An Interventional Study of Infigratinib in Children With Hypochondroplasia

NCT06873035 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 1 other identifier: QBGJ398-304
• Study Type: interventional
• Target: 24
• Locations: 10 countries
• Sites: 22

Brief Summary

ACCEL2/3 is a Phase 2/3 study. The purpose of the Phase 2 portion of the study (ACCEL2/3) is to evaluate the efficacy and safety, of infigratinib in children with hypochondroplasia (HCH) receiving infigratinib, at one of two doses, of who have completed at least 26 weeks of participation in QED-sponsored ACCEL (QBGJ398-004).

Conditions

Hypochondroplasia

Keywords

skeletal dysplasia; endochondral ossification; hypochondroplasia; HCH; shortened proximal limbs; fibroblast growth factor receptor 3; FGFR3; endochondral bone formation; disproportionate short stature; quality of life; dwarfism; bone diseases; musculoskeletal diseases; osteochondrodysplasia; functional abilities; annualized growth velocity; annualized height velocity; growth; genetic diseases; congenital; AHV; AGV; Pathogenic variants

Outcome Measures

Primary Outcomes (2)

• Change from baseline (BL) in Annualized Height Velocity (AHV; cm/year)

  26 weeks

• Incidence, severity, and seriousness of adverse events (AEs) that require dose reduction or discontinuation

  at least 26 weeks

Secondary Outcomes (6)

• Change from BL in height Z-score (in relation to both HCH and average height tables)

  52 weeks

• Change from BL in upper to lower body segment ratio (cm)

  52 weeks

• Changes in cognitive function (as assessed by age appropriate computerized tests)

  52 weeks

• Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)

  52 weeks

• Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)

  52 weeks

Other Outcomes (3)

• Change from BL in comorbidities associated with HCH

  52 weeks

• Change from BL in Health-related Quality of Life (HRQoL) (as assessed by Pediatric Quality of Life Inventory [PedsQL tool])

  52 weeks

• Evaluate treatment benefit as assessed by qualitative interviews

  52 weeks

Study Arms (2)

Phase 2 Cohort 1

EXPERIMENTAL

infigratinib (0.128 mg/kg/day)

Drug: infigratinib 0.128 mg/kg/day

Phase 2 Cohort 2

EXPERIMENTAL

infigratinib (0.25 mg/kg/day)

Drug: infigratinib 0.25 mg/kg/day

Interventions

infigratinib 0.128 mg/kg/day DRUG

Oral infigratinib 0.128 mg/kg/day

Phase 2 Cohort 1

infigratinib 0.25 mg/kg/day DRUG

Oral infigratinib 0.25 mg/kg/day

Phase 2 Cohort 2

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must have completed at least 26 weeks and still be on the observational study (QBGJ398-004).
• Phase 2 portion: Participants 5-11 years of age (inclusive).
• Phase 3 portion: Participants 3 to \<18 years of age at screening with growth potential
• Diagnosis of HCH documented clinically by the presence of disproportionate short stature and confirmed with a molecular test.
• Participants are able to swallow oral medication.
• Participants and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures.
• Participants are ambulatory and able to stand without assistance. Sex and Contraceptive/Barrier Requirements
• Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
• If sexually active, participants whether male or female, must be willing to use a highly effective method of contraception, as relevant, while taking study drug and for 1 month after the last dose of study drug.
• Signed informed consent.

You may not qualify if:

• Participants who have ACH or a short stature condition other than HCH.
• Significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib.
• Current evidence of clinically significant corneal or retinal disorder/keratopathy confirmed by ophthalmic examination.
• Concurrent circumstance, disease, or condition that, in the view of the investigator and/or sponsor, would interfere with study participation or safety evaluations.
• History and/or current evidence of extensive ectopic tissue calcification.
• History of malignancy.
• Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH, HCH, or short stature.
• Regular long-term treatment (≥3 weeks) with supraphysiologic doses of glucocorticoid.
• Previous limb-lengthening surgery at any time or planned/expected to have limb-lengthening or guided growth surgery while participating in the study.
• Participants receiving medications which could increase serum phosphorus and/or calcium concentrations
• Clinically significant abnormality in any laboratory test result at screening.
• Pregnant or breastfeeding at the screening visit or planning to become pregnant (self or partner) at any time during the study.
• Allergy to any components of the study drug.
• Concurrent circumstance, disease, or condition that would interfere with study participation.

Sponsors & Collaborators

• QED Therapeutics, a BridgeBio company: lead

Study Sites (22)

UCSF Benioff Children's Hospital

Oakland, California, 94609, United States

Location

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Johns Hopkins School of Medicine

Baltimore, Maryland, 21287, United States

Location

University of Missouri

Columbia, Missouri, 65201, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic

Madison, Wisconsin, 53705, United States

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

London Health Services Center - Children's Hospital of Western Ontario

London, Ontario, N6C 2R5, Canada

Location

Children's Hospital of Eastern Ontario Research Institute

Ottawa, Ontario, K1H 8L1, Canada

Location

Université de Montréal - Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Hôpital Femme Mère Enfant

Bron, France, 69677, France

Location

Hôpital Universitaire Necker-Enfants Malades

Paris, France, 75015, France

Location

Centre Hospitalier Universitaire (CHU) de Toulouse - Hôpital des Enfants

Toulouse, France, 31059, France

Location

Haukeland University Hospital

Bergen, Norway, 5021, Norway

Location

Paediatric Clinical Research Unit at Osla University Hospital

Oslo, Norway, 0372, Norway

Location

Hospital Pediátrico de Coimbra

Coimbra, Portugal, 3000-602, Portugal

Location

KK Women's and Children's Hospital

Singapore, Singapore, 229899, Singapore

Location

Hospital Vithas San Jose

Vitoria-Gasteiz, Spain, 01008, Spain

Location

Astrid Lindgren Children's Hospital

Solna, Sweden, 17164, Sweden

Location

Manchester University

Manchester, United Kingdom, M13 9WL, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, United Kingdom, S10 2TH, United Kingdom

Location

MeSH Terms

Conditions

Hypochondroplasia; Mucopolysaccharidosis IV; Dwarfism; Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn

Interventions

infigratinib

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Bone Diseases, Developmental; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study comprises an open-label Phase 2 portion to evaluate safety and efficacy in participants receiving infigratinib at one of two doses followed by a Phase 3 randomized, double-blind portion of the dose selected from the Phase 2 portion versus placebo.

Study Record Dates

• First Submitted: February 18, 2025
• First Posted: March 12, 2025
• Study Start: April 22, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); SG (1); ES (1); CA (3); NO (2); PT (1); FR (3); GB (2); US (7); SE (1)