A study to evaluate long-term Infigratinib in children with Achondroplasia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Qed Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

8 Feb 2022 → ongoing

Decision date (initial)

2024-09-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

QED Therapeutics, Inc.

External identifiers

EU CT number

2024-513857-55-00

EudraCT number

2021-001855-15

ClinicalTrials.gov

NCT05145010

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Efficacy, Safety

1. To evaluate the safety and tolerability of long-term administration of daily doses of oral infigratinib in subjects with ACH.
2. To evaluate the efficacy of long-term administration of daily doses of oral infigratinib in subjects with ACH as assessed as changes over time in standing height Z-score.

Secondary objectives 4

1. To evaluate changes in other indicators of growth and development in subjects with ACH receiving long-term treatment with oral infigratinib, such as: ○ Change over time in height velocity (HV) Z-score in relation to ACH and nonACH growth charts. ○ Changes over time in other anthropometric parameters after administration of oral infigratinib. ○ Age at puberty onset and progression of pubertal development.
2. To evaluate changes over time in ACH disease burden with long-term administration of oral doses of infigratinib, including disease specific complications, health-related quality of life (HRQoL), overall body pain, and functional abilities.
3. To evaluate treatment benefit as assessed by a qualitative interview of the subject and caregiver.
4. To evaluate potential changes in cognitive functions (safety evaluation).

Conditions and MedDRA coding

Achondroplasia

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Food And Drug Administration, National Agency For The Safety Of Medicine And Health Products, European Medicines Agency, Danish Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002594-PIP02-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Inclusion Criteria for Rollover Subjects 1. Pediatric subjects with ACH who have completed a previous QEDsponsored interventional study with infigratinib. 2. Subjects and parent(s), legal guardians, or caregivers are willing and able to comply with study visits and study procedures. 3. Subjects are able to swallow oral medication. 4. Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche. 5. If sexually active, subject 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. 6. The PI, or a person designated by the PI, will obtain written informed consent from each subject's parents(s), legal guardian(s), or caregiver(s) and the subject's assent, when applicable, before any study-specific activity is performed.
2. Inclusion Criteria for Treatment Naïve Subjects 1. Subject must be 3 to <18 years of age at screening and have growth potential 2. Subjects and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures. 3. Subjects are able to swallow oral medication. 4. Subjects who have a diagnosis of ACH, documented clinically and confirmed by genetic testing. 5. Subjects have at least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398-001) before study entry. 6. Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche. 7. If sexually active, subject 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. 8. The PI, or a person designated by the PI, will obtain written informed consent from each subject's parent(s), legal guardian(s), or caregiver(s) and the subject's assent, when applicable, before any study-specific activity is performed.

Exclusion criteria 2

1. Exclusion Criteria for Rollover Subjects 1. Subject has concurrent circumstance, disease, or condition that, in the view of the PI and/or sponsor, would interfere with study participation or safety evaluations. 2. Subjects who developed a medical condition that will require the initiation of treatment with a prohibited medication. 3. Subