Interventional Study of Infigratinib in Children < 3 Years Old With Achondroplasia (ACH)
Purpose
This is a Phase 2, multicenter, randomized, placebo-controlled study to evaluate the safety and efficacy of infigratinib in participants < 3 years old with ACH. The purposes of the SAD and Phase 2 portions are to identify and confirm the dose of infigratinib to be used in the Phase 2b portion, based on safety and PK. The purpose of the Phase 2b, placebo-controlled portion is to evaluate the safety and efficacy of infigratinib in children < 3 years old with ACH at the selected dose.
Condition
- Achondroplasia
Eligibility
- Eligible Ages
- Between 0 Years and 32 Months
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- This study comprises 4 portions: a Single Ascending Dose (SAD) portion and open-label Phase 2 portion to evaluate safety and PK and select a dose level for Phase 2b; a placebo-controlled Phase 2b portion, to assess safety and efficacy at the selected dose level; and an open-label extension portion to evaluate safety and efficacy in children < 3 years old who have completed the Phase 2 or Phase 2b portion of the study.
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental SAD Cohort 1 infigratinib (2 to less than 3 years old) |
Single Ascending Dose Escalation and PK Portion |
|
|
Experimental SAD Cohort 2 infigratinib (1 to less than 2 years old) |
Single Ascending Dose Escalation and PK Portion |
|
|
Experimental SAD Cohort 3 infigratinib (6 months to less than 1 year old) |
Single Ascending Dose Escalation and PK Portion |
|
|
Experimental SAD Cohort 4 infigratinib (0 to less than 6 months old) |
Single Ascending Dose Escalation and PK Portion |
|
|
Experimental Phase 2 Cohort 1 infigratinib (2 to less than 3 years old) |
Open-label Safety and PK Portion |
|
|
Experimental Phase 2 Cohort 2 infigratinib (1 to less than 2 years old) |
Open-label Safety and PK Portion |
|
|
Experimental Phase 2 Cohort 3 infigratinib (6 months to less than 1 year old) |
Open-label Safety and PK Portion |
|
|
Experimental Phase 2 Cohort 4 infigratinib (0 to less than 6 months) |
Open-label Safety and PK Portion |
|
|
Experimental Phase 2B Cohort 1 infigratinib (2 to less than 3 years old) |
Randomized Safety and Efficacy Portion |
|
|
Experimental Phase 2B Cohort 2 infigratinib (6 months to less than 2 years old) |
Randomized Safety and Efficacy Portion |
|
|
Experimental Phase 2B Cohort 3 infigratinib (0 to less than 6 months old) |
Randomized Safety and Efficacy Portion |
|
|
Experimental Open- label Extension infigratinib (0 months to 3 years [+6 months old]) |
Open-label extension portion continuing to assess safety and efficacy in children until they reach 3 years old (+6 months) |
|
|
Placebo Comparator Phase 2B Cohort 1 Placebo (2 to less than 3 years old) |
Randomized Safety and Efficacy study |
|
|
Placebo Comparator Phase 2B Cohort 2 placebo (6 months to less than 2 years old) |
Randomized Safety and Efficacy study |
|
|
Placebo Comparator Phase 2B Cohort 3 Placebo (0 to less than 6 months old) |
Randomized Safety and Efficacy study |
|
Recruiting Locations
UCSF Benioff Children's Hospital
Oakland, California 94609
Oakland, California 94609
Johns Hopkins University
Baltimore, Maryland 21218
Baltimore, Maryland 21218
University of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic
Madison, Wisconsin 53705
Madison, Wisconsin 53705
More Details
- Status
- Recruiting
- Sponsor
- QED Therapeutics, a BridgeBio company
Detailed Description
PROPEL Infant & Toddler (I&T) is a Phase 2, multicenter, randomized, placebo-controlled study that comprises 4 portions: the single ascending dose (SAD) portion (open-label), the Phase 2 portion (open-label), the Phase 2b portion (placebo-controlled), and an Extension Portion (open-label). The study will evaluate children with ACH < 3 years old being administered oral infigratinib.