Extension Study of Infigratinib in Children With Achondroplasia (ACH)

Sponsor

QED Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05145010

Collaborator

(none)

280

Enrollment

Locations

Arms

121.9

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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. Treatment-naïve subjects must have at least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398 001) and will be enrolled in this OLE study only after a dose to be explored further is identified in Phase 2 Study QBGJ398-201.

Condition or Disease	Intervention/Treatment	Phase
Achondroplasia	Drug: Infigratinib Drug: Infigratinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

280 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 6, 2021

Anticipated Primary Completion Date :

Dec 1, 2031

Anticipated Study Completion Date :

Feb 1, 2032

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Rollover subjects Children who have completed under QED-sponsored interventional study with infigratinib	Drug: Infigratinib Infigratinib tablets 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.
Experimental: Arm 2: Treatment naïve subjects Children naïve to infigratinib	Drug: Infigratinib Infigratinib tablets to be administered by mouth. Subjects naive to infigratinib may be enrolled at a dose identified during QBGJ398-201 (PROPEL 2).

Arm

Intervention/Treatment

Experimental: Arm 1: Rollover subjects

Children who have completed under QED-sponsored interventional study with infigratinib

Drug: Infigratinib

Infigratinib tablets 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.

Experimental: Arm 2: Treatment naïve subjects

Children naïve to infigratinib

Drug: Infigratinib

Infigratinib tablets to be administered by mouth. Subjects naive to infigratinib may be enrolled at a dose identified during QBGJ398-201 (PROPEL 2).

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Changes over time in absolute height velocity, expressed as height velocity z-score in relation to ACH and non ACH growth chart [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]
Changes over time in number of episodes and/or severity of sleep apnea [10 years]
Changes over time in range of motion (hip, knee and elbow) [10 years]
Changes over time in skeletal abnormalities of the lower extremities and spine [10 years]
Quality of life [QoL] as assessed by Pediatric Quality of Life Inventory (PedsQL) [10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Rollover Subjects Inclusion Criteria:

Pediatric subjects with ACH who have completed study activities in a previous QED-sponsored interventional study with infigratinib.
Subjects and parent(s) or legally authorized representatives (LARs) are willing and able to comply with study visits and study procedures.
Subjects are able to swallow oral medication.
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.
The PI, or a person designated by the PI, will obtain written informed consent from each subject's LAR and the subject's assent, when applicable, before any study-specific activity is performed.

Rollover Subjects Exclusion Criteria:

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.
Subjects who developed a medical condition that will require the initiation of treatment with a prohibited medication.
Subjects that have reached final height or near final height.

Key Inclusion Criteria for Treatment Naïve Subjects

Subject must be 3 to <18 years of age (inclusive) at screening and have growth potential.
Subjects who have a diagnosis of ACH, documented clinically and confirmed by genetic testing.
Subjects have at least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398 001) before study entry.
In girls ≥10 years of age or girls of any age who have experienced menarche, having a negative pregnancy test.
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.
The PI, or a person designated by the PI, will obtain written informed consent from each subject's LAR and the subject's assent, when applicable, before any study-specific activity is performed.

Exclusion Criteria for Treatment Naïve Subjects

Subjects who have hypochondroplasia or short stature condition other than ACH (e.g., trisomy 21, pseudoachondroplasia, psychosocial short stature).
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.
Subjects who have a history of malignancy.
Subjects who are currently receiving treatment with agents that are known strong inducers or inhibitors of cytochrome P450 (CYP) 3A4.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Murdoch Children's Hospital	Parkville	Victoria	Australia	3052
2	Hospital Vithas San José	Vitoria-Gasteiz	Álava	Spain	01012
3	Queen Elizabeth University Hospital	Glasgow		United Kingdom	G12 0XH
4	Sheffield Children's Hospital	Sheffield		United Kingdom	S10 2th