A Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Infigratinib in Children with Achondroplasia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

QED Therapeutics Inc., Qed Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Genetic Phenomena [G05], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

20 Aug 2024 → 18 Dec 2025

Decision date (initial)

2024-03-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

QED Therapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Therapy

To evaluate the efficacy of infigratinib in pediatric subjects with ACH 3 to <18 years of age who have potential to grow.

Secondary objectives 9

1. To evaluate changes in other key indicators of growth and body proportions.
2. To evaluate changes in other parameters of growth and body proportions.
3. To evaluate the safety and tolerability of infigratinib in children with ACH.
4. To evaluate the efficacy of infigratinib in children with ACH who are ≥5 years of age.
5. To evaluate the impact of the changes of growth and body proportions on the physical functioning of children
6. To evaluate changes in cognitive functions.
7. To evaluate the PK profile of infigratinib and its active metabolites in children with ACH after administration of oral infigratinib.
8. To evaluate PD indicators of bone growth.
9. To evaluate the acceptability and palatability of infigratinib.

Conditions and MedDRA coding

Achondroplasia

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002594-PIP02-20

Plan to share IPD

No

IPD plan description

no for now

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subject must be 3 to <18 years of age at screening with growth potential defined as AHV of >1.5 cm/year over a period of at least 6 months of participation in the PROPEL observational study (QGBJ398-001), pubertal Tanner stage ≤4, and bone age ≤13 years in females and ≤15 years in males.
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.
7. Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche
8. If sexually active, all subjects must be willing to use a highly effective method of contraception while taking study drug and for 1 month after the last dose of study drug.
9. Signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF 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)
10. Subjects for whom the licensed treatment option (vosoritide) is contraindicated based on investigator judgement or is unavailable/inaccessible, or not a viable option (eg, subject or family unwilling or unable to administer a daily injectable medication).

Exclusion criteria 11

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.
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 for over 3 weeks within 6 months of the screening visit.
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 CYP3A or prolonged treatment (>1 week) with medications that alter the pH of the gastrointestinal tract.
11. Subjects receiving medications which could increase serum phosphorus and/or calcium concentration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline (BL) in AHV, compared to placebo [Time Frame: Week 52]

Secondary endpoints 20

1. Change from BL in height Z-score (in relation to ACH tables), compared to placebo [Time Frame: Week 52]
2. Change from BL in upper to lower body segment ratio, compared to placebo [Time Frame: Week 52]
3. Change from BL in height Z-score (in relation to non-ACH tables), compared to placebo [Time Frame: Week 52]
4. AVH compared to placebo [Time Frame: Week 52]
5. Absolute and change from baseline in upper arm to forearm length ratio (cm), compared to placebo [Time Frame: Week 52]
6. Absolute and change from baseline in upper leg to lower leg length ratio (cm), compared to placebo [Time Frame: Week 52]
7. Absolute and change from baseline in arm span (cm) to standing height ratio, compared to placebo [Time Frame: Week 52]
8. Absolute and change from baseline in head circumference (cm) to standing height ratio, compared to placebo [Time Frame: Week 52]
9. Absolute value and change in body mass index, compared to placebo [Time Frame: Week 52]
10. Incidence of adverse events [Time Frame: Week 52]
11. Change from BL in AHV in children ≥5 years of age, compared to placebo [Time Frame: Week 52]
12. Change from BL in the Physical Functioning Scale of the PedsQL child report compared to placebo [Time Frame: Week 52]
13. Change in psychomotor function assessed by age-appropriate computerized tests (Detection Test), compared to placebo [Time Frame: Week 52]
14. Change from BL in attention assessed by age-appropriate computerized tests (Identification Test) [Time Frame: Week 52]
15. Change from BL in visual learning assessed by age-appropriate computerized tests (One Card Learning Test) [Time Frame: Week 52]
16. Change from BL in working memory assessed by age-appropriate computerized tests (One Back Test) [Time Frame: Week 52]
17. Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax) [Time Frame: Week 52]
18. Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax) [Time Frame: Week 52]
19. Change from BL in pharmacodynamic parameters by assessing collagen X marker, compared to placebo [Time Frame: Week 52]
20. Evaluate the acceptability and palatability of infigratinib using a 5-point hedonic scale [Time Frame: Week 13]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

QED Therapeutics Inc.

Sponsor organisation

QED Therapeutics Inc.

Address

75 Federal Street

City

San Francisco

Postcode

94107-1414

Country

United States

Scientific contact point

Organisation

QED Therapeutics Inc.

Contact name

Senior Medical Director

Public contact point

Organisation

QED Therapeutics Inc.

Contact name

VP Regulatory Affairs

Qed Therapeutics Inc.

Sponsor organisation

Qed Therapeutics Inc.

Address

1800 Owens Street Ste C1200

City

San Francisco

Postcode

94158-2584

Country

United States

Scientific contact point

Organisation

Qed Therapeutics Inc.

Contact name

Senior Medical Director

Public contact point

Organisation

Qed Therapeutics Inc.

Contact name

VP Regulatory Affairs

Third parties 16

Locations

5 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 172 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications