Study of Infigratinib in Children with Achondroplasia

QED Therapeutics

Status and phase: Completed; Phase 2

Conditions: Achondroplasia

Treatments: Drug: Infigratinib 0.016 mg/kg; Drug: Infigratinib 0.064 mg/kg; Drug: Infigratinib 0.032 mg/kg; Drug: Infigratinib 0.128 mg/kg; Drug: Infigratinib 0.25 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04265651

QBGJ398-201

Details and patient eligibility

About

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.

Enrollment: 84 patients

Sex: All

Ages: 3 to 11 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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84 participants in 5 patient groups

Infigratinib 0.016 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Infigratinib 0.016 mg/kg

Infigratinib 0.032 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Infigratinib 0.032 mg/kg

Infigratinib 0.064 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Infigratinib 0.064 mg/kg

Infigratinib 0.128 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Infigratinib 0.128 mg/kg

Infigratinib 0.25 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Infigratinib 0.25 mg/kg