Infigratinib for Achondroplasia

(PROPEL3 Trial)

Not currently recruiting at 31 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: QED Therapeutics, Inc., a Bridgebio company

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a drug called infigratinib for children and teens with achondroplasia, a type of dwarfism. The study compares the drug to a placebo (a non-active substance) to evaluate its effectiveness in promoting growth. Children and teens diagnosed with achondroplasia through genetic testing and who have participated in a previous related study for at least six months might be suitable candidates. Participants should be able to take oral medication and attend study visits. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that infigratinib is generally safe for children with achondroplasia. In past studies, most children experienced only mild side effects. Specifically, one study found that 54% of side effects were mild. Severe reactions rarely led to dose adjustments or treatment discontinuation. Another study demonstrated that infigratinib was safe for up to 18 months, with ongoing positive results. Overall, evidence suggests that infigratinib is safe for children with achondroplasia, with most side effects being manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for achondroplasia?

Researchers are excited about Infigratinib for achondroplasia because it offers a new approach compared to the current standard treatments, which often focus on managing complications rather than addressing the root cause. Unlike other treatments, Infigratinib is a small molecule that targets the fibroblast growth factor receptor 3 (FGFR3), which plays a key role in bone growth regulation. By directly inhibiting this receptor, Infigratinib has the potential to promote bone growth more effectively and safely, providing a promising alternative for individuals with achondroplasia.

What evidence suggests that infigratinib might be an effective treatment for achondroplasia?

Research has shown that infigratinib, which participants in this trial may receive, may help treat achondroplasia, a condition affecting bone growth. Studies have found that children taking infigratinib grew taller at a faster rate over 18 months. This suggests that infigratinib could help children with achondroplasia grow more quickly. Most children tolerated the treatment well, experiencing no serious side effects. These findings suggest that infigratinib could be effective in managing achondroplasia. ^{1 2 3 4 5}

Who Is on the Research Team?

QED Therapeutics, Inc. Medical Director, Clinical Development

Principal Investigator

QED Therapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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., a Bridgebio company

Lead Sponsor

QED Therapeutics, a BridgeBio company

Lead Sponsor

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39555818/

Oral Infigratinib Therapy in Children with Achondroplasia The primary safety outcome was the incidence of adverse events that led to a decrease in the dose or discontinuation of infigratinib. The ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMc2504219

Oral Infigratinib Therapy in Children with Achondroplasia In the trial by Savarirayan et al., the investigators report that the majority of children had adverse events that were either mild (in 54%) or ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2949774425001281

Oral infigratinib for children with achondroplasia: Month 18 ... Oral infigratinib was well-tolerated for up to 18 months. Daily doses of 0.25 mg/kg infigratinib resulted in significant and sustained increases in AHV as well ...

4. bridgebio.com bridgebio.com/news/bridgebio-pharma-announces-publication-in-the-new-england-journal-of-medicine-of-phase-2-propel-2-study-of-infigratinib-for-children-living-with-achondroplasia/

BridgeBio Pharma Announces Publication in the New ... Positive 18-month results from PROPEL 2, a Phase 2 trial of the investigational therapy infigratinib in children with achondroplasia, were published as an ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06164951

NCT06164951 | A Study to Evaluate the Efficacy and ... This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of infigratinib in children and ...