Achondroplasia
Conditions
Keywords
Skeletal dysplasia, Endochondral ossification, Achondroplasia (ACH), Quality of life in achondroplasia, Fibroblast growth factor receptor 3, FGFR3, Endochondral bone formation, Short-limb disproportionate stature, Bone disease, Functionality in achondroplasia, Musculoskeletal diseases, Osteochondrodysplasia, Genetic diseases, Long - term treatment, Growth, Annualized height velocity, Treatment option, Tyrosine kinase inhibitor
Brief summary
This is a Phase 2, multicenter, open-label, extension (OLE) study to evaluate the long-term safety, tolerability, and efficacy of infigratinib, an FGFR 1-3-selective tyrosine kinase inhibitor, in subjects with ACH who previously completed a QED-sponsored interventional study, and potentially in additional subjects who are naïve to infigratinib treatment. Quality of Life assessments for this subject population will also be evaluated. Treatment-naïve subjects must have at least a 6-month period of growth assessment in study QBGJ398-001 (PROPEL) and will be enrolled in this OLE study only after a dose to be explored further is identified in Phase 2 Study QBGJ398-201 and subjects are not otherwise eligible to enroll in another QED-sponsored Phase 2 or Phase 3 ACH study.
Interventions
DRUGInfigratinib
Infigratinib minitablets or sprinkle capsules to be administered by mouth. In subjects that completed a prior study with infigratinib, the starting dose will be the same as the last dose received in the prior interventional study with infigratinib. Infigratinib dose may be adjusted to 0.25 mg/kg/day (the dose selected to be explored further in the dose escalation portion of Phase 2 study QBGJ398-201 (PROPEL 2)).
Sponsors
QED Therapeutics, a BridgeBio company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Key Rollover Subjects Inclusion Criteria: 1. Pediatric subjects with ACH who have completed a previous QED-sponsored interventional study with infigratinib. 2. Subjects and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures. 3. Subjects are able to swallow oral medication. 4. Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche. 5. If sexually active, subject must be willing to use a highly effective method of contraception while taking study drug and for 1 month after the last dose of study drug. 6. The PI, or a person designated by the PI, will obtain written informed consent from each subject's parent(s), legal guardian(s), or caregiver(s) and the subject's assent, when applicable, before any study-specific activity is performed. Key Rollover Subjects
Exclusion criteria
1. Subject has concurrent circumstance, disease, or condition that, in the view of the PI and/or sponsor, would interfere with study participation or safety evaluations. 2. Subjects who developed a medical condition that will require the initiation of treatment with a prohibited medication. 3. Subjects prematurely discontinued a prior QED-sponsored interventional study with infigratinib 4. Current participation in an ongoing clinical study with a sponsor other than QED 5. Subjects that have reached final height or near final height. Key Inclusion Criteria for Treatment Naïve Subjects 1. Subject must be 3 to \<18 years of age at screening and have growth potential. 2. Subjects and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures. 3. Subjects are able to swallow oral medication. 4. Subjects who have a diagnosis of ACH, documented clinically and confirmed by genetic testing. 5. Subjects have at least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398 001) before study entry. 6. Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche. 7. If sexually active, subject must be willing to use a highly effective method of contraception while taking study drug and for 1 month after the last dose of study drug. 8. The PI, or a person designated by the PI, will obtain written informed consent from each subject's parent(s), legal guardian(s), or caregiver(s) and the subject's assent, when applicable, before any study-specific activity is performed. Key
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment emergent adverse events (TEAE) and serious TEAE | 10 years |
| Changes over time in height Z-score in relation to ACH and non-ACH growth charts | 10 years |
Secondary
| Measure | Time frame |
|---|---|
| Changes in cognitive functions assessed by age-appropriate computerized tests | 10 years |
| Changes over time in absolute height velocity, expressed as height velocity Z-score in relation to ACH and non ACH growth charts | 10 years |
| Changes over time in body proportions | 10 years |
| Changes over time in weight z-score | 10 years |
| Changes overtime in BMI | 10 years |
| Age of puberty onset and time to Tanner stage ≥4 | 10 years |
| Changes over time in number of episodes of otitis media per year | 10 years |
| Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Change (PGI-C) | 10 years |
| Changes over time in range of motion (elbow) | 10 years |
| Changes over time in skeletal abnormalities of the lower extremities and spine | 10 years |
| Changes in health-related Quality of life [HRQoL] as assessed by Pediatric Quality of Life Inventory (PedsQL) | 10 years |
| Changes in health-related Quality of life [HRQoL] as assessed by Quality of Life in Short Stature Youth questionnaire (QoLISSY) | 10 years |
| Overall pain as assessed by Numeric Rating Scale for pain (Pain-NRS) | 10 years |
| Changes in functional abilities as evaluated by Functional Independence Measure for Children (WeeFIM) | 10 years |
| Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Severity (PGI-S) | 10 years |
| Changes over time in number of episodes and/or severity of sleep apnea | 10 years |
| Subject and caregiver evaluation of treatment benefit as assessed by a qualitative interview | 10 years |
Countries
Argentina, Australia, Canada, France, Italy, Norway, Singapore, Spain, United Kingdom, United States
Outcome results
None listed