Study of Infigratinib in Children With Achondroplasia

Achondroplasia Clinical Trial

Official title:

Phase 2, Open-Label, Dose-Escalation and Dose-Expansion Study of Infigratinib, an FGFR 1-3-Selective Tyrosine Kinase Inhibitor, in Children With Achondroplasia: PROPEL 2

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04265651
• Other study ID #: QBGJ398-201
• Status: Recruiting
• Phase: Phase 2
• Start date: March 10, 2020
• Est. completion date: December 2024

Study information

• Verified date: February 2023
• Source: QED Therapeutics, Inc.
• Contact: QED Therapeutics VP, Clinical Development
• Phone: 1-877-280-5655
• Email: PROPELstudyinfo[@]QEDTX.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: December 2024
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 11 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent by participant or parent(s) or legally authorized representative (LAR) and signed informed assent by the participant (when applicable).

2. Diagnosis of ACH, documented clinically and confirmed by genetic testing.

3. At least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398-001) before study entry.

4. Ambulatory and able to stand without assistance

5. Able to swallow oral medication.

Exclusion Criteria:

1. Hypochondroplasia or short stature condition other than ACH.

2. In females, having had their menarche.

3. Height < -2 or > +2 standard deviations for age and sex based on reference tables on growth in children with ACH.

4. Significant concurrent disease or condition that, in the view of the Investigator and/or Sponsor, would confound assessment of efficacy or safety of infigratinib.

5. Current evidence of corneal or retinal disorder/keratopathy.

6. History of malignancy.

7. Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration.

8. 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.

9. Treatment with a C-type natriuretic peptide (CNP) analog, fibroblast growth factor (FGF) ligand trap, or treatment targeting FGFR inhibition at any time.

10. Regular long-term treatment (>3 weeks) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable).

11. Treatment with any other investigational product or investigational medical device for the treatment of ACH or short stature.

12. Previous limb-lengthening surgery or guided growth surgery.

13. Fracture within 12 months of screening.

Related Conditions & MeSH terms

• Achondroplasia

Intervention

Drug:
• Infigratinib 0.016 mg/kg
Initial cohort dose of infigratinib at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
• Infigratinib 0.032 mg/kg
Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
• Infigratinib 0.064 mg/kg
Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
• Infigratinib 0.128 mg/kg
Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
• Infigratinib 0.25 mg/kg
Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.

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	Vithas Hospital San José	Vitoria-Gasteiz	Álava
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	University Hospitals Bristol and Weston NHS Foundation Trust	Bristol
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Evelina London Children's Hospital	London
United Kingdom	Manchester University Children's Hospital	Manchester
United Kingdom	Sheffield Children's Hospital	Sheffield	England
United States	Johns Hopkins School of Medicine	Baltimore	Maryland
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	UCSF Benioff Children's Hospital	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 (TEAEs) that lead to dose decrease or discontinuation		Up to 18 months
Primary	Change from baseline in annualized height velocity		Up to 18 months
Primary	PK parameters of infigratinib (Cmax- PK substudy only)		21 days
Primary	PK parameters of infigratinib (Clast- PK substudy only)		21 days
Primary	PK parameters of infigratinib (Tmax- PK substudy only)		21 days
Primary	PK parameters of infigratinib (AUC24- PK substudy only)		21 days
Primary	PK parameters of infigratinib (T1/2- PK substudy only)		21 days
Primary	PK parameters of infigratinib (AUCinf- PK substudy only)		21 days
Primary	PK parameters of infigratinib (CL/F- PK substudy only)		21 days
Primary	PK parameters of infigratinib (Vz/F- PK substudy only)		21 days
Primary	PK parameters of infigratinib (Racc- PK substudy only)		21 days
Secondary	Incidence of adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability		Up to 18 months
Secondary	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
Secondary	Absolute and change from baseline in weight (kg)		Up to 18 months
Secondary	Absolute and change from baseline in sitting height (cm)		Up to 18 months
Secondary	Absolute and change from baseline in head circumference (cm)		Up to 18 months
Secondary	Absolute and change from baseline in upper and lower arm length (cm)		Up to 18 months
Secondary	Absolute and change from baseline in thigh length (cm)		Up to 18 months
Secondary	Absolute and change from baseline in knee height (cm)		Up to 18 months
Secondary	Absolute and change from baseline in arm span (cm)		Up to 18 months
Secondary	Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)		Up to 18 months
Secondary	Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)		Up to 18 months
Secondary	Changes in pharmacodynamic parameters by assessing collagen X marker		Up to 18 months
Secondary	Changes in pharmacodynamic parameters by assessing serum type 1 collagen c-telopeptide		Up to 18 months
Secondary	Changes in pharmacodynamic parameters by assessing procollagen type 1 N-telopeptide		Up to 18 months
Secondary	Changes in pharmacodynamic parameters by assessing bone-specific alkaline phosphatase		Up to 18 months