Extension Study of Infigratinib in Children with Achondroplasia (ACH)
- Registration Number
- NCT05145010
- Lead Sponsor
- QED Therapeutics, Inc.
- 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. 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 300
- Pediatric subjects with ACH who have completed a previous QED-sponsored interventional study with infigratinib.
- Subjects and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures.
- Subjects are able to swallow oral medication.
- Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
- 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 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
- 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 prematurely discontinued a prior QED-sponsored interventional study with infigratinib
- Current participation in an ongoing clinical study with a sponsor other than QED
- 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 at screening and have growth potential.
- Subjects and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures.
- Subjects are able to swallow oral medication.
- 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.
- Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
- 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 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
- 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 discontinued treatment with prohibited medications for at least 5 half-lives before screening are eligible.
- 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.
- Subjects who have significant abnormality in screening laboratory results.
- Subjects who have had a fracture within 12 months of screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1: Rollover subjects Infigratinib Children who have completed QED-sponsored interventional study with infigratinib (Phase 2 or Phase 3) Arm 2: Treatment naïve subjects Infigratinib Children naïve to infigratinib
- Primary Outcome Measures
Name Time Method 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
Name Time Method Changes over time in range of motion (elbow) 10 years Changes over time in weight z-score 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 absolute height velocity, expressed as height velocity Z-score in relation to ACH and non ACH growth charts 10 years Changes over time in body proportions 10 years Changes overtime in BMI 10 years Changes over time in number of episodes and/or severity of sleep apnea 10 years Changes in health-related Quality of life [HRQoL] as assessed by Quality of Life in Short Stature Youth questionnaire (QoLISSY) 10 years Subject and caregiver evaluation of treatment benefit as assessed by a qualitative interview 10 years Changes in health-related Quality of life [HRQoL] as assessed by Pediatric Quality of Life Inventory (PedsQL) 10 years Changes in cognitive functions assessed by age-appropriate computerized tests 10 years Changes over time in skeletal abnormalities of the lower extremities and spine 10 years Overall pain as assessed by Numeric Rating Scale for pain (Pain-NRS) 10 years Changes in functional abilities as evaluated by Functional Independence Measure for Children (WeeFIM) 10 years Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Severity (PGI-S) 10 years Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Change (PGI-C) 10 years
Trial Locations
- Locations (19)
University Hospitals Bristol and Weston NHS Foundation Trust
🇬🇧Bristol, United Kingdom
USCF Benioff Children's Hospital, Oakland
🇺🇸Oakland, California, United States
Nemours Alfred I. Dupont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Murdoch Children's Hospital
🇦🇺Parkville, Victoria, Australia
Stollery Children's Hospital
🇨🇦Edmonton, Alberta, Canada
Hopital Femme Mere Enfant
🇫🇷Lyon, France
Hopital Necker-Enfants Malades
🇫🇷Paris, France
Hopital des Enfants
🇫🇷Toulouse, France
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Vithas San José
🇪🇸Vitoria-Gasteiz, Álava, Spain
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 Kingdom