A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Infigratinib in Children 3 to <18 Years of Age With Achondroplasia: PROPEL 3

QED Therapeutics, a BridgeBio company28 sites in 10 countries114 target enrollmentNovember 10, 2023

ConditionsAchondroplasia

InterventionsInfigratinib 0.25 mg/kg/day Placebo Comparator 0.25 mg/kg/day

DrugsInfigratinib 0.25 mg/kg/day Placebo Comparator 0.25 mg/kg/day

Overview

Phase: Phase 3
Intervention: Infigratinib 0.25 mg/kg/day
Conditions: Achondroplasia
Sponsor: QED Therapeutics, a BridgeBio company
Enrollment: 114
Locations: 28
Primary Endpoint: Change from baseline (BL) in annualized height velocity (cm/year)
Status: Completed
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of infigratinib in children and adolescents with achondroplasia (ACH) who have completed at least 26 weeks of participation in the QED-sponsored study PROPEL (QBGJ398-001).

Registry

clinicaltrials.gov

Start Date

November 10, 2023

End Date

December 18, 2025

Last Updated

last month

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

QED Therapeutics, a BridgeBio company

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject must be 3 to \<18 years of age at screening with growth potential defined as annualized height velocity of \>1.5 cm/year over a period of at least 6 months of participation in the PROPEL observational study (QBGJ398-001), pubertal Tanner stage ≤4, and bone age ≤13 years in females and ≤15 years in males.
•Type of Subject and Disease Characteristics
•Subjects who have a diagnosis of ACH that has been documented clinically and confirmed by genetic testing.
•Subjects must have completed at least 26 weeks in the PROPEL (QBGJ398-001) study before screening.
•Subjects are able to swallow oral medication.
•Subjects and parent(s), legal guardian(s), or caregivers are willing and able to comply with study visits and study procedures.
•Subjects are ambulatory and able to stand without assistance.
•Sex and Contraceptive/Barrier Requirements
•Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
•If sexually active, subjects, whether male or female, must be willing to use a highly effective method of contraception while taking study drug and for 3 months after the last dose of study drug.

Exclusion Criteria

•Medical Conditions
•Subjects who have hypochondroplasia or short stature condition other than ACH.
•Significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib.
•Current evidence of clinically significant corneal or retinal disorder/keratopathy -confirmed by ophthalmic examination.
•Concurrent circumstance, disease or condition that, in the view of the investigator and/or sponsor, would interfere with study participation or safety evaluations and/or would require treatment with a prohibited medication, and/or would place the subject at high risk for poor treatment compliance or for not completing the study.
•History and/or current evidence of extensive ectopic tissue calcification.
•History of malignancy.
•Prior/Concomitant Therapy
•Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH or short stature.
•Regular long-term treatment (≥3 weeks) with supraphysiologic doses of glucocorticoid therapy (ie, \>15 mg/m2/day of hydrocortisone or equivalent) or treatment with glucocorticoids at anti-inflammatory doses (ie, 2.5-10 mg/kg/day of hydrocortisone or equivalent) for over 3 weeks within 6 months of the screening visit (low-dose local preparations including inhaled steroid for asthma, intranasal sprays for allergies, and topical steroids are allowed).

Arms & Interventions

Infigratinib 0.25 mg/kg/day

Infigratinib at 2, 3.5, 5, 7, 10 mg

Intervention: Infigratinib 0.25 mg/kg/day

Placebo 0.25 mg/kg/day

Placebo Comparator at 2, 3.5, 5, 7, 10 mg

Intervention: Placebo Comparator 0.25 mg/kg/day

Outcomes

Primary Outcomes

Change from baseline (BL) in annualized height velocity (cm/year)

Time Frame: Week 52

Secondary Outcomes

Change from BL in height Z-score (in relation to non-ACH tables)(Week 52)
Absolute and change from baseline in arm span (cm) to standing height ratio(Week 52)
Absolute and change from baseline in head circumference (cm) to standing height ratio(Week 52)
Change in psychomotor function assessed by age-appropriate computerized tests (Detection Test), compared to placebo(Week 52)
Annualized height velocity (cm/year)(Week 52)
Absolute and change from baseline in upper leg to lower leg length ratio (cm)(Week 52)
Change from BL in the Physical Functioning dimension of the Pediatric Quality of Life Generic Core Scale Short Form(Week 52)
Change from BL in height Z-score (in relation to ACH tables)(Week 52)
Change from BL in upper to lower body segment ratio(Week 52)
Absolute value and change in body mass index(Week 52)
Incidence of adverse events(Week 52)
Change from BL in attention assessed by age-appropriate computerized tests (Identification Test)(Week 52)
Absolute and change from baseline in upper arm to forearm length ratio (cm)(Week 52)
Change from BL in annualized height velocity (cm/year) in children 5 years old and older, compared to placebo(Week 52)
Change from BL in working memory assessed by age-appropriate computerized tests (One Back Test)(Week 52)
Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)(Week 52)
Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)(Week 52)
Change from BL in collagen X marker concentration (ug/L)(Week 52)
Change from BL in visual learning assessed by age-appropriate computerized tests (One Card Learning Test)(Week 52)
Evaluate the acceptability and palatability of infigratinib using a 5-point hedonic scale(Week 13)