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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04265651




Registration number
NCT04265651
Ethics application status
Date submitted
29/01/2020
Date registered
11/02/2020

Titles & IDs
Public title
Study of Infigratinib in Children with Achondroplasia
Scientific 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
Secondary ID [1] 0 0
QBGJ398-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Achondroplasia 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Infigratinib 0.016 mg/kg
Treatment: Drugs - Infigratinib 0.032 mg/kg
Treatment: Drugs - Infigratinib 0.064 mg/kg
Treatment: Drugs - Infigratinib 0.128 mg/kg
Treatment: Drugs - Infigratinib 0.25 mg/kg

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.

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.

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.

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.

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: Infigratinib 0.032 mg/kg
Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Treatment: Drugs: Infigratinib 0.064 mg/kg
Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Treatment: Drugs: Infigratinib 0.128 mg/kg
Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.

Treatment: Drugs: Infigratinib 0.25 mg/kg
Subsequent cohort dose escalation based on protocol-specific criteria.

Infigratinib tablets to be administered by mouth.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation
Timepoint [1] 0 0
Up to 18 months
Primary outcome [2] 0 0
Change from baseline in annualized height velocity
Timepoint [2] 0 0
Up to 18 months
Primary outcome [3] 0 0
PK parameters of infigratinib (Cmax- PK substudy only)
Timepoint [3] 0 0
21 days
Primary outcome [4] 0 0
PK parameters of infigratinib (Clast- PK substudy only)
Timepoint [4] 0 0
21 days
Primary outcome [5] 0 0
PK parameters of infigratinib (Tmax- PK substudy only)
Timepoint [5] 0 0
21 days
Primary outcome [6] 0 0
PK parameters of infigratinib (AUC24- PK substudy only)
Timepoint [6] 0 0
21 days
Primary outcome [7] 0 0
PK parameters of infigratinib (T1/2- PK substudy only)
Timepoint [7] 0 0
21 days
Primary outcome [8] 0 0
PK parameters of infigratinib (AUCinf- PK substudy only)
Timepoint [8] 0 0
21 days
Primary outcome [9] 0 0
PK parameters of infigratinib (CL/F- PK substudy only)
Timepoint [9] 0 0
21 days
Primary outcome [10] 0 0
PK parameters of infigratinib (Vz/F- PK substudy only)
Timepoint [10] 0 0
21 days
Primary outcome [11] 0 0
PK parameters of infigratinib (Racc- PK substudy only)
Timepoint [11] 0 0
21 days
Secondary outcome [1] 0 0
Incidence of adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability
Timepoint [1] 0 0
Up to 18 months
Secondary outcome [2] 0 0
Absolute height velocity (annualized to cm/year), expressed numerically and as Z-score in relation to ACH and non-ACH tables
Timepoint [2] 0 0
Up to 18 months
Secondary outcome [3] 0 0
Absolute and change from baseline in weight (kg)
Timepoint [3] 0 0
Up to 18 months
Secondary outcome [4] 0 0
Absolute and change from baseline in sitting height (cm)
Timepoint [4] 0 0
Up to 18 months
Secondary outcome [5] 0 0
Absolute and change from baseline in head circumference (cm)
Timepoint [5] 0 0
Up to 18 months
Secondary outcome [6] 0 0
Absolute and change from baseline in upper and lower arm length (cm)
Timepoint [6] 0 0
Up to 18 months
Secondary outcome [7] 0 0
Absolute and change from baseline in thigh length (cm)
Timepoint [7] 0 0
Up to 18 months
Secondary outcome [8] 0 0
Absolute and change from baseline in knee height (cm)
Timepoint [8] 0 0
Up to 18 months
Secondary outcome [9] 0 0
Absolute and change from baseline in arm span (cm)
Timepoint [9] 0 0
Up to 18 months
Secondary outcome [10] 0 0
Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)
Timepoint [10] 0 0
Up to 18 months
Secondary outcome [11] 0 0
Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)
Timepoint [11] 0 0
Up to 18 months
Secondary outcome [12] 0 0
Changes in pharmacodynamic parameters by assessing collagen X marker
Timepoint [12] 0 0
Up to 18 months

Eligibility
Key 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.
Minimum age
3 Years
Maximum age
11 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
84
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Murdoch Children's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Delaware
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
France
State/province [7] 0 0
Lyon
Country [8] 0 0
France
State/province [8] 0 0
Paris
Country [9] 0 0
France
State/province [9] 0 0
Toulouse
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid
Country [11] 0 0
Spain
State/province [11] 0 0
Málaga
Country [12] 0 0
Spain
State/province [12] 0 0
Álava
Country [13] 0 0
United Kingdom
State/province [13] 0 0
England
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Birmingham
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Bristol
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Glasgow
Country [17] 0 0
United Kingdom
State/province [17] 0 0
London
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
QED Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
QED Therapeutics VP, Clinical Development
Address 0 0
QED Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
QED Therapeutics VP, Clinical Development
Address 0 0
Country 0 0
Phone 0 0
1-877-280-5655
Fax 0 0
Email 0 0
PROPELstudyinfo@QEDTX.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04265651