Infigratinib for Achondroplasia

Recruiting at 22 trial locations

Overseen By QED Therapeutics VP, Clinical Development

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: QED Therapeutics, Inc.

Must not be taking: CYP3A4 modulators, Phosphorus/Calcium increasers

Disqualifiers: Hypochondroplasia, Menarche, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a medicine called infigratinib in children aged 3 to 11 years with Achondroplasia. The medicine works by blocking proteins that cause abnormal bone growth. The children have already participated in an earlier study.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as those that affect CYP3A4 enzymes or increase phosphorus and calcium levels. You also cannot have taken growth hormone, IGF-1, anabolic steroids, or certain other treatments for ACH in the past 6 months.

How does the drug Infigratinib work differently for achondroplasia?

Infigratinib is unique because it directly targets the overactive FGFR3 gene, which is responsible for achondroplasia, by inhibiting its activity. Unlike other treatments that mainly address symptoms, Infigratinib aims to counteract the root cause of the condition. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Infigratinib for treating achondroplasia?

Research shows that Infigratinib, a drug that targets specific growth factor receptors, has improved bone growth in animal models of achondroplasia, suggesting it may help counteract the effects of the condition in humans. ^{1 2 3 6 7}

Who Is on the Research Team?

QED Therapeutics VP, Clinical Development

Principal Investigator

QED Therapeutics

Are You a Good Fit for This Trial?

This trial is for children aged 3-11 with Achondroplasia who were part of the PROPEL study. They must be able to swallow pills, stand unassisted, and not have started puberty. Kids can't join if they've had certain treatments like growth hormones recently or have eye disorders, a history of cancer, or been on long-term steroids.

Inclusion Criteria

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

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

I can walk and stand up on my own without help.

Exclusion Criteria

You have another serious health condition that could make it difficult to evaluate the effectiveness or safety of infigratinib.

I have had a bone break in the last year.

I have a condition causing short stature, but it's not achondroplasia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive infigratinib with doses adjusted based on weight changes approximately every 3 months

6 months

Dose Expansion

An expansion cohort of 20 subjects may begin enrollment to further determine safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of the selected dose

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Infigratinib

Trial Overview The trial tests different doses of Infigratinib (a drug that targets specific growth receptors) in kids with Achondroplasia to see which dose is safe and works best. It's an open-label study where everyone knows what treatment they're getting, involving both increasing the dose over time and expanding it to more patients.

How Is the Trial Designed?

Group I: Infigratinib 0.25 mg/kg Experimental Treatment 1 Intervention

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.

Group II: Infigratinib 0.128 mg/kg Experimental Treatment 1 Intervention

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.

Group III: Infigratinib 0.064 mg/kg Experimental Treatment 1 Intervention

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.

Group IV: Infigratinib 0.032 mg/kg Experimental Treatment 1 Intervention

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.

Group V: Infigratinib 0.016 mg/kg Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

QED Therapeutics, Inc.

Lead Sponsor

Trials

11

Recruited

1,200+

Published Research Related to This Trial

The pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 effectively reduces FGFR3 hyperactivity, leading to improvements in bone growth and structure in a mouse model of achondroplasia after just 10 days of treatment.

NVP-BGJ398 not only corrects abnormalities in the growth plate and skeleton but also inhibits key signaling pathways associated with FGFR3, suggesting it could be a promising therapeutic option for treating achondroplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. Komla-Ebri, D., Dambroise, E., Kramer, I., et al.[2020]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Infigratinib, a selective FGFR1-3 tyrosine kinase inhibitor, alters dentoalveolar development at high doses. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Medical complications in children with achondroplasia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

A height-for-age growth reference for children with achondroplasia: Expanded applications and comparison with original reference data. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

In vitro and in vivo characterization of Recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia. [2021]