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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06164951




Registration number
NCT06164951
Ethics application status
Date submitted
29/11/2023
Date registered
11/12/2023

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Infigratinib in Children and Adolescents with Achondroplasia
Scientific title
A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Infigratinib in Children 3 to <18 Years of Age with Achondroplasia: PROPEL 3
Secondary ID [1] 0 0
QBGJ398-303
Universal Trial Number (UTN)
Trial acronym
PROPEL3
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 0.25 mg/kg/day
Treatment: Drugs - Placebo Comparator 0.25 mg/kg/day

Experimental: Infigratinib 0.25 mg/kg/day - Infigratinib at 2, 3.5, 5, 7, 10 mg

Placebo comparator: Placebo 0.25 mg/kg/day - Placebo Comparator at 2, 3.5, 5, 7, 10 mg


Treatment: Drugs: Infigratinib 0.25 mg/kg/day
Daily doses of oral Infigratinib (sprinkle capsules) at 2, 3.5, 5, 7, 10 mg

Treatment: Drugs: Placebo Comparator 0.25 mg/kg/day
Daily doses of oral Placebo Comparator (sprinkle capsules) at 2, 3.5, 5, 7, 10 mg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline (BL) in annualized height velocity (cm/year)
Timepoint [1] 0 0
Week 52
Secondary outcome [1] 0 0
Change from BL in height Z-score (in relation to ACH tables)
Timepoint [1] 0 0
Week 52
Secondary outcome [2] 0 0
Change from BL in upper to lower body segment ratio
Timepoint [2] 0 0
Week 52
Secondary outcome [3] 0 0
Change from BL in height Z-score (in relation to non-ACH tables)
Timepoint [3] 0 0
Week 52
Secondary outcome [4] 0 0
Annualized height velocity (cm/year)
Timepoint [4] 0 0
Week 52
Secondary outcome [5] 0 0
Absolute and change from baseline in upper arm to forearm length ratio (cm)
Timepoint [5] 0 0
Week 52
Secondary outcome [6] 0 0
Absolute and change from baseline in upper leg to lower leg length ratio (cm)
Timepoint [6] 0 0
Week 52
Secondary outcome [7] 0 0
Absolute and change from baseline in arm span (cm) to standing height ratio
Timepoint [7] 0 0
Week 52
Secondary outcome [8] 0 0
Absolute and change from baseline in head circumference (cm) to standing height ratio
Timepoint [8] 0 0
Week 52
Secondary outcome [9] 0 0
Absolute value and change in body mass index
Timepoint [9] 0 0
Week 52
Secondary outcome [10] 0 0
Incidence of adverse events
Timepoint [10] 0 0
Week 52
Secondary outcome [11] 0 0
Change from BL in annualized height velocity (cm/year) in children 5 years old and older, compared to placebo
Timepoint [11] 0 0
Week 52
Secondary outcome [12] 0 0
Change from BL in the Physical Functioning dimension of the Pediatric Quality of Life Generic Core Scale Short Form
Timepoint [12] 0 0
Week 52
Secondary outcome [13] 0 0
Change in psychomotor function assessed by age-appropriate computerized tests (Detection Test), compared to placebo
Timepoint [13] 0 0
Week 52
Secondary outcome [14] 0 0
Change from BL in attention assessed by age-appropriate computerized tests (Identification Test)
Timepoint [14] 0 0
Week 52
Secondary outcome [15] 0 0
Change from BL in visual learning assessed by age-appropriate computerized tests (One Card Learning Test)
Timepoint [15] 0 0
Week 52
Secondary outcome [16] 0 0
Change from BL in working memory assessed by age-appropriate computerized tests (One Back Test)
Timepoint [16] 0 0
Week 52
Secondary outcome [17] 0 0
Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)
Timepoint [17] 0 0
Week 52
Secondary outcome [18] 0 0
Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)
Timepoint [18] 0 0
Week 52
Secondary outcome [19] 0 0
Change from BL in collagen X marker concentration (ug/L)
Timepoint [19] 0 0
Week 52
Secondary outcome [20] 0 0
Evaluate the acceptability and palatability of infigratinib using a 5-point hedonic scale
Timepoint [20] 0 0
Week 13

Eligibility
Key inclusion criteria
1. 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
2. Subjects who have a diagnosis of ACH that has been documented clinically and confirmed by genetic testing.
3. Subjects must have completed at least 26 weeks in the PROPEL (QBGJ398-001) study before screening.
4. Subjects are able to swallow oral medication.
5. Subjects and parent(s), legal guardian(s), or caregivers are willing and able to comply with study visits and study procedures.
6. Subjects are ambulatory and able to stand without assistance.

Sex and Contraceptive/Barrier Requirements
7. Negative pregnancy test in girls =10 years of age or girls of any age who have experienced menarche.
8. 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
9. 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)
Minimum age
3 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medical Conditions

1. Subjects who have hypochondroplasia or short stature condition other than ACH.
2. Significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib.
3. Current evidence of clinically significant corneal or retinal disorder/keratopathy -confirmed by ophthalmic examination.
4. 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.
5. History and/or current evidence of extensive ectopic tissue calcification.
6. History of malignancy.

Prior/Concomitant Therapy
7. Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH or short stature.
8. 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).
9. 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.
10. 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).
11. Current evidence of endocrine alterations of calcium/phosphorus homeostasis.

Diagnostic assessments
12. Subjects who have significant abnormality in screening laboratory results.

Other Exclusions
13. Having had a fracture of the long bones (ie, extremities) or spine within 12 months prior to screening.
14. Pregnant or breastfeeding at the screening visit or planning to become pregnant (self or partner) at any time during the study.
15. Allergy or hypersensitivity to any components of the study drug.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2026
Actual
Sample size
Target
110
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
QED Investigative Site - 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
Colorado
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
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Wisconsin
Country [8] 0 0
Argentina
State/province [8] 0 0
Capital Federal
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
France
State/province [12] 0 0
Bron
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
France
State/province [14] 0 0
Toulouse
Country [15] 0 0
Italy
State/province [15] 0 0
Rome
Country [16] 0 0
Norway
State/province [16] 0 0
Bergen
Country [17] 0 0
Norway
State/province [17] 0 0
Oslo
Country [18] 0 0
Singapore
State/province [18] 0 0
Singapore
Country [19] 0 0
Spain
State/province [19] 0 0
Málaga
Country [20] 0 0
Spain
State/province [20] 0 0
Vitoria-Gasteiz
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Birmingham
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Bristol
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Glasgow
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Manchester
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Sheffield

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, Inc. Medical Director, 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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
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/NCT06164951