Infigratinib for Dwarfism

(HCH Trial)

Enrolling by invitation at 24 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: QED Therapeutics, Inc.

Must not be taking: Phosphorus, Calcium, Glucocorticoids, others

Disqualifiers: ACH, Malignancy, Ectopic calcification, 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 a drug called infigratinib to determine its effectiveness for children with hypochondroplasia (HCH), a form of dwarfism that results in shorter-than-average height. The research aims to assess the safety and efficacy of infigratinib at two different doses. Eligible children have participated in an earlier related study for at least 26 weeks and have been diagnosed with HCH, which causes their short stature. Participants must be able to swallow pills and stand without assistance. As a Phase 2, Phase 3 trial, this study evaluates the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that could increase serum phosphorus or calcium levels, or if you are on long-term high doses of glucocorticoids.

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

Research has shown that infigratinib has been tested in studies with children. In one study, children took infigratinib orally for up to 18 months, and it was well-tolerated. Most children did not experience major side effects and could continue the medication without serious problems. Another study found no major safety issues and noted improvements in growth rates for the children taking it. These findings suggest that infigratinib might be safe for children, but monitoring for any unexpected side effects remains important. ^{1 2 3 4 5}

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

Unlike the standard treatments for dwarfism, which often focus on growth hormone supplementation, infigratinib offers a new approach by specifically targeting the FGFR3 gene. This gene is responsible for regulating bone growth, and infigratinib's action as an FGFR inhibitor allows it to directly address the underlying genetic cause of the condition. Researchers are excited about infigratinib because it has the potential to promote bone growth more effectively and safely than existing options. Additionally, with two dosage levels being tested, it allows for flexibility in treatment to optimize results and minimize side effects.

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

Research has shown that infigratinib yields promising results in helping children with achondroplasia grow taller. Achondroplasia is a condition similar to hypochondroplasia. In one study, children who took infigratinib grew significantly faster each year. Specifically, 73% of them experienced more than a 25% increase in their growth rate after 18 months of treatment. This suggests that infigratinib might help children with dwarfism grow taller over time. Importantly, the study reported no major safety concerns, making it a hopeful option for treating conditions like hypochondroplasia. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for children with Hypochondroplasia (HCH), a form of dwarfism that affects bone growth. Participants must have completed at least 26 weeks in a prior ACCEL study and are now continuing treatment to assess further effects.

Inclusion Criteria

Participants and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures

Signed informed consent

I have been part of the QBGJ398-004 study for at least 26 weeks and am still participating.

Exclusion Criteria

Participants who have ACH or a short stature condition other than HCH

Allergy to any components of the study drug

Pregnant or breastfeeding at the screening visit or planning to become pregnant (self or partner) at any time during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 2 Treatment

Open-label treatment with infigratinib in children with hypochondroplasia, receiving either 0.128 mg/kg/day or 0.25 mg/kg/day

26 weeks

Phase 3 Treatment

Double-blind, placebo-controlled treatment with infigratinib in children with hypochondroplasia

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Infigratinib

Trial Overview The trial is testing two different doses of Infigratinib, an experimental medication, to see how effective and safe it is for treating HCH in children. It's part of a larger Phase 2/3 study following initial treatment results.

How Is the Trial Designed?

Group I: Phase 2 Cohort 2 Experimental Treatment 1 Intervention

infigratinib (0.25 mg/kg/day)

Group II: Phase 2 Cohort 1 Experimental Treatment 1 Intervention

infigratinib (0.128 mg/kg/day)

Who Is Running the Clinical Trial?

QED Therapeutics, Inc.

Lead Sponsor

Trials

11

Recruited

1,200+

QED Therapeutics, Inc., a Bridgebio company

Lead Sponsor

QED Therapeutics, a BridgeBio company

Lead Sponsor

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. bridgebio.com bridgebio.com/news/bridgebio-pharma-presents-updated-six-month-results-from-its-phase-2-cohort-5-trial-of-infigratinib-in-achondroplasia-at-the-endocrine-society-endo-2023-annual-conference/

Treatment with infigratinib at the Cohort 5 ... Treatment with infigratinib at the Cohort 5 dose level resulted in a significant and robust increase in annual height velocity (AHV), ...

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. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2411790

Oral Infigratinib Therapy in Children with Achondroplasia The primary efficacy outcome was the change from baseline in the annualized height velocity. Results. During treatment, all the children had at least one ...

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 ...

6. 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 ...

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

Positive Results from a Phase 2 Trial of Infigratinib We are encouraged by what we have seen to date, including the overall safety profile and promising initial efficacy data of infigratinib. We ...