Clinical trial NCT05145010: Extension Study of Infigratinib in Children With Achondroplasia (ACH)
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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Achondroplasia
Keywords: Skeletal dysplasia
Endochondral ossification
Achondroplasia (ACH)
Quality of life in achondroplasia
Fibroblast growth factor receptor 3
FGFR3
Endochondral bone formation
Short-limb disproportionate stature
Bone disease
Functionality in achondroplasia
Musculoskeletal diseases
Osteochondrodysplasia
Genetic diseases
Long - term treatment
Growth
Annualized height velocity
Treatment option
Tyrosine kinase inhibitor
Lead sponsor: QED Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-06
Enrollment: 300
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment emergent adverse events (TEAE) and serious TEAE
timeFrame: 10 years
measure: Changes over time in height Z-score in relation to ACH and non-ACH growth charts
timeFrame: 10 years
Secondary outcomes:
measure: Changes over time in absolute height velocity, expressed as height velocity Z-score in relation to ACH and non ACH growth charts
timeFrame: 10 years
measure: Changes over time in body proportions
timeFrame: 10 years
measure: Changes over time in weight z-score
timeFrame: 10 years
measure: Changes overtime in BMI
timeFrame: 10 years
measure: Age of puberty onset and time to Tanner stage ≥4
timeFrame: 10 years
measure: Changes over time in number of episodes of otitis media per year
timeFrame: 10 years
measure: Changes over time in number of episodes and/or severity of sleep apnea
timeFrame: 10 years
measure: Changes over time in range of motion (elbow)
timeFrame: 10 years
measure: Changes over time in skeletal abnormalities of the lower extremities and spine
timeFrame: 10 years
measure: Changes in health-related Quality of life [HRQoL] as assessed by Pediatric Quality of Life Inventory (PedsQL)
timeFrame: 10 years
measure: Changes in health-related Quality of life [HRQoL] as assessed by Quality of Life in Short Stature Youth questionnaire (QoLISSY)
timeFrame: 10 years
measure: Overall pain as assessed by Numeric Rating Scale for pain (Pain-NRS)
timeFrame: 10 years
measure: Changes in functional abilities as evaluated by Functional Independence Measure for Children (WeeFIM)
timeFrame: 10 years
measure: Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Severity (PGI-S)
timeFrame: 10 years
measure: Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Change (PGI-C)
timeFrame: 10 years
measure: Subject and caregiver evaluation of treatment benefit as assessed by a qualitative interview
timeFrame: 10 years
measure: Changes in cognitive functions assessed by age-appropriate computerized tests
timeFrame: 10 years
Other outcomes:
Locations:
city: Oakland
country: United States
facility: USCF Benioff Children's Hospital, Oakland
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Nemours Alfred I. Dupont Hospital for Children
state: Delaware
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Parkville
country: Australia
facility: Murdoch Children's Hospital
state: Victoria
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Lyon
country: France
facility: Hopital Femme Mere Enfant
city: Paris
country: France
facility: Hopital Necker-Enfants Malades
city: Toulouse
country: France
facility: Hopital des Enfants
city: Singapore
country: Singapore
facility: KK Women's and Children's Hosptial
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Vitoria-Gasteiz
country: Spain
facility: Hospital Vithas San José
state: Álava
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Children's NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: London
country: United Kingdom
facility: St. Thomas' Hospital
city: Manchester
country: United Kingdom
facility: Manchester University Children's Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
affiliation: QED Therapeutics
name: QED Therapeutics SVP, Clinical Development
role: STUDY_DIRECTOR
References: