Extension Study of Infigratinib in Children With Achondroplasia (ACH)

Achondroplasia Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05145010
• Other study ID #: QBGJ398-203
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: December 6, 2021
• Est. completion date: February 1, 2032

Study information

• Verified date: May 2024
• Source: QED Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. 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 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 280
• Est. completion date: February 1, 2032
• Est. primary completion date: December 1, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

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. 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 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.

6. Subjects who have significant abnormality in screening laboratory results.

7. Subjects who have had a fracture within 12 months of screening.

Related Conditions & MeSH terms

• Achondroplasia

Intervention

Drug:
• Infigratinib
Infigratinib minitablets or sprinkle capsules 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. Infigratinib dose may be adjusted to the dose identified from the dose escalation portion of the Phase 2 study (PROPEL 2).
• Infigratinib
Infigratinib sprinkle capsules to be administered by mouth. Starting dose for the subjects naive to infigratinib will be the one identified during QBGJ398-201 (PROPEL 2).

Locations

Country	Name	City	State
Australia	Murdoch Children's Hospital	Parkville	Victoria
Canada	Stollery Children's Hospital	Edmonton	Alberta
France	Hopital Femme Mere Enfant	Lyon
France	Hopital Necker-Enfants Malades	Paris
France	Hopital des Enfants	Toulouse
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Vithas San José	Vitoria-Gasteiz	Álava
United Kingdom	Birmingham Women's and Children's NHS Foundation Trust	Birmingham
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	St. Thomas' Hospital	London
United Kingdom	Manchester University Children's Hospital	Manchester
United Kingdom	Sheffield Children's Hospital	Sheffield
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	USCF Benioff Children's Hospital, Oakland	Oakland	California
United States	Nemours Alfred I. Dupont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
QED Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events (TEAE) and serious TEAE		10 years
Primary	Changes over time in height Z-score in relation to ACH and non-ACH growth charts		10 years
Secondary	Changes over time in absolute height velocity, expressed as height velocity Z-score in relation to ACH and non ACH growth charts		10 years
Secondary	Changes over time in body proportions		10 years
Secondary	Changes over time in weight z-score		10 years
Secondary	Changes overtime in BMI		10 years
Secondary	Age of puberty onset and time to Tanner stage =4		10 years
Secondary	Changes over time in number of episodes of otitis media per year		10 years
Secondary	Changes over time in number of episodes and/or severity of sleep apnea		10 years
Secondary	Changes over time in range of motion (elbow)		10 years
Secondary	Changes over time in skeletal abnormalities of the lower extremities and spine		10 years
Secondary	Changes in health-related Quality of life [HRQoL] as assessed by Pediatric Quality of Life Inventory (PedsQL)		10 years
Secondary	Changes in health-related Quality of life [HRQoL] as assessed by Quality of Life in Short Stature Youth questionnaire (QoLISSY)		10 years
Secondary	Overall pain as assessed by Numeric Rating Scale for pain (Pain-NRS)		10 years
Secondary	Changes in functional abilities as evaluated by Functional Independence Measure for Children (WeeFIM)		10 years
Secondary	Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Severity (PGI-S)		10 years
Secondary	Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Change (PGI-C)		10 years
Secondary	Subject and caregiver evaluation of treatment benefit as assessed by a qualitative interview		10 years
Secondary	Changes in cognitive functions assessed by age-appropriate computerized tests		10 years