Clinical trial NCT06164951: A Study to Evaluate the Efficacy and Safety of Infigratinib in Children and Adolescents With Achondroplasia
Official title: A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Infigratinib in Children 3 to <18 Years of Age With Achondroplasia: PROPEL 3
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Achondroplasia
Keywords: Skeletal dysplasia
Endochondral ossification
Quality of life in achondroplasia
Fibroblast growth factor receptor 3
FGFR3
Endochondral bone formation
Short-limb disproportionate dwarfism
Dwarfism
Bone disease
Functionality in achondroplasia
Musculoskeletal diseases
Osteochondrodysplasia
Genetic diseases
Long-term treatment
Growth
Annualized height velocity
Lead sponsor: QED Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-11
Enrollment: 110
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of infigratinib in children and adolescents with achondroplasia (ACH) who have completed at least 26 weeks of participation in the QED-sponsored study PROPEL (QBGJ398-001).


Eligibility criteria: Inclusion Criteria:

1. Subject must be 3 to \<18 years of age at screening with growth potential defined as annualized height velocity of \>1.5 cm/year over a period of at least 6 months of participation in the PROPEL observational study (QBGJ398-001), pubertal Tanner stage ≤4, and bone age ≤13 years in females and ≤15 years in males.

   Type of Subject and Disease Characteristics
2. Subjects who have a diagnosis of ACH that has been documented clinically and confirmed by genetic testing.
3. Subjects must have completed at least 26 weeks in the PROPEL (QBGJ398-001) study before screening.
4. Subjects are able to swallow oral medication.
5. Subjects and parent(s), legal guardian(s), or caregivers are willing and able to comply with study visits and study procedures.
6. Subjects are ambulatory and able to stand without assistance.

   Sex and Contraceptive/Barrier Requirements
7. Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
8. If sexually active, subjects, whether male or female, must be willing to use a highly effective method of contraception while taking study drug and for 3 months after the last dose of study drug.

   Informed Consent
9. Signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol, must be obtained for each subject from their parent(s) or legal guardian and signed informed consent/assent must be obtained from the subject (when applicable)

Exclusion Criteria:

Medical Conditions

1. Subjects who have hypochondroplasia or short stature condition other than ACH.
2. Significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib.
3. Current evidence of clinically significant corneal or retinal disorder/keratopathy -confirmed by ophthalmic examination.
4. Concurrent circumstance, disease or condition that, in the view of the investigator and/or sponsor, would interfere with study participation or safety evaluations and/or would require treatment with a prohibited medication, and/or would place the subject at high risk for poor treatment compliance or for not completing the study.
5. History and/or current evidence of extensive ectopic tissue calcification.
6. History of malignancy.

   Prior/Concomitant Therapy
7. Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH or short stature.
8. Regular long-term treatment (≥3 weeks) with supraphysiologic doses of glucocorticoid therapy (ie, \>15 mg/m2/day of hydrocortisone or equivalent) or treatment with glucocorticoids at anti-inflammatory doses (ie, 2.5-10 mg/kg/day of hydrocortisone or equivalent) for over 3 weeks within 6 months of the screening visit (low-dose local preparations including inhaled steroid for asthma, intranasal sprays for allergies, and topical steroids are allowed).
9. Previous limb-lengthening surgery at any time or planned/expected to have limb-lengthening surgery or guided growth surgery during the study period. Guided growth surgery with plates removed at least 12 months prior to screening is allowed.
10. Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 or prolonged treatment (\>1 week) with medications that alter the pH of the gastrointestinal tract including antacids, H2 antagonists (eg, ranitidine, famotidine), and proton-pump inhibitors (eg, omeprazole).
11. Current evidence of endocrine alterations of calcium/phosphorus homeostasis.

    Diagnostic assessments
12. Subjects who have significant abnormality in screening laboratory results.

    Other Exclusions
13. Having had a fracture of the long bones (ie, extremities) or spine within 12 months prior to screening.
14. Pregnant or breastfeeding at the screening visit or planning to become pregnant (self or partner) at any time during the study.
15. Allergy or hypersensitivity to any components of the study drug.

Primary outcomes:
measure: Change from baseline (BL) in annualized height velocity (cm/year)
timeFrame: Week 52
Secondary outcomes:
measure: Change from BL in height Z-score (in relation to ACH tables)
timeFrame: Week 52
measure: Change from BL in upper to lower body segment ratio
timeFrame: Week 52
measure: Change from BL in height Z-score (in relation to non-ACH tables)
timeFrame: Week 52
measure: Annualized height velocity (cm/year)
timeFrame: Week 52
measure: Absolute and change from baseline in upper arm to forearm length ratio (cm)
timeFrame: Week 52
measure: Absolute and change from baseline in upper leg to lower leg length ratio (cm)
timeFrame: Week 52
measure: Absolute and change from baseline in arm span (cm) to standing height ratio
timeFrame: Week 52
measure: Absolute and change from baseline in head circumference (cm) to standing height ratio
timeFrame: Week 52
measure: Absolute value and change in body mass index
timeFrame: Week 52
measure: Incidence of adverse events
timeFrame: Week 52
measure: Change from BL in annualized height velocity (cm/year) in children 5 years old and older, compared to placebo
timeFrame: Week 52
measure: Change from BL in the Physical Functioning dimension of the Pediatric Quality of Life Generic Core Scale Short Form
timeFrame: Week 52
measure: Change in psychomotor function assessed by age-appropriate computerized tests (Detection Test), compared to placebo
timeFrame: Week 52
measure: Change from BL in attention assessed by age-appropriate computerized tests (Identification Test)
timeFrame: Week 52
measure: Change from BL in visual learning assessed by age-appropriate computerized tests (One Card Learning Test)
timeFrame: Week 52
measure: Change from BL in working memory assessed by age-appropriate computerized tests (One Back Test)
timeFrame: Week 52
measure: Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)
timeFrame: Week 52
measure: Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)
timeFrame: Week 52
measure: Change from BL in collagen X marker concentration (ug/L)
timeFrame: Week 52
measure: Evaluate the acceptability and palatability of infigratinib using a 5-point hedonic scale
timeFrame: Week 13
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: QED Investigative Site
state: California
city: Aurora
country: United States
facility: QED Investigative Site
state: Colorado
city: Baltimore
country: United States
facility: QED Investigative Site
state: Maryland
city: Columbia
country: United States
facility: QED Investigative Site
state: Missouri
city: Cincinnati
country: United States
facility: QED Investigative Site
state: Ohio
city: Nashville
country: United States
facility: QED Investigative Site
state: Tennessee
city: Madison
country: United States
facility: QED Investigative Site
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: QED Investigative Site
state: Capital Federal
city: Parkville
country: Australia
facility: QED Investigative Site
state: Victoria
city: Edmonton
country: Canada
facility: QED Investigative Site
state: Alberta
city: London
country: Canada
facility: QED Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: QED Investigative Site
state: Ontario
city: Montréal
country: Canada
facility: QED Investigative Site
state: Quebec
city: Bron
country: France
facility: QED Investigative Site
city: Paris
country: France
facility: QED Investigative Site
city: Toulouse
country: France
facility: QED Investigative Site
city: Rome
country: Italy
facility: QED Investigative Site
city: Bergen
country: Norway
facility: QED Investigative Site
city: Oslo
country: Norway
facility: QED Investigative Site
city: Singapore
country: Singapore
facility: QED Investigative Site
city: Málaga
country: Spain
facility: QED Investigative Site
city: Vitoria-Gasteiz
country: Spain
facility: QED Investigative Site
city: Birmingham
country: United Kingdom
facility: QED Investigative Site
city: Bristol
country: United Kingdom
facility: QED Investigative Site
city: Glasgow
country: United Kingdom
facility: QED Investigative Site
city: London
country: United Kingdom
facility: QED Investigative Site
city: Manchester
country: United Kingdom
facility: QED Investigative Site
city: Sheffield
country: United Kingdom
facility: QED Investigative Site
Study officials:
affiliation: QED Therapeutics
name: QED Therapeutics, Inc. Medical Director, Clinical Development
role: STUDY_DIRECTOR
References: