Infigratinib treatment for children under 3 with achondroplasia

Phase 2b, Randomized, Double-Blind, Placebo-Controlled Clinical Trial, Preceded by a Single Ascending Dose Portion and a Phase 2 Open-Label Portion, to Evaluate the Safety and Efficacy of Oral Infigratinib in Infants and Young Children With Achondroplasia

This trial tests whether daily oral infigratinib helps children younger than 3 years who have achondroplasia.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 77 (estimated)
• Ages: 0 Years to 32 Months
• Sex: All
• Sponsor: QED Therapeutics, a BridgeBio company (industry)
• Drugs / interventions: infigratinib
• Locations: 13 sites (Oakland, California and 12 other locations)
• Trial ID: NCT07169279 on ClinicalTrials.gov

What this trial studies

PROPEL Infant & Toddler (I&T) is a Phase 2, multicenter, randomized, placebo-controlled program that includes a single ascending dose (SAD) portion, an open-label Phase 2 portion, a randomized placebo-controlled Phase 2b portion, and an open-label extension to study oral infigratinib in children under 3 with achondroplasia. The SAD and Phase 2 portions are used to identify and confirm a safe dose based on safety and pharmacokinetics before advancing to the placebo-controlled Phase 2b. Participants receive age-appropriate oral formulations (minitablets or sprinkle capsules) and attend regular clinic visits for safety, growth measurements, and PK sampling. Genetic confirmation of achondroplasia and caregiver ability to comply with visits and routine care are required for enrollment.

Who should consider this trial

Good fit: Ideal candidates are children under 3 years old with genetically confirmed achondroplasia whose parents or guardians can attend required visits, who can take age-appropriate oral medication, and who meet vitamin D guidance for infants under 1 year.

Not a fit: Children with other skeletal dysplasias (for example hypochondroplasia), those outside the age range, those unable to take oral medication, or those with contraindications to FGFR inhibitors are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, infigratinib could increase growth velocity and reduce some complications related to achondroplasia in very young children.

How similar studies have performed: Targeting the FGFR3 pathway to modify growth is a relatively new approach with some success from related therapies, but infigratinib use in infants with achondroplasia is novel and has limited prior pediatric data.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of ACH confirmed by genetic testing. If prospective participants had prior genetic testing, the diagnosis must be confirmed by a report from a certified laboratory, documenting the specific mutation.
* Age 0 to 32 months (2 years and 8 months) at screening.
* Signed informed consent, which must be obtained from each participant's parent(s) or legal guardian.
* Parent(s)/Guardian(s) willing and able to attend all study visits and comply with all study requirements.
* Parent(s)/Guardian(s) willing and able to comply with the routine care of the study participants according to local guidance for the management of infants and young children with ACH.
* Able to swallow age-appropriate oral medication.
* In participants \<1 year old, be compliant with recommended vitamin D supplementation of 5 10 μg/day or higher (or as recommended by country specific guidelines).

Exclusion Criteria:

* Participants who have hypochondroplasia or diagnosis of genetic condition other than ACH, or any clinical condition that can affect growth.
* Gestational age at birth \<37 weeks and/or birth weight \<2500 grams.
* Gastroesophageal reflux disease requiring prolonged treatment (\>1 week) with prohibited medications.
* Evidence of cervicomedullary compression, as defined by an Achondroplasia Foramen Magnum Score (AFMS) 4, symptomatic or asymptomatic, diagnosed during MRI done at screening or a previous MRI done at any time if the participant had not undergone decompression surgery.
* History of fracture of a long bone or spine within 6 months prior to screening.
* Any other significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib and/or would require treatment with a prohibited medication (per protocol), and/or would place the participant at high risk for poor treatment compliance or for failure to complete the study.
* Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH or short stature, including (but not limited to) r-hGH, IGF-1, CNP analog, FGF ligand trap, or treatment targeting FGFR inhibition at any time.
* Regular long-term (\>3 weeks; more than twice/year) treatment with supraphysiologic doses of glucocorticoid therapy (ie, \>15 mg/m2/day of hydrocortisone or equivalent) or treatment with glucocorticoids at anti-inflammatory doses (for over 3 weeks within 6 months of the screening visit. NOTE: Low-dose topical, inhaled, or intranasal corticosteroids are acceptable.
* Significant abnormality in screening laboratory results,
* Allergy or hypersensitivity to any components of the study drug.

Where this trial is running

Oakland, California and 12 other locations

• UCSF Benioff Children's Hospital — Oakland, California, United States (RECRUITING)
• Johns Hopkins University — Baltimore, Maryland, United States (RECRUITING)
• University of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic — Madison, Wisconsin, United States (RECRUITING)
• Murdoch Children's Research Institute — Parkville, Victoria, Australia (RECRUITING)
• Children's Hospital of Eastern Ontario Research Institute — Ottawa, Ontario, Canada (RECRUITING)
• Université de Montréal - Centre Hospitalier Universitaire Sainte-Justine — Montreal, Quebec, Canada (RECRUITING)
• Paediatric Clinical Research Unit at Oslo University Hospital — Oslo, Norway (RECRUITING)
• KK Women's and Children's Hospital — Singapore, Singapore (RECRUITING)
• Unidad de Cirugia Artroscopica (UCA) — Vitoria-Gasteiz, Spain (NOT_YET_RECRUITING)
• NHS Greater Glasgow and Clyde — Glasgow, United Kingdom (NOT_YET_RECRUITING)
• Guy's and Saint Thomas' NHS Foundation Trust — London, United Kingdom (NOT_YET_RECRUITING)
• Manchester University NHS Foundation Trust — Manchester, United Kingdom (NOT_YET_RECRUITING)
• Sheffield Children's NHS Foundation Trust — Sheffield, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: QED Therapeutics Inc.

Conditions: Achondroplasia, skeletal dysplasia, endochondral ossification, achondroplasia, ACH, Shortened proximal limbs, fibroblast growth factor receptor 3, FGFR3