Achondroplasia in Children MedDRA version: 20.0 Level: LLT Classification code 10000452 Term: Achondroplasia System Organ Class: 100000004850
Conditions
Sponsors
QED Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed informed consent by subject or parent(s) or legally authorized representative (LAR) and signed informed assent by the subject (when applicable). - 3 to 11 years of age (inclusive) at screening. The PK Substudy will only enroll subjects =8 years old. - Diagnosis of ACH, documented clinically and confirmed by genetic testing. - If a girl =10 years of age, negative pregnancy test. -.If sexually active, willing to use a highly effective method of contraception while taking study drug and for 3 months after the last dose of study drug. - Subjects and parent(s) or LAR are willing and able to comply with study visits and study procedures. - Able to swallow oral medication. - Willing to stop consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges, or products containing juice of these fruits while participating in the study; and have not consumed these within 7 days before the first dose of study drug. Are the trial subjects under 18? yes Number of subjects for this age range: 78 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Hypochondroplasia or short stature condition other than ACH (eg, trisomy 21, pseudoachondroplasia, psychosocial short stature). 2. In females, having had their menarche. 3. Height +2 standard deviations for age and sex based on reference tables on growth in children with ACH (Horton 1978). 4. Annualized height velocity =1.5 cm/year over a period =6 months prior to screening. 5. Significant concurrent disease or condition that, in the view of the Investigator and/or Sponsor, would confound assessment of efficacy or safety of infigratinib, including but not limited to cardiac or vascular disease; hyperthyroidism; abnormal thyroid levels or recently diagnosed hypothyroidism that has not been stable on therapy for at least 3 months; insulin-requiring diabetes mellitus; adrenal insufficiency; autoimmune inflammatory disease; inflammatory bowel disease; presence of a functioning ventriculoperitoneal shunt; or diagnosis of severe sleep apnea (pre existing or done at screening based on the sleep study) requiring surgery or continuous positive airway pressure (CPAP) machine. 6. Significant abnormality in screening laboratory results, including but not limited to the following: a. Hemoglobin 1.5× upper limit of normal (ULN). c. AST/SGOT or ALT/SGPT >2× ULN. d. Calculated or measured creatinine clearance of 3 months) at any time. 14. Treatment with a C-type natriuretic peptide (CNP) analog, fibroblast growth factor (FGF) ligand trap, or treatment targeting FGFR inhibition at any time. 15. Regular long-term treatment (=3 weeks) with supraphysiologic doses of glucocorticoid therapy (ie, >15 mg/m2/day of hydrocortisone or equivalence) or treatment with glucocorticoids at anti-inflammatory doses for over 3 weeks within 6 months of the screening visit (low-dose ongoing inhaled steroid for asthma is acceptable). 16. Treatment with any other investigational product or investigatio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Escalation: Primary Objective: To identify a dose of oral infigratinib, based on safety and efficacy evaluations, for children with achondroplasia (ACH) to be used for further study. Dose Expansion: Primary Objective: To provide preliminary evidence of efficacy of oral infigratinib for the treatment of ACH, as assessed by change from baseline in height velocity in children with ACH. PK Substudy: Primary Objective: To evaluate the pharmacokinetic (PK) profile of infigratinib and major active metabolites in children with ACH after administration of oral infigratinib.;Secondary Objective: Dose Escalation, Expansion, and PK Substudy Secondary Objectives • To evaluate the safety and tolerability of oral infigratinib in children with ACH. • To evaluate changes from baseline in anthropometric parameters after administration of oral infigratinib. • To evaluate the pharmacokinetic and pharmacodynamic (PK/PD) profile of infigratinib in children with ACH after administration of oral infigratinib. Exploratory Objective • To evaluate changes in ACH disease burden • To evaluate changes in biomarkers of infigratinib activity;Primary end point(s): Dose Escalation: Primary Endpoint • Treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation. • Change from baseline in height velocity (annualized to cm/year). (Baseline is defined as the annualized height velocity obtained from a minimum of 6 months of observation in the PROPEL study.) Dose Expansion: Primary Endpoint • Change from baseline in height velocity (annualized to cm/year). PK Substudy: Primary Endpoint: • PK parameters of infigratinib and major active metabolites (eg, Cmax, Clast, Tmax, AUC24, T1/2, AUCinf, CL/F, Vz/F, and Racc);Timepoint(s) of evaluation of this end point: The evaluation is scheduled at 6, and 18 months for dose escalation, and 12 months for dose expansion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose Escalation, Dose Expansion, and PK Substudy Secondary Endpoints • Safety evaluations by incidence, type, severity, and causality of adverse events (AEs), serious adverse events (SAEs), laboratory test results (urinalysis, chemistry, hematology), clinically significant changes in vital signs, physical examination (including ophthalmic and dental evaluation), electrocardiograms, and imaging. • Absolute height velocity (annualized to cm/year), expressed numerically and as Z-score in relation to non-ACH tables. • Change from baseline in height velocity (annualized to cm/year) (for PK Substudy only). • Absolute (expressed as absolute value and Z-score in relation to ACH and non-ACH standardized pediatric growth curves) and change from baseline in anthropometric parameters, including body proportions. Anthropometric measurements may include, but may not be limited to, standing height, sitting height, weight, head circumference, upper and lower arm length, thigh length, knee height, and arm span. Body proportion measurement ratios may include, but may not be limited to, upper to lower body segment ratio, upper arm to forearm length ratio, upper leg to lower leg length ratio, arm span to standing height ratio, and head circumference to standing height ratio. • PK parameters (eg, Cmax and Tmax) • Changes in PD parameters (biomarkers of bone turnover that may include type X collagen degradation fragment, collagen X marker [CXM]) (not applicable for the PK Substudy). Exploratory Endpoint • Changes in disease-specific complications, such as changes in mobility (assessed by elbow, hip, and knee range of motion), changes in the number of episodes of otitis media per year, changes in number of episodes and/or severity of sleep apnea, and changes in quality of life [QoL] as assessed by PedsQL (generic core scale short form, child and parent reports). ? Baseline for range of motion and PedsQL will correspond to the values obtained at the basel | — |
Countries
Australia, Canada, France, Spain, United Kingdom, United States
Contacts
Public ContactDaniela Rogoff
QED Therapeutics
Outcome results
None listed