Infigratinib for Achondroplasia

No longer recruiting at 22 trial locations

Overseen By QED Therapeutics VP, Clinical Development

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: QED Therapeutics, Inc., a Bridgebio company

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests infigratinib, a medication designed to help children with achondroplasia (a form of dwarfism), by evaluating its safety, tolerability, and effectiveness. The trial uses different doses to determine the best one for improving growth. It includes children aged 3 to 11 who have participated in a previous study called PROPEL for at least six months. Participants must be able to walk unassisted and take oral medication. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that infigratinib is likely to be safe for children with achondroplasia?

Research has shown that infigratinib, a treatment for achondroplasia (a type of short-limbed dwarfism), is generally safe for children. Studies have found that its side effects are usually mild, such as an upset stomach or changes in appetite. More serious side effects are rare but can include higher levels of phosphate in the blood, which doctors monitor closely during treatment. Clinical trials have demonstrated a positive safety record, indicating that most children can take infigratinib without major problems. Overall, the evidence suggests that infigratinib is safe for children with this condition. ^{1 2 3 4 5}

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

Infigratinib is unique because it targets achondroplasia by inhibiting the fibroblast growth factor receptor 3 (FGFR3), which is different from current treatments like growth hormone therapy that primarily focus on stimulating overall growth. Unlike other treatments, Infigratinib offers a more targeted approach by directly addressing the genetic cause of achondroplasia. This specificity in action offers hope for more effective and potentially quicker results, making researchers excited about its potential to improve outcomes for individuals with this condition.

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

Research has shown that infigratinib, a new drug being tested for achondroplasia, has produced promising results in early studies. One study found that 73% of children taking infigratinib grew more than 25% faster than expected for children with achondroplasia over 18 months, indicating a quicker growth rate. The treatment was generally safe, with no major safety issues reported. These findings suggest that infigratinib might help children with achondroplasia grow taller and is well-tolerated. Participants in this trial will receive different dosages of infigratinib to further evaluate its safety and effectiveness. ^{1 2 6 7 8}

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., 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 Conclusions: The administration of oral infigratinib did not result in any apparent major safety signal and increased the annualized height ...

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

Oral Infigratinib Therapy in Children with Achondroplasia The clinical development of infigratinib in children with achondroplasia includes the evaluation of its safety and efficacy at younger ages, ...

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

Oral infigratinib for children with achondroplasia: Month 18 ... Of 10/11 children with positive AHV changes from baseline at Month 18, 73% experienced a >25% AHV increase. Mean (SD) change from baseline in height z-score was ...

4. 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 ...

5. 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 ...

6. bridgebio.com bridgebio.com/news/5706-2/

Positive Results from a Phase 2 Trial of Infigratinib BridgeBio Pharma announces positive interim results from a Phase 2 trial of infigratinib in achondroplasia demonstrating an increase in annualized height ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8941703/

Infigratinib in children with achondroplasia: the PROPEL ... The objectives of PROPEL 2 are to obtain preliminary evidence of safety and efficacy of oral infigratinib in children with achondroplasia, to identify the ...

8. paediatric-endocrinology.medwirenews.com paediatric-endocrinology.medwirenews.com/news/encouraging-oral-infigratinib-safety-and-efficacy-profile-reported-for-achondroplasia/

Encouraging oral infigratinib safety and efficacy profile ... Once daily oral treatment with infigratinib has a tolerable side effect profile and a significant positive benefit on both annualised height ...