Infigratinib for Achondroplasia

(PROPEL3 Trial)

Recruiting at 30 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: QED Therapeutics, Inc.

Must not be taking: CYP3A4 agents, Antacids

Disqualifiers: Hypochondroplasia, Malignancy, Ectopic calcification, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

110 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take certain medications like strong inducers or inhibitors of CYP3A4, or medications that alter stomach acidity for more than a week. It's best to discuss your current medications with the trial team.

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

Infigratinib is a drug that targets the FGFR3 gene, which is overactive in achondroplasia, and is being studied as a direct treatment to counteract this overactivity. Similar drugs, like NVP-BGJ398, have shown promise in mouse models by improving bone growth and correcting skeletal abnormalities associated with achondroplasia. ^{1 2 3 4 5}

Is Infigratinib safe for humans?

Infigratinib, a type of drug called a tyrosine kinase inhibitor, has been studied for its effects on achondroplasia and other conditions. While it shows promise in treating certain conditions, some studies have reported toxic effects on the liver, lungs, and kidneys in animal models, indicating potential safety concerns that need further investigation in humans. ^{1 3 4 5 6}

How is the drug Infigratinib unique for treating achondroplasia?

Infigratinib is unique because it directly targets the overactive FGFR3 gene, which is responsible for achondroplasia, using a selective tyrosine kinase inhibitor. Unlike other treatments that mainly address symptoms, Infigratinib aims to counteract the root cause of the condition. ^{1 5 6 7 8}

Research Team

QED Therapeutics, Inc. Medical Director, Clinical Development

Principal Investigator

QED Therapeutics

Eligibility Criteria

This trial is for children and adolescents aged 3 to <18 with achondroplasia, who are still growing and have completed at least 26 weeks in the PROPEL study. They must be able to swallow pills, stand without help, not be fully sexually mature, and girls of a certain age or menstruating must test negative for pregnancy.

Inclusion Criteria

If you are sexually active, you must be willing to use a very effective form of birth control while taking the study drug and for 3 months after stopping the study drug.

I am between 3 and 18 years old, growing more than 1.5 cm a year, not fully through puberty, and meet the bone age requirement.

I can stand and walk without help.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive infigratinib or placebo for the duration of the study

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Infigratinib
• Placebo Comparator

Trial Overview The trial tests Infigratinib against a placebo in participants with achondroplasia. It's a Phase 3 study where patients are randomly assigned to receive either the drug or an inactive substance (placebo), but neither they nor the doctors know which one they're getting.

Participant Groups

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

Infigratinib at 2, 3.5, 5, 7, 10 mg

Group II: Placebo 0.25 mg/kg/day Placebo Group 1 Intervention

Placebo Comparator at 2, 3.5, 5, 7, 10 mg

Who Is Running the Clinical Trial?

QED Therapeutics, Inc.

Lead Sponsor

Trials

11

Recruited

1,200+

Findings from Research

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]

References

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

Multikinase activity of fibroblast growth factor receptor (FGFR) inhibitors SU5402, PD173074, AZD1480, AZD4547 and BGJ398 compromises the use of small chemicals targeting FGFR catalytic activity for therapy of short-stature syndromes. [2020]

2. 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]

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

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

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

Shedding New Light: Novel Therapies for Achondroplasia and Growth Disorders. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

A registry of achondroplasia: a 6-year experience from the Czechia and Slovak Republic. [2022]

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

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

8. England pubmed.ncbi.nlm.nih.gov

FGFR3 targeting strategies for achondroplasia. [2022]