Infigratinib for Dwarfism

(HCH Trial)

Recruiting at 21 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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

ACCEL2/3 is a Phase 2/3 study. The purpose of the Phase 2 portion of the study (ACCEL2/3) is to evaluate the efficacy and safety, of infigratinib in children with hypochondroplasia (HCH) receiving infigratinib, at one of two doses, of who have completed at least 26 weeks of participation in QED-sponsored ACCEL (QBGJ398-004).

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.

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

Research shows that Infigratinib, a drug that targets specific growth factor receptors, has been effective in improving bone growth in animal models of achondroplasia, a common form of dwarfism. This suggests it may help counteract the overactivity of growth factor receptors that cause the condition. ^{1 2 3 4 5}

Is Infigratinib safe for humans?

Infigratinib has been studied in animals and humans, and while it shows promise for treating conditions like achondroplasia, high doses in animal studies have affected tooth development. This suggests that while it may be safe at certain doses, higher doses could have side effects. ^{1 2 3 6 7}

How does the drug Infigratinib differ from other treatments for dwarfism?

Infigratinib is unique because it directly targets the overactive FGFR3 gene, which is responsible for achondroplasia, a common form of dwarfism. Unlike most treatments that only address symptoms, Infigratinib is an oral medication that aims to counteract the underlying genetic cause of the condition. ^{1 2 3 6 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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. Pakistan pubmed.ncbi.nlm.nih.gov

Effects of high-dose recombinant human growth hormone treatment on IGF-1 and IGFBP-3 levels in idiopathic dwarfism patients. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

5. Norway pubmed.ncbi.nlm.nih.gov

Pre- and postnatal growth failure with microcephaly due to two novel heterozygous IGF1R mutations and response to growth hormone treatment. [2022]

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

FGFR3 targeting strategies for achondroplasia. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Endocrine assessment, molecular characterization and treatment of growth hormone insensitivity disorders. [2022]

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

Clinical and functional characterization of a patient carrying a compound heterozygous pericentrin mutation and a heterozygous IGF1 receptor mutation. [2021]