A Study to Evaluate the Efficacy and Safety of Infigratinib in Children and Adolescents With Achondroplasia

NCT06164951 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: QBGJ398-303
• Study Type: interventional
• Target: 114
• Locations: 10 countries
• Sites: 27

Brief Summary

This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of infigratinib in children and adolescents with achondroplasia (ACH) who have completed at least 26 weeks of participation in the QED-sponsored study PROPEL (QBGJ398-001).

Conditions

Achondroplasia

Keywords

Skeletal dysplasia; Endochondral ossification; Quality of life in achondroplasia; Fibroblast growth factor receptor 3; FGFR3; Endochondral bone formation; Short-limb disproportionate dwarfism; Dwarfism; Bone disease; Functionality in achondroplasia; Musculoskeletal diseases; Osteochondrodysplasia; Genetic diseases; Long-term treatment; Growth; Annualized height velocity

Outcome Measures

Primary Outcomes (1)

• Change from baseline (BL) in annualized height velocity (cm/year)

  Week 52

Secondary Outcomes (20)

• Change from BL in height Z-score (in relation to ACH tables)

  Week 52

• Change from BL in upper to lower body segment ratio

  Week 52

• Change from BL in height Z-score (in relation to non-ACH tables)

  Week 52

• Annualized height velocity (cm/year)

  Week 52

• Absolute and change from baseline in upper arm to forearm length ratio (cm)

  Week 52

Study Arms (2)

Infigratinib 0.25 mg/kg/day

EXPERIMENTAL

Infigratinib at 2, 3.5, 5, 7, 10 mg

Drug: Infigratinib 0.25 mg/kg/day

Placebo 0.25 mg/kg/day

PLACEBO COMPARATOR

Placebo Comparator at 2, 3.5, 5, 7, 10 mg

Drug: Placebo Comparator 0.25 mg/kg/day

Interventions

Placebo Comparator 0.25 mg/kg/day DRUG

Daily doses of oral Placebo Comparator (sprinkle capsules) at 2, 3.5, 5, 7, 10 mg

Placebo 0.25 mg/kg/day

Infigratinib 0.25 mg/kg/day DRUG

Daily doses of oral Infigratinib (sprinkle capsules) at 2, 3.5, 5, 7, 10 mg

Infigratinib 0.25 mg/kg/day

Eligibility Criteria

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

You may qualify if:

• Subject must be 3 to \<18 years of age at screening with growth potential defined as annualized height velocity of \>1.5 cm/year over a period of at least 6 months of participation in the PROPEL observational study (QBGJ398-001), pubertal Tanner stage ≤4, and bone age ≤13 years in females and ≤15 years in males.
• Type of Subject and Disease Characteristics
• Subjects who have a diagnosis of ACH that has been documented clinically and confirmed by genetic testing.
• Subjects must have completed at least 26 weeks in the PROPEL (QBGJ398-001) study before screening.
• Subjects are able to swallow oral medication.
• Subjects and parent(s), legal guardian(s), or caregivers are willing and able to comply with study visits and study procedures.
• Subjects 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, subjects, whether male or female, must be willing to use a highly effective method of contraception while taking study drug and for 3 months after the last dose of study drug.
• Informed Consent
• Signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol, must be obtained for each subject from their parent(s) or legal guardian and signed informed consent/assent must be obtained from the subject (when applicable)

You may not qualify if:

• Medical Conditions
• Subjects who have hypochondroplasia or short stature condition other than 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 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 and/or would require treatment with a prohibited medication, and/or would place the subject at high risk for poor treatment compliance or for not completing the study.
• History and/or current evidence of extensive ectopic tissue calcification.
• History of malignancy.
• Prior/Concomitant Therapy
• Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH or short stature.
• Regular long-term treatment (≥3 weeks) with supraphysiologic doses of glucocorticoid therapy (ie, \>15 mg/m2/day of hydrocortisone or equivalent) or treatment with glucocorticoids at anti-inflammatory doses (ie, 2.5-10 mg/kg/day of hydrocortisone or equivalent) for over 3 weeks within 6 months of the screening visit (low-dose local preparations including inhaled steroid for asthma, intranasal sprays for allergies, and topical steroids are allowed).
• Previous limb-lengthening surgery at any time or planned/expected to have limb-lengthening surgery or guided growth surgery during the study period. Guided growth surgery with plates removed at least 12 months prior to screening is allowed.
• Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 or prolonged treatment (\>1 week) with medications that alter the pH of the gastrointestinal tract including antacids, H2 antagonists (eg, ranitidine, famotidine), and proton-pump inhibitors (eg, omeprazole).
• Current evidence of endocrine alterations of calcium/phosphorus homeostasis.
• Diagnostic assessments
• Subjects who have significant abnormality in screening laboratory results.

Sponsors & Collaborators

• QED Therapeutics, a BridgeBio company: lead

Study Sites (27)

QED Investigative Site

San Francisco, California, 94609, United States

Location

QED Investigative Site

Aurora, Colorado, 80045, United States

Location

QED Investigative Site

Baltimore, Maryland, 21287, United States

Location

QED Investigative Site

Columbia, Missouri, 65212, United States

Location

QED Investigative Site

Cincinnati, Ohio, 45229, United States

Location

QED Investigative Site

Nashville, Tennessee, 37232, United States

Location

QED Investigative Site

Madison, Wisconsin, 53792, United States

Location

QED Investigative Site

Buenos Aires, Buenos Aires F.D., C1245AAM, Argentina

Location

QED Investigative Site

Parkville, Victoria, 3052, Australia

Location

QED Investigative Site

Edmonton, Alberta, T6G 2B7, Canada

Location

QED Investigative Site

London, Ontario, N6A 5W9, Canada

Location

QED Investigative Site

Ottawa, Ontario, K1H 8L1, Canada

Location

QED Investigative Site

Montreal, Quebec, H3T 1C5, Canada

Location

QED Investigative Site

Bron, 69677, France

Location

QED Investigative Site

Paris, 75015, France

Location

QED Investigative Site

Toulouse, 31059, France

Location

QED Investigative Site

Rome, 00168, Italy

Location

QED Investigative Site

Bergen, 5009, Norway

Location

QED Investigative Site

Oslo, 0372, Norway

Location

QED Investigative Site

Singapore, 229899, Singapore

Location

QED Investigative Site

Málaga, 29010, Spain

Location

QED Investigative Site

Vitoria-Gasteiz, 01008, Spain

Location

QED Investigative Site

Bristol, BS2 8BJ, United Kingdom

Location

QED Investigative Site

Glasgow, G51 4TF, United Kingdom

Location

QED Investigative Site

London, SE1 7EH, United Kingdom

Location

QED Investigative Site

Manchester, M13 9WL, United Kingdom

Location

QED Investigative Site

Sheffield, S10 2TH, United Kingdom

Location

MeSH Terms

Conditions

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

Interventions

infigratinib

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; 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, Inc. Medical Director, Clinical Development

  QED Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: December 11, 2023
• Study Start: November 10, 2023
• Primary Completion: December 18, 2025
• Study Completion: December 18, 2025
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2); SG (1); AR (1); CA (4); US (7); GB (5); FR (3); ES (2); AU (1); IT (1)