Study of Infigratinib in Children With Achondroplasia

NCT04265651 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: QBGJ398-201
• Study Type: interventional
• Target: 84
• Locations: 6 countries
• Sites: 19

Brief Summary

This is a Phase 2, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, and efficacy of infigratinib, a fibroblast growth factor receptor (FGFR) 1-3-selective tyrosine kinase inhibitor, in children 3 to 11 years of age with Achondroplasia (ACH) who previously participated in the PROPEL study (Protocol QBGJ398-001) for at least 6 months. The study includes dose escalation with extended treatment, and dose expansion. The study also includes a PK Substudy to fully characterize the pharmacokinetics of infigratinib in children with ACH.

Conditions

Achondroplasia

Keywords

Skeletal dysplasia; Endochondral ossification; ACH; Shortened proximal limbs; Fibroblast growth factor receptor 3; FGFR3; Endochondral bone formation; Short-limb disproportionate dwarfism; dwarfism; Bone disease; Bone diseases, developmental; Musculoskeletal diseases; Osteochondrodysplasia; Genetic diseases, inborn; Inborn

Outcome Measures

Primary Outcomes (11)

• Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation

  Up to 18 months

• Change from baseline in annualized height velocity

  Up to 18 months

• PK parameters of infigratinib (Cmax- PK substudy only)

  21 days

• PK parameters of infigratinib (Clast- PK substudy only)

  21 days

• PK parameters of infigratinib (Tmax- PK substudy only)

  21 days

• PK parameters of infigratinib (AUC24- PK substudy only)

  21 days

• PK parameters of infigratinib (T1/2- PK substudy only)

  21 days

• PK parameters of infigratinib (AUCinf- PK substudy only)

  21 days

• PK parameters of infigratinib (CL/F- PK substudy only)

  21 days

• PK parameters of infigratinib (Vz/F- PK substudy only)

  21 days

• PK parameters of infigratinib (Racc- PK substudy only)

  21 days

Secondary Outcomes (12)

• Incidence of adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability

  Up to 18 months

• Absolute height velocity (annualized to cm/year), expressed numerically and as Z-score in relation to ACH and non-ACH tables

  Up to 18 months

• Absolute and change from baseline in weight (kg)

  Up to 18 months

• Absolute and change from baseline in sitting height (cm)

  Up to 18 months

• Absolute and change from baseline in head circumference (cm)

  Up to 18 months

Study Arms (5)

Infigratinib 0.016 mg/kg

EXPERIMENTAL

Dose Escalation: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months.

Drug: Infigratinib 0.016 mg/kg

Infigratinib 0.032 mg/kg

EXPERIMENTAL

Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months.

Drug: Infigratinib 0.032 mg/kg

Infigratinib 0.064 mg/kg

EXPERIMENTAL

Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months.

Drug: Infigratinib 0.064 mg/kg

Infigratinib 0.128 mg/kg

EXPERIMENTAL

Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months.

Drug: Infigratinib 0.128 mg/kg

Infigratinib 0.25 mg/kg

EXPERIMENTAL

Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. Dose Expansion: Upon identification of the recommended dose from all cohorts analyzed, an expansion cohort of 20 subjects may begin enrollment to further determine safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of the selected dose.

Drug: Infigratinib 0.25 mg/kg

Interventions

Infigratinib 0.016 mg/kg DRUG

Initial cohort dose of infigratinib at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.

Infigratinib 0.016 mg/kg

Infigratinib 0.032 mg/kg DRUG

Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.

Infigratinib 0.032 mg/kg

Infigratinib 0.064 mg/kg DRUG

Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.

Infigratinib 0.064 mg/kg

Infigratinib 0.128 mg/kg DRUG

Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.

Infigratinib 0.128 mg/kg

Infigratinib 0.25 mg/kg DRUG

Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.

