Infigratinib for Achondroplasia

Recruiting at 12 trial locations

Overseen By QED Therapeutics Inc.

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: QED Therapeutics, a BridgeBio company

Must be taking: Vitamin D

Must not be taking: Glucocorticoids

Disqualifiers: Hypochondroplasia, Premature birth, others

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

Compensation: Varies

Number of Visits: Unknown

77 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of the drug infigratinib for children under three years old with achondroplasia, a genetic condition affecting bone growth. Researchers aim to determine the right dose and assess its efficacy. The trial includes different groups, with some receiving infigratinib and others a placebo (a harmless pill used for comparison). It is suitable for children diagnosed with achondroplasia who can swallow oral medication and meet other trial criteria. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important research.

Do I need to stop my current medications to join the trial?

The trial does not clearly state if you need to stop your current medications. However, certain medications, like those for gastroesophageal reflux disease or long-term glucocorticoid therapy, are not allowed. It's best to discuss your specific medications with the trial team.

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

Research has shown that infigratinib has been tested for safety in children with achondroplasia. Previous studies found that side effects are generally mild to moderate, and the treatment is usually well-tolerated. Some children might experience side effects, but these rarely require stopping or reducing the treatment.

One study focused on side effects that might necessitate a change or cessation of treatment. The results were positive, indicating that most children could continue without major issues. Another study demonstrated that the daily oral treatment significantly improved growth while keeping side effects manageable.

Although the current trial is in an earlier phase, previous studies in children provide encouraging evidence that infigratinib is safe. ^{1 2 3 4 5}

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

Most treatments for achondroplasia, like growth hormone therapy or limb-lengthening surgery, focus on managing symptoms rather than addressing the underlying cause. Infigratinib is unique because it targets the fibroblast growth factor receptor 3 (FGFR3) pathway, which is directly involved in the genetic mutation causing achondroplasia. This targeted approach aims to modify the disease process itself, potentially leading to more effective results. Researchers are excited about infigratinib's potential to improve growth outcomes and quality of life for individuals with achondroplasia in a way that current treatments do not.

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 children with achondroplasia grow taller. Studies have found that it significantly increases their annual growth rate. In one study, children taking a specific dose of infigratinib grew noticeably faster. The treatment was well-tolerated over 18 months, with children continuing to show growth improvements. These findings suggest that infigratinib could effectively help children with achondroplasia grow. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children under 3 years old with Achondroplasia, a bone growth disorder causing dwarfism. It's not specified who can't join the trial, but typically those with other serious health issues or allergies to the medication would be excluded.

Inclusion Criteria

Signed informed consent from parent(s) or legal guardian

Parent(s)/Guardian(s) willing and able to comply with routine care according to local guidance for ACH management

I am between 0 and 32 months old.

Exclusion Criteria

I have a condition that affects my growth.

Gestational age at birth <37 weeks and/or birth weight <2500 grams

I have recently broken a major bone or my spine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Participants receive a single ascending dose of infigratinib to evaluate safety and pharmacokinetics

4 weeks

Phase 2

Open-label portion to evaluate safety and pharmacokinetics of infigratinib

8 weeks

Phase 2b

Randomized, placebo-controlled portion to evaluate safety and efficacy of infigratinib

12 weeks

Open-label Extension

Participants may continue to receive infigratinib to assess long-term safety and efficacy until they reach 3 years old (+6 months)

Long-term

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 study tests Infigratinib, an oral medication given as minitablets or sprinkle capsules. It's a Phase 2 trial comparing Infigratinib against a placebo to assess safety and effectiveness in young children with ACH.

How Is the Trial Designed?

Group I: SAD Cohort 4 infigratinib (0 to less than 6 months old) Experimental Treatment 1 Intervention

Single Ascending Dose Escalation and PK Portion

Group II: SAD Cohort 3 infigratinib (6 months to less than 1 year old) Experimental Treatment 1 Intervention

Single Ascending Dose Escalation and PK Portion

Group III: SAD Cohort 2 infigratinib (1 to less than 2 years old) Experimental Treatment 1 Intervention

Single Ascending Dose Escalation and PK Portion

Group IV: SAD Cohort 1 infigratinib (2 to less than 3 years old) Experimental Treatment 1 Intervention

Single Ascending Dose Escalation and PK Portion

Group V: Phase 2B Cohort 3 infigratinib (0 to less than 6 months old) Experimental Treatment 1 Intervention

Randomized Safety and Efficacy Portion

Group VI: Phase 2B Cohort 2 infigratinib (6 months to less than 2 years old) Experimental Treatment 1 Intervention

Randomized Safety and Efficacy Portion

Group VII: Phase 2B Cohort 1 infigratinib (2 to less than 3 years old) Experimental Treatment 1 Intervention

Randomized Safety and Efficacy Portion

Group VIII: Phase 2 Cohort 4 infigratinib (0 to less than 6 months) Experimental Treatment 1 Intervention

Open-label Safety and PK Portion

Group IX: Phase 2 Cohort 3 infigratinib (6 months to less than 1 year old) Experimental Treatment 1 Intervention

Open-label Safety and PK Portion

Group X: Phase 2 Cohort 2 infigratinib (1 to less than 2 years old) Experimental Treatment 1 Intervention

Open-label Safety and PK Portion

Group XI: Phase 2 Cohort 1 infigratinib (2 to less than 3 years old) Experimental Treatment 1 Intervention

Open-label Safety and PK Portion

Group XII: Open- label Extension infigratinib (0 months to 3 years [+6 months old]) Experimental Treatment 1 Intervention

Open-label extension portion continuing to assess safety and efficacy in children until they reach 3 years old (+6 months)

Group XIII: Phase 2B Cohort 2 placebo (6 months to less than 2 years old) Placebo Group 1 Intervention

Randomized Safety and Efficacy study

Group XIV: Phase 2B Cohort 1 Placebo (2 to less than 3 years old) Placebo Group 1 Intervention

Randomized Safety and Efficacy study

Group XV: Phase 2B Cohort 3 Placebo (0 to less than 6 months old) Placebo Group 1 Intervention

Randomized Safety and Efficacy study

Who Is Running the Clinical Trial?

QED Therapeutics, a BridgeBio company

Lead Sponsor

QED Therapeutics, Inc., a Bridgebio company

Lead Sponsor

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/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 ...

3. 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), ...

4. 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 ...

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

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 ...