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AchondroplasiaPhase 2NCT04265651

Study of Infigratinib in Children With Achondroplasia

A Phase 2 study testing Infigratinib 0.016 mg/kg, Infigratinib 0.032 mg/kg and Infigratinib 0.064 mg/kg in people with Achondroplasia, run by QED Therapeutics, a BridgeBio company at 19 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 3 to 11 years
Conditions the study is for
Achondroplasia
What is being tested?
Infigratinib 0.016 mg/kg, Infigratinib 0.032 mg/kg and Infigratinib 0.064 mg/kg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
19 sitesin 6 countries
Study dates
10 Mar 2020to 21 Oct 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 11 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

19 sites in 6 countries.

19 sites in 6 countries

United Kingdom6 sites
  • Birmingham Children's Hospital

    Birmingham

  • University Hospitals Bristol and Weston NHS Foundation Trust

    Bristol, BS1 3NU

  • Queen Elizabeth University Hospital

    Glasgow

  • Evelina London Children's Hospital

    London

  • Manchester University Children's Hospital

    Manchester

  • Sheffield Children's Hospital

    Sheffield, England, S10 2TH

Other trials in United Kingdom

United States5 sites
  • Johns Hopkins School of Medicine

    Baltimore, Maryland, 21211

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • UCSF Benioff Children's Hospital

    Oakland, California, 94618

  • Nemours Alfred I. Dupont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

France3 sites
  • Hopital Femme Mere Enfant

    Lyon

  • Hopital Necker-Enfants Malades

    Paris

  • Hopital des Enfants

    Toulouse

Other trials in France

Spain3 sites
  • Hospital Universitario La Paz

    Madrid, 24086

  • Hospital Universitario Virgen de la Victoria

    Málaga

  • Vithas Hospital San José

    Vitoria-Gasteiz, Álava, 01012

Other trials in Spain

Australia1 site
  • Murdoch Children's Hospital

    Parkville, Victoria, 3052

Other trials in Australia

Canada1 site
  • Stollery Children's Hospital

    Edmonton, Alberta, T6G 2H7

Other trials in Canada

About this study

Official title: Phase 2, Open-Label, Dose-Escalation and Dose-Expansion Study of Infigratinib, an FGFR 1-3-Selective Tyrosine Kinase Inhibitor, in Children With Achondroplasia: PROPEL 2

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
Being tested
Infigratinib 0.016 mg/kg, Infigratinib 0.032 mg/kg, Infigratinib 0.064 mg/kg, Infigratinib 0.128 mg/kg, Infigratinib 0.25 mg/kg
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
Medical subject headings
Achondroplasia, Mucopolysaccharidosis IV, Dwarfism, Bone Diseases, Bone Diseases, Developmental, Musculoskeletal Diseases, Osteochondrodysplasias, Genetic Diseases, Inborn

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Infigratinib 0.016 mg/kgDrug

    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/kgDrug

    Subsequent cohort dose escalation based on protocol-specific criteria.

    Infigratinib tablets to be administered by mouth.

  • Infigratinib 0.064 mg/kgDrug

    Subsequent cohort dose escalation based on protocol-specific criteria.

    Infigratinib tablets to be administered by mouth.

  • Infigratinib 0.128 mg/kgDrug

    Subsequent cohort dose escalation based on protocol-specific criteria.

    Infigratinib tablets to be administered by mouth.

  • Infigratinib 0.25 mg/kgDrug

    Subsequent cohort dose escalation based on protocol-specific criteria.

    Infigratinib tablets to be administered by mouth.

Study groups in NCT04265651
Study groupRoleWhat they receive
Infigratinib 0.016 mg/kgExperimentalDose 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.
Receives: Drug: Infigratinib 0.016 mg/kg
Infigratinib 0.032 mg/kgExperimentalDose 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.
Receives: Drug: Infigratinib 0.032 mg/kg
Infigratinib 0.064 mg/kgExperimentalDose 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.
Receives: Drug: Infigratinib 0.064 mg/kg
Infigratinib 0.128 mg/kgExperimentalDose 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.
Receives: Drug: Infigratinib 0.128 mg/kg
Infigratinib 0.25 mg/kgExperimentalDose 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.
Receives: Drug: Infigratinib 0.25 mg/kg

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 18 months

  2. Change from baseline in annualized height velocity

    Measured: Up to 18 months

  3. PK parameters of infigratinib (Cmax- PK substudy only)

    Measured: 21 days

  4. PK parameters of infigratinib (Clast- PK substudy only)

    Measured: 21 days

  5. PK parameters of infigratinib (Tmax- PK substudy only)

    Measured: 21 days

  6. PK parameters of infigratinib (AUC24- PK substudy only)

    Measured: 21 days

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

    Measured: 21 days

  8. PK parameters of infigratinib (AUCinf- PK substudy only)

    Measured: 21 days

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

    Measured: 21 days

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

    Measured: 21 days

  11. PK parameters of infigratinib (Racc- PK substudy only)

    Measured: 21 days

Secondary outcomes (12)
  1. Incidence of adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability

    Measured: Up to 18 months

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

    Measured: Up to 18 months

  3. Absolute and change from baseline in weight (kg)

    Measured: Up to 18 months

  4. Absolute and change from baseline in sitting height (cm)

    Measured: Up to 18 months

  5. Absolute and change from baseline in head circumference (cm)

    Measured: Up to 18 months

  6. Absolute and change from baseline in upper and lower arm length (cm)

    Measured: Up to 18 months

  7. Absolute and change from baseline in thigh length (cm)

    Measured: Up to 18 months

  8. Absolute and change from baseline in knee height (cm)

    Measured: Up to 18 months

  9. Absolute and change from baseline in arm span (cm)

    Measured: Up to 18 months

  10. Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)

    Measured: Up to 18 months

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

    Measured: Up to 18 months

  12. Changes in pharmacodynamic parameters by assessing collagen X marker

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2020
  2. Study start10 Mar 2020
  3. Primary completion21 Oct 2024
  4. Study completion21 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04265651
Sponsor's protocol ID
QBGJ398-201
Status last verified
Oct 2025
First submitted
29 Jan 2020
Last updated
22 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 39555818
  • 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.

    PubMed 35342457

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Infigratinib 0.016 mg/kg, Infigratinib 0.032 mg/kg and Infigratinib 0.064 mg/kg in people with Achondroplasia, run by QED Therapeutics, a BridgeBio company at 19 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United Kingdom, United States, France, Spain, Australia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation (time frame: Up to 18 months). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04265651, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2025.

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