Overview
This is a Phase 2, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, and efficacy of infigratinib, a fibroblast growth factor receptor (FGFR) 1-3-selective tyrosine kinase inhibitor, in children 3 to 11 years of age with Achondroplasia (ACH) who previously participated in the PROPEL study (Protocol QBGJ398-001) for at least 6 months. The study includes dose escalation with extended treatment, and dose expansion. The study also includes a PK Substudy to fully characterize the pharmacokinetics of infigratinib in children with ACH.
Eligibility
Inclusion Criteria:
- Signed informed consent by participant or parent(s) or legally authorized representative (LAR) and signed informed assent by the participant (when applicable).
- Diagnosis of ACH, documented clinically and confirmed by genetic testing.
- At least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398-001) before study entry.
- Ambulatory and able to stand without assistance
- Able to swallow oral medication.
Exclusion Criteria:
- Hypochondroplasia or short stature condition other than ACH.
- 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.
- 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 corneal or retinal disorder/keratopathy.
- History of malignancy.
- Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration.
- Treatment 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.
- Treatment with a C-type natriuretic peptide (CNP) analog, fibroblast growth factor (FGF) ligand trap, or treatment targeting FGFR inhibition at any time.
- Regular long-term treatment (>3 weeks) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable).
- Treatment with any other investigational product or investigational medical device for the treatment of ACH or short stature.
- Previous limb-lengthening surgery or guided growth surgery.
- Fracture within 12 months of screening.