Extension Study of Infigratinib in Children With Achondroplasia (ACH)

Phase 2, Open-Label, Long-Term, Extension (OLE) Study of Infigratinib, an FGFR 1-3-Selective Tyrosine Kinase Inhibitor, in Children With Achondroplasia: PROPEL OLE

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.

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 Exclusion Criteria for Treatment Naïve Subjects

1. Subjects who have hypochondroplasia or short stature condition other than ACH (e.g., trisomy 21, pseudoachondroplasia, psychosocial short stature).
2. Subjects who have significant concurrent disease or condition that, in the view of the PI and/or sponsor, would represent an increased risk to the subject or would interfere with study participation or safety evaluations.
3. Subjects who have a history of malignancy.
4. Subjects who are currently receiving treatment with agents that are known strong inducers or inhibitors of cytochrome P450 (CYP) 3A4.
5. Subjects who discontinued treatment with prohibited medications for at least 5 half-lives before screening are eligible.
6. Subjects who have received treatment with growth hormone, insulin-like growth factor 1 (IGF 1), anabolic steroids or any investigational or approved drug for the treatment of ACH in the previous 6 months.
7. Subjects who have significant abnormality in screening laboratory results.
8. Subjects who have had a fracture within 12 months of screening.