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Study of Infigratinib in Children With Achondroplasia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04265651
Recruitment Status : Recruiting
First Posted : February 11, 2020
Last Update Posted : February 8, 2023
Sponsor:
Information provided by (Responsible Party):
QED Therapeutics, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Achondroplasia Drug: Infigratinib 0.016 mg/kg Drug: Infigratinib 0.032 mg/kg Drug: Infigratinib 0.064 mg/kg Drug: Infigratinib 0.128 mg/kg Drug: Infigratinib 0.25 mg/kg Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 10, 2020
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.

 Drug: 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.
Experimental: 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.

 Drug: Infigratinib 0.032 mg/kg

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.
Experimental: 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.

 Drug: Infigratinib 0.064 mg/kg

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.
Experimental: 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.

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 0.128 mg/kg

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.
Experimental: 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.

 Drug: Infigratinib 0.25 mg/kg

Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation [ Time Frame: Up to 18 months ]
  2. Change from baseline in annualized height velocity [ Time Frame: Up to 18 months ]
  3. PK parameters of infigratinib (Cmax- PK substudy only) [ Time Frame: 21 days ]
  4. PK parameters of infigratinib (Clast- PK substudy only) [ Time Frame: 21 days ]
  5. PK parameters of infigratinib (Tmax- PK substudy only) [ Time Frame: 21 days ]
  6. PK parameters of infigratinib (AUC24- PK substudy only) [ Time Frame: 21 days ]
  7. PK parameters of infigratinib (T1/2- PK substudy only) [ Time Frame: 21 days ]
  8. PK parameters of infigratinib (AUCinf- PK substudy only) [ Time Frame: 21 days ]
  9. PK parameters of infigratinib (CL/F- PK substudy only) [ Time Frame: 21 days ]
  10. PK parameters of infigratinib (Vz/F- PK substudy only) [ Time Frame: 21 days ]
  11. PK parameters of infigratinib (Racc- PK substudy only) [ Time Frame: 21 days ]

Secondary Outcome Measures :
  1. Incidence of adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability [ Time Frame: 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 [ Time Frame: Up to 18 months ]
  3. Absolute and change from baseline in weight (kg) [ Time Frame: Up to 18 months ]
  4. Absolute and change from baseline in sitting height (cm) [ Time Frame: Up to 18 months ]
  5. Absolute and change from baseline in head circumference (cm) [ Time Frame: Up to 18 months ]
  6. Absolute and change from baseline in upper and lower arm length (cm) [ Time Frame: Up to 18 months ]
  7. Absolute and change from baseline in thigh length (cm) [ Time Frame: Up to 18 months ]
  8. Absolute and change from baseline in knee height (cm) [ Time Frame: Up to 18 months ]
  9. Absolute and change from baseline in arm span (cm) [ Time Frame: Up to 18 months ]
  10. Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax) [ Time Frame: Up to 18 months ]
  11. Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax) [ Time Frame: Up to 18 months ]
  12. Changes in pharmacodynamic parameters by assessing collagen X marker [ Time Frame: Up to 18 months ]
  13. Changes in pharmacodynamic parameters by assessing serum type 1 collagen c-telopeptide [ Time Frame: Up to 18 months ]
  14. Changes in pharmacodynamic parameters by assessing procollagen type 1 N-telopeptide [ Time Frame: Up to 18 months ]
  15. Changes in pharmacodynamic parameters by assessing bone-specific alkaline phosphatase [ Time Frame: Up to 18 months ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04265651


Contacts
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Contact: QED Therapeutics VP, Clinical Development 1-877-280-5655 PROPELstudyinfo@QEDTX.com

Locations
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Sponsors and Collaborators
QED Therapeutics, Inc.
Investigators
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Study Director: QED Therapeutics VP, Clinical Development QED Therapeutics
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: QED Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04265651    
Other Study ID Numbers: QBGJ398-201
First Posted: February 11, 2020    Key Record Dates
Last Update Posted: February 8, 2023
Last Verified: February 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by QED Therapeutics, Inc.:
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
Additional relevant MeSH terms:
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Achondroplasia
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
 Osteochondrodysplasias
Genetic Diseases, Inborn
Infigratinib
Antineoplastic Agents