Interventional Study of Infigratinib in Children < 3 Years Old With Achondroplasia (ACH)

NCT07169279 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: QBGJ398-204
• Study Type: interventional
• Target: 77
• Locations: 7 countries
• Sites: 13

Brief 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.

Conditions

Achondroplasia

Keywords

skeletal dysplasia; endochondral ossification; achondroplasia; ACH; Shortened proximal limbs; fibroblast growth factor receptor 3; FGFR3; encodhondral bone formation; disproportionate short stature; quality of life; dwarfism; bone diseases; musculoskeletal diseases; osteochondrodysplasia; functional abilities; annualized growth velocity; annualized height velocity; growth; growth disorder; congenital; AHV; AGV; infant and toddler

Outcome Measures

Primary Outcomes (4)

• 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

Secondary Outcomes (39)

• Phase 2: Evaluate the safety of oral daily doses of infigratinib (by assessing AEs and SAEs)

  52 weeks

• Phase 2: Evaluate changes in indicators of growth (by assessing change from BL in body length z-score at Week 52 in relation to ACH tables)

  52 weeks

• Phase 2: Evaluate changes in indicators of body proportions (by assessing change from BL to Week 52 in upper-to-lower body segment ratio and head circumference/body length ratio)

  52 weeks

• Phase 2: Change from BL in Health-related Quality of Life (HRQoL) (as assessed by Infant and Toddler Quality of Life Inventory [ITQoL] tool)

  52 weeks

• Phase 2: Milestone Development of motor skills (assessed with development milestone charts)

  52 weeks

Study Arms (15)

SAD Cohort 1 infigratinib (2 to less than 3 years old)

EXPERIMENTAL

Single Ascending Dose Escalation and PK Portion

Drug: Infigratinib is provided as a single dose of minitablets for oral administration

SAD Cohort 2 infigratinib (1 to less than 2 years old)

EXPERIMENTAL

Single Ascending Dose Escalation and PK Portion

Drug: Infigratinib is provided as a single dose of minitablets for oral administration

SAD Cohort 3 infigratinib (6 months to less than 1 year old)

EXPERIMENTAL

Single Ascending Dose Escalation and PK Portion

Drug: Infigratinib is provided as a single dose of minitablets for oral administration

SAD Cohort 4 infigratinib (0 to less than 6 months old)

EXPERIMENTAL

Single Ascending Dose Escalation and PK Portion

Drug: Infigratinib is provided as a single dose of minitablets for oral administration

Phase 2 Cohort 1 infigratinib (2 to less than 3 years old)

EXPERIMENTAL

Open-label Safety and PK Portion

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2 Cohort 2 infigratinib (1 to less than 2 years old)

EXPERIMENTAL

Open-label Safety and PK Portion

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2 Cohort 3 infigratinib (6 months to less than 1 year old)

EXPERIMENTAL

Open-label Safety and PK Portion

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2 Cohort 4 infigratinib (0 to less than 6 months)

EXPERIMENTAL

Open-label Safety and PK Portion

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 1 infigratinib (2 to less than 3 years old)

EXPERIMENTAL

Randomized Safety and Efficacy Portion

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 2 infigratinib (6 months to less than 2 years old)

EXPERIMENTAL

Randomized Safety and Efficacy Portion

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 3 infigratinib (0 to less than 6 months old)

EXPERIMENTAL

Randomized Safety and Efficacy Portion

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Open- label Extension infigratinib (0 months to 3 years [+6 months old])

EXPERIMENTAL

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

Drug: Infigratinib is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 1 Placebo (2 to less than 3 years old)

PLACEBO COMPARATOR

Randomized Safety and Efficacy study

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 2 placebo (6 months to less than 2 years old)

PLACEBO COMPARATOR

Randomized Safety and Efficacy study

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Phase 2B Cohort 3 Placebo (0 to less than 6 months old)

PLACEBO COMPARATOR

Randomized Safety and Efficacy study

Drug: Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration

Interventions

Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration DRUG

* 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.

Phase 2B Cohort 1 Placebo (2 to less than 3 years old); Phase 2B Cohort 1 infigratinib (2 to less than 3 years old); Phase 2B Cohort 2 infigratinib (6 months to less than 2 years old); Phase 2B Cohort 2 placebo (6 months to less than 2 years old); Phase 2B Cohort 3 Placebo (0 to less than 6 months old); Phase 2B Cohort 3 infigratinib (0 to less than 6 months old)

Infigratinib is provided as sprinkle capsules for daily oral administration DRUG

* 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.

Phase 2 Cohort 1 infigratinib (2 to less than 3 years old); Phase 2 Cohort 2 infigratinib (1 to less than 2 years old); Phase 2 Cohort 3 infigratinib (6 months to less than 1 year old); Phase 2 Cohort 4 infigratinib (0 to less than 6 months)

Infigratinib is provided as a single dose of minitablets for oral administration DRUG

* The initial cohort dose of infigratinib will begin at the protocol-specified starting dose, with subsequent cohort escalation based on protocol specific criteria. * The target dose is the dose that will provide similar exposure to the dose of 0.25 mg/kg/day in participants 3 years old and older. * The dose and number of minitablets will be calculated based on individual participant age and weight.

SAD Cohort 1 infigratinib (2 to less than 3 years old); SAD Cohort 2 infigratinib (1 to less than 2 years old); SAD Cohort 3 infigratinib (6 months to less than 1 year old); SAD Cohort 4 infigratinib (0 to less than 6 months old)

Eligibility Criteria

• Age: 0 Years - 32 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• QED Therapeutics, a BridgeBio company: lead

Study Sites (13)

UCSF Benioff Children's Hospital

Oakland, California, 94609, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21218, United States

RECRUITING

University of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic

Madison, Wisconsin, 53705, United States

RECRUITING

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

RECRUITING

Children's Hospital of Eastern Ontario Research Institute

Ottawa, Ontario, K1H 8L1, Canada

RECRUITING

Université de Montréal - Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

Paediatric Clinical Research Unit at Oslo University Hospital

Oslo, 0372, Norway

RECRUITING

KK Women's and Children's Hospital

Singapore, 2298899, Singapore

RECRUITING

Unidad de Cirugia Artroscopica (UCA)

Vitoria-Gasteiz, 01010, Spain

NOT YET RECRUITING

NHS Greater Glasgow and Clyde

Glasgow, G3 8SJ, United Kingdom

NOT YET RECRUITING

Guy's and Saint Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

NOT YET RECRUITING

Manchester University NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

NOT YET RECRUITING

Sheffield Children's NHS Foundation Trust

Sheffield, S10 2TH, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Achondroplasia; Mucopolysaccharidosis IV; Dwarfism; Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Growth Disorders

Interventions

Administration, Oral; infigratinib

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

QED Therapeutics Inc.

CONTACT

18772805655; medinfo@qedtx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 23, 2025
• First Posted: September 11, 2025
• Study Start: November 19, 2025
• Primary Completion (Estimated): March 1, 2032
• Study Completion (Estimated): March 1, 2032
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1); US (3); AU (1); NO (1); ES (1); GB (4); CA (2)