Study of Infigratinib in Children With Achondroplasia

NCT ID: NCT04265651

Last Updated: 2025-10-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-10

Study Completion Date

2024-10-21

Brief Summary

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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.

Detailed Description

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Conditions

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Achondroplasia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Infigratinib 0.016 mg/kg

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.

Group Type EXPERIMENTAL

Infigratinib 0.016 mg/kg

Intervention Type 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 0.032 mg/kg

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.

Group Type EXPERIMENTAL

Infigratinib 0.032 mg/kg

Intervention Type DRUG

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Infigratinib 0.064 mg/kg

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.

Group Type EXPERIMENTAL

Infigratinib 0.064 mg/kg

Intervention Type DRUG

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Infigratinib 0.128 mg/kg

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.

Group Type EXPERIMENTAL

Infigratinib 0.128 mg/kg

Intervention Type DRUG

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Infigratinib 0.25 mg/kg

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.

Group Type EXPERIMENTAL

Infigratinib 0.25 mg/kg

Intervention Type DRUG

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Interventions

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Infigratinib 0.016 mg/kg

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.

Intervention Type DRUG

Infigratinib 0.032 mg/kg

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Intervention Type DRUG

Infigratinib 0.064 mg/kg

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Intervention Type DRUG

Infigratinib 0.128 mg/kg

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Intervention Type DRUG

Infigratinib 0.25 mg/kg

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Hypochondroplasia or short stature condition other than ACH.
2. In females, having had their menarche.
3. Height \< -2 or \> +2 standard deviations for age and sex based on reference tables on growth in children with ACH.
4. Significant concurrent disease or condition that, in the view of the Investigator and/or Sponsor, would confound assessment of efficacy or safety of infigratinib.
5. Current evidence of corneal or retinal disorder/keratopathy.
6. History of malignancy.
7. Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration.
8. 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.
9. Treatment with a C-type natriuretic peptide (CNP) analog, fibroblast growth factor (FGF) ligand trap, or treatment targeting FGFR inhibition at any time.
10. Regular long-term treatment (\>3 weeks) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable).
11. Treatment with any other investigational product or investigational medical device for the treatment of ACH or short stature.
12. Previous limb-lengthening surgery or guided growth surgery.
13. Fracture within 12 months of screening.
Minimum Eligible Age

3 Years

Maximum Eligible Age

11 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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QED Therapeutics, Inc., a Bridgebio company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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QED Therapeutics VP, Clinical Development

Role: STUDY_DIRECTOR

QED Therapeutics

Locations

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UCSF Benioff Children's Hospital

Oakland, California, United States

Site Status

Nemours Alfred I. Dupont Hospital for Children

Wilmington, Delaware, United States

Site Status

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Murdoch Children's Hospital

Parkville, Victoria, Australia

Site Status

Stollery Children's Hospital

Edmonton, Alberta, Canada

Site Status

Hopital Femme Mere Enfant

Lyon, , France

Site Status

Hopital Necker-Enfants Malades

Paris, , France

Site Status

Hopital des Enfants

Toulouse, , France

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Vithas Hospital San José

Vitoria-Gasteiz, Álava, Spain

Site Status

Sheffield Children's Hospital

Sheffield, England, United Kingdom

Site Status

Birmingham Children's Hospital

Birmingham, , United Kingdom

Site Status

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, , United Kingdom

Site Status

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

Evelina London Children's Hospital

London, , United Kingdom

Site Status

Manchester University Children's Hospital

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Canada France Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39555818 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35342457 (View on PubMed)

Other Identifiers

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QBGJ398-201

Identifier Type: -

Identifier Source: org_study_id

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