy 21, pseudoachondroplasia, psychosocial short stature)
* In females, having had their menarche
* Height \< -2 or \> +2 standard deviations for age and sex based on reference tables on growth in children with ACH
* Annualized height growth velocity ≤1.5 cm/year over a period ≥6 months prior to screening
* Current evidence of corneal or retinal disorder/keratopathy
* Current evidence of endocrine alterations of calcium/phosphorus homeostasis
* Have a concurrent disease or condition that in the view of the Investigator and/or Sponsor, may impact growth or where the treatment is known to impact growth.
* Significant abnormality in screening laboratory results.
* Have been treated with growth hormone, insulin-like growth factor 1 (IGF 1), or anabolic steroids in the previous 6 months or long-term treatment (\>3 months) at any time
* Have had regular long-term treatment (\>1 month) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable)
* Have had previous guided growth surgery or limb-lengthening surgery within 12 months prior to screening.

Primary outcomes:
measure: Annualized height velocity (cm/year)
timeFrame: Up to 2 years
Secondary outcomes:
Other outcomes:
measure: Change from baseline in height Z score
timeFrame: Up to 2 years
measure: Change from baseline in upper to lower body ratio (cm)
timeFrame: Up to 2 years
measure: Change from baseline in upper arm to forearm ratio (cm)
timeFrame: Up to 2 years
measure: Change from baseline in upper leg to lower leg ratio (cm)
timeFrame: Up to 2 years
measure: Bone biomarkers (blood)
timeFrame: Up to 2 years
measure: ACH-related NT-AEs
timeFrame: Up to 2 years
measure: ACH-related surgical procedures
timeFrame: Up to 2 years
measure: Changes in health-related quality of life as assessed by Pediatric Quality of Life Inventory (PedsQoL)
timeFrame: Up to 2 years
measure: Changes in health-related quality of life as assessed by Quality of Life in Short Stature Youth questionnaire (QoLISSY)
timeFrame: Up to 2 years
measure: Changes in overall body pain as assessed by Numeric Rating Scale for pain (Pain-NRS)
timeFrame: Up to 2 years
measure: Changes in functional abilities as evaluated by Functional Independence Measure for Children (WeeFIM)
timeFrame: Up to 2 years
measure: Change in psychomotor function assessed by age-appropriate computerized tests (Detection Test)
timeFrame: Up to 2 years
measure: Change in attention assessed by age-appropriate computerized tests (Identification Test)
timeFrame: Up to 2 years
measure: Change in visual learning assessed by age-appropriate computerized tests (One Card Learning Test)
timeFrame: Up to 2 years
measure: Change in working memory assessed by age-appropriate computerized tests (One Back Test)
timeFrame: Up to 2 years
Locations:
city: Oakland
country: United States
facility: Benioff Children's Hospital Oakland
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Nemours Alfred I. Dupont Hospital for Children
state: Delaware
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Madison
country: United States
facility: University of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital de Pediatría SAMIC Prof. Dr. Juan P. Garrahan
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: London
country: Canada
facility: Children's Hospital - London Health Sciences Center
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa
state: Ontario
city: Montréal
country: Canada
facility: University of Montreal
state: Quebec
city: Lyon
country: France
facility: Hopital Femme Mere Enfant
city: Paris
country: France
facility: Hopital Necker-Enfants Malades
city: Toulouse
country: France
facility: Hopital des Enfants
city: Magdeburg
country: Germany
facility: Otto-von-Guericke-University Magdeburg Medical Fakulty
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlino
city: Rome
country: Italy
facility: Rare Disease Unit Fondazione Policlinico A Gemelli IRCCS
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus
city: Oslo
country: Norway
facility: Oslo Universitetssykehus
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Barcelona
country: Spain
facility: Vithas Hospital San Jose
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
state: England
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: London
country: United Kingdom
facility: St. Thomas' Hospital
city: Manchester
country: United Kingdom
facility: Manchester University Children's Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
affiliation: QED Therapeutics
name: QED Therapeutics, Inc. VP, Clinical Development
role: STUDY_DIRECTOR
References:
citation: Savarirayan R, De Bergua JM, Arundel P, McDevitt H, Cormier-Daire V, Saraff V, Skae M, Delgado B, Leiva-Gea A, Santos-Simarro F, Salles JP, Nicolino M, Rossi M, Kannu P, Bober MB, Phillips J 3rd, Saal H, Harmatz P, Burren C, Gotway G, Cho T, Muslimova E, Weng R, Rogoff D, Hoover-Fong J, Irving M. Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies. Ther Adv Musculoskelet Dis. 2022 Mar 21;14:1759720X221084848. doi: 10.1177/1759720X221084848. eCollection 2022.