A Study to Evaluate the Efficacy and Safety of Infigratinib in Children and Adolescents With Achondroplasia

Phase 3

• Conditions: Achondroplasia
• Interventions: Drug: Infigratinib 0.25 mg/kg/day; Drug: Placebo Comparator 0.25 mg/kg/day

• Registration Number: NCT06164951
• Lead Sponsor: QED Therapeutics, Inc.

Brief Summary

This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of infigratinib in children and adolescents with achondroplasia (ACH) who have completed at least 26 weeks of participation in the QED-sponsored study PROPEL (QBGJ398-001).

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-10
• Study First Submitted: 2023-11-29
• Study First Submitted QC: 2023-12-08
• Study First Posted: 2023-12-11
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-22
• Last Update Posted: 2024-11-26
• Primary Completion: 2025-12-31
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 110

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)

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Infigratinib 0.25 mg/kg/day	Infigratinib 0.25 mg/kg/day	Infigratinib at 2, 3.5, 5, 7, 10 mg
Placebo 0.25 mg/kg/day	Placebo Comparator 0.25 mg/kg/day	Placebo Comparator at 2, 3.5, 5, 7, 10 mg

Primary Outcome Measures

Name	Time	Method
Change from baseline (BL) in annualized height velocity (cm/year)	Week 52

Secondary Outcome Measures

Name	Time	Method
Change from BL in height Z-score (in relation to non-ACH tables)	Week 52
Absolute and change from baseline in arm span (cm) to standing height ratio	Week 52
Absolute and change from baseline in head circumference (cm) to standing height ratio	Week 52
Change in psychomotor function assessed by age-appropriate computerized tests (Detection Test), compared to placebo	Week 52	Lower score=better performance. Range values=2-6
Annualized height velocity (cm/year)	Week 52
Absolute and change from baseline in upper leg to lower leg length ratio (cm)	Week 52
Change from BL in the Physical Functioning dimension of the Pediatric Quality of Life Generic Core Scale Short Form	Week 52	Scale scores 0-100. Higher score=better Health-Related Quality of Life
Change from BL in height Z-score (in relation to ACH tables)	Week 52
Change from BL in upper to lower body segment ratio	Week 52
Absolute value and change in body mass index	Week 52
Incidence of adverse events	Week 52
Change from BL in attention assessed by age-appropriate computerized tests (Identification Test)	Week 52	Lower score=better performance. Range values=2-6
Absolute and change from baseline in upper arm to forearm length ratio (cm)	Week 52
Change from BL in annualized height velocity (cm/year) in children 5 years old and older, compared to placebo	Week 52
Change from BL in working memory assessed by age-appropriate computerized tests (One Back Test)	Week 52	Lower score=better performance. Range values=2-6
Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)	Week 52
Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)	Week 52
Change from BL in collagen X marker concentration (ug/L)	Week 52
Change from BL in visual learning assessed by age-appropriate computerized tests (One Card Learning Test)	Week 52	Higher score=better performance. Range values=0-1.6
Evaluate the acceptability and palatability of infigratinib using a 5-point hedonic scale	Week 13

Trial Locations

Locations (1)

QED Investigative Site; 🇬🇧 Sheffield, United Kingdom