Infigratinib 0.25 mg/kg

Eligibility Criteria

• Age: 3 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed informed consent by participant or parent(s) or legally authorized representative (LAR) and signed informed assent by the participant (when applicable).
• Diagnosis of ACH, documented clinically and confirmed by genetic testing.
• At least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398-001) before study entry.
• Ambulatory and able to stand without assistance
• Able to swallow oral medication.

You may not qualify if:

• Hypochondroplasia or short stature condition other than ACH.
• In females, having had their menarche.
• Height \< -2 or \> +2 standard deviations for age and sex based on reference tables on growth in children with ACH.
• 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 corneal or retinal disorder/keratopathy.
• History of malignancy.
• Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration.
• Treatment with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids in the previous 6 months or long-term treatment (\>3 months) at any time.
• Treatment with a C-type natriuretic peptide (CNP) analog, fibroblast growth factor (FGF) ligand trap, or treatment targeting FGFR inhibition at any time.
• Regular long-term treatment (\>3 weeks) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable).
• Treatment with any other investigational product or investigational medical device for the treatment of ACH or short stature.
• Previous limb-lengthening surgery or guided growth surgery.
• Fracture within 12 months of screening.

Sponsors & Collaborators

• QED Therapeutics, a BridgeBio company: lead

Study Sites (19)

UCSF Benioff Children's Hospital

Oakland, California, 94618, United States

Location

Nemours Alfred I. Dupont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Johns Hopkins School of Medicine

Baltimore, Maryland, 21211, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Murdoch Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2H7, Canada

Location

Hopital Femme Mere Enfant

Lyon, France

Location

Hopital Necker-Enfants Malades

Paris, France

Location

Hopital des Enfants

Toulouse, France

Location

Hospital Universitario La Paz

Madrid, 24086, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Vithas Hospital San José

Vitoria-Gasteiz, Álava, 01012, Spain

Location

Sheffield Children's Hospital

Sheffield, England, S10 2TH, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, United Kingdom

Location

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, BS1 3NU, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

Evelina London Children's Hospital

London, United Kingdom

Location

Manchester University Children's Hospital

Manchester, United Kingdom

Location

Related Publications (2)

• Savarirayan R, De Bergua JM, Arundel P, Salles JP, Saraff V, Delgado B, Leiva-Gea A, McDevitt H, Nicolino M, Rossi M, Salcedo M, Cormier-Daire V, Skae M, Kannu P, Phillips J 3rd, Saal H, Harmatz P, Candler T, Hill D, Muslimova E, Weng R, Bai Y, Raj S, Hoover-Fong J, Irving M, Rogoff D. Oral Infigratinib Therapy in Children with Achondroplasia. N Engl J Med. 2025 Feb 27;392(9):865-874. doi: 10.1056/NEJMoa2411790. Epub 2024 Nov 18.

  PMID: 39555818 DERIVED

• Savarirayan R, De Bergua JM, Arundel P, McDevitt H, Cormier-Daire V, Saraff V, Skae M, Delgado B, Leiva-Gea A, Santos-Simarro F, Salles JP, Nicolino M, Rossi M, Kannu P, Bober MB, Phillips J 3rd, Saal H, Harmatz P, Burren C, Gotway G, Cho T, Muslimova E, Weng R, Rogoff D, Hoover-Fong J, Irving M. Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies. Ther Adv Musculoskelet Dis. 2022 Mar 21;14:1759720X221084848. doi: 10.1177/1759720X221084848. eCollection 2022.

  PMID: 35342457 DERIVED

MeSH Terms

Conditions

Achondroplasia; Mucopolysaccharidosis IV; Dwarfism; Bone Diseases; Bone Diseases, Developmental; Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn

Interventions

infigratinib

Condition Hierarchy (Ancestors)

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

Study Officials

• QED Therapeutics VP, Clinical Development

  QED Therapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: February 11, 2020
• Study Start: March 10, 2020
• Primary Completion: October 21, 2024
• Study Completion: October 21, 2024
• Last Updated: October 22, 2025

Record last verified: 2025-10

Locations

GB (6); US (5); AU (1); FR (3); CA (1); ES (3)