Study of Infigratinib in Children with Achondroplasia
- Conditions
- Achondroplasia
- Interventions
- Registration Number
- NCT04265651
- Lead Sponsor
- QED Therapeutics, Inc.
- Brief Summary
This is a Phase 2, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, and efficacy of infigratinib, a fibroblast growth factor receptor (FGFR) 1-3-selective tyrosine kinase inhibitor, in children 3 to 11 years of age with Achondroplasia (ACH) who previously participated in the PROPEL study (Protocol QBGJ398-001) for at least 6 months. The study includes dose escalation with extended treatment, and dose expansion. The study also includes a PK Substudy to fully characterize the pharmacokinetics of infigratinib in children with ACH.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 84
- Signed informed consent by participant or parent(s) or legally authorized representative (LAR) and signed informed assent by the participant (when applicable).
- Diagnosis of ACH, documented clinically and confirmed by genetic testing.
- At least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398-001) before study entry.
- Ambulatory and able to stand without assistance
- Able to swallow oral medication.
- Hypochondroplasia or short stature condition other than ACH.
- In females, having had their menarche.
- Height < -2 or > +2 standard deviations for age and sex based on reference tables on growth in children with ACH.
- Significant concurrent disease or condition that, in the view of the Investigator and/or Sponsor, would confound assessment of efficacy or safety of infigratinib.
- Current evidence of corneal or retinal disorder/keratopathy.
- History of malignancy.
- Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration.
- Treatment with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids in the previous 6 months or long-term treatment (>3 months) at any time.
- Treatment with a C-type natriuretic peptide (CNP) analog, fibroblast growth factor (FGF) ligand trap, or treatment targeting FGFR inhibition at any time.
- Regular long-term treatment (>3 weeks) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable).
- Treatment with any other investigational product or investigational medical device for the treatment of ACH or short stature.
- Previous limb-lengthening surgery or guided growth surgery.
- Fracture within 12 months of screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Infigratinib 0.016 mg/kg Infigratinib 0.016 mg/kg Dose Escalation: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. Infigratinib 0.032 mg/kg Infigratinib 0.032 mg/kg Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. Infigratinib 0.128 mg/kg Infigratinib 0.128 mg/kg Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. Infigratinib 0.064 mg/kg Infigratinib 0.064 mg/kg Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. Infigratinib 0.25 mg/kg Infigratinib 0.25 mg/kg Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. Dose Expansion: Upon identification of the recommended dose from all cohorts analyzed, an expansion cohort of 20 subjects may begin enrollment to further determine safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of the selected dose.
- Primary Outcome Measures
Name Time Method Change from baseline in annualized height velocity Up to 18 months Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation Up to 18 months PK parameters of infigratinib (Clast- PK substudy only) 21 days PK parameters of infigratinib (Racc- PK substudy only) 21 days PK parameters of infigratinib (Tmax- PK substudy only) 21 days PK parameters of infigratinib (Vz/F- PK substudy only) 21 days PK parameters of infigratinib (Cmax- PK substudy only) 21 days PK parameters of infigratinib (AUCinf- PK substudy only) 21 days PK parameters of infigratinib (AUC24- PK substudy only) 21 days PK parameters of infigratinib (T1/2- PK substudy only) 21 days PK parameters of infigratinib (CL/F- PK substudy only) 21 days
- Secondary Outcome Measures
Name Time Method Incidence of adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability Up to 18 months Absolute height velocity (annualized to cm/year), expressed numerically and as Z-score in relation to ACH and non-ACH tables Up to 18 months Absolute and change from baseline in weight (kg) Up to 18 months Absolute and change from baseline in sitting height (cm) Up to 18 months Absolute and change from baseline in head circumference (cm) Up to 18 months Absolute and change from baseline in upper and lower arm length (cm) Up to 18 months Absolute and change from baseline in thigh length (cm) Up to 18 months Absolute and change from baseline in knee height (cm) Up to 18 months Absolute and change from baseline in arm span (cm) Up to 18 months Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax) Up to 18 months Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax) Up to 18 months Changes in pharmacodynamic parameters by assessing collagen X marker Up to 18 months
Trial Locations
- Locations (19)
Johns Hopkins School of Medicine
🇺🇸Baltimore, Maryland, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
UCSF Benioff Children's Hospital
🇺🇸Oakland, California, United States
Nemours Alfred I. Dupont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Stollery Children's Hospital
🇨🇦Edmonton, Alberta, Canada
Hopital Femme Mere Enfant
🇫🇷Lyon, France
Murdoch Children's Hospital
🇦🇺Parkville, Victoria, Australia
Hopital des Enfants
🇫🇷Toulouse, France
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hopital Necker-Enfants Malades
🇫🇷Paris, France
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Vithas Hospital San José
🇪🇸Vitoria-Gasteiz, Álava, Spain
Sheffield Children's Hospital
🇬🇧Sheffield, England, United Kingdom
Birmingham Children's Hospital
🇬🇧Birmingham, United Kingdom
Manchester University Children's Hospital
🇬🇧Manchester, United Kingdom
Evelina London Children's Hospital
🇬🇧London, United Kingdom
University Hospitals Bristol and Weston NHS Foundation Trust
🇬🇧Bristol, United Kingdom
Queen Elizabeth University Hospital
🇬🇧Glasgow, United Kingdom