Recruiting
Phase 2
Interventional Study of Infigratinib in Children < 3 Years Old With Achondroplasia (ACH)
Condition(s) studied
Achondroplasia
Investigational drug(s) / intervention(s)
Infigratinib is provided as a single dose of minitablets for oral administrationInfigratinib is provided as sprinkle capsules for daily oral administrationInfigratinib or placebo comparator is provided as sprinkle capsules for daily oral administrationInfigratinib is provided as sprinkle capsules for daily oral administration
Infigratinib is provided as a single dose of minitablets for oral administration: * The initial cohort dose of infigratinib will begin at the protocol-specified starting dose, with subsequent cohort escalation based on protocol specific criteria.
* The dose and number of minitablets will be calculated based on individual participant age and weight.
Infigratinib is provided as sprinkle capsules for daily oral administration: * The cohort dose of infigratinib will be the dose identified in the Single Ascending Dose portion for the age group.
* The dose and number of sprinkle capsules/day will be calculated based on individual participant age and weight. Doses will be adjusted based on age and weight changes approximately every 3 months.
Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration: * The cohort dose of infigratinib or placebo will be the dose confirmed in the Phase 2 portion for the age group.
* The dose and number of sprinkle capsules/day will be calculated based on individual participant age and weight. Doses will be adjusted based on age and weight changes approximately every 3 months.
Infigratinib is provided as sprinkle capsules for daily oral administration: * The dose of infigratinib will be the dose confirmed in the Phase 2 portion and used in the Phase 2b portion for the age group.
* The dose and number of sprinkle capsules/day will be calculated based on individual participant age and weight. Doses will be adjusted based on age and weight changes approximately every 3 months for the first year and every 6 months thereafter.
Study summary
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.
Eligibility
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.
Primary outcome measure(s)
- Single Ascending Dose Portion: Identify the dose of infigratinib to be used in each age cohort of the Phase 2 potion of the study (by assessing safety and PK of infigratinib and its active metabolites) — 2 weeks
- Phase 2 Portion: Confirm the doses to be used in each age cohort in the Phase 2b portion of the study (by assessing safety and PK of infigratinib and its active metabolites). — 52 weeks
- Phase 2b Portion: Evaluate the safety and efficacy of infigratinib in infants and children < 3 years old with ACH (by assessing AE's & SAE's) — 52 weeks
- Extension Portion: Evaluate the safety and efficacy of infigratinib in participants who completed the Phase 2 or Phase 2b portion of the study until they have reached 3 years old (+6 months) (by assessing AE's and SAE's) — 3 years and 6 months
Trial sites (12)
| Facility | City | Region | Status |
|---|
| UCSF Benioff Children's Hospital |
Oakland |
California |
Recruiting |
| Johns Hopkins University |
Baltimore |
Maryland |
Recruiting |
| University of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic |
Madison |
Wisconsin |
Recruiting |
| Murdoch Children's Research Institute |
Parkville |
Victoria |
Recruiting |
| Children's Hospital of Eastern Ontario Research Institute |
Ottawa |
Ontario |
Recruiting |
| Université de Montréal - Centre Hospitalier Universitaire Sainte-Justine |
Montreal |
Quebec |
Recruiting |
| Paediatric Clinical Research Unit at Oslo University Hospital |
Oslo |
Norway |
Recruiting |
| KK Women's and Children's Hospital |
Singapore |
Singapore |
Recruiting |
| Unidad de Cirugía Artroscópica (UCA) |
Vitoria-Gasteiz |
Spain |
Recruiting |
| NHS Greater Glasgow and Clyde |
Glasgow |
United Kingdom |
Recruiting |
| Manchester University NHS Foundation Trust |
Manchester |
United Kingdom |
Recruiting |
| Sheffield Children's NHS Foundation Trust |
Sheffield |
United Kingdom |
Recruiting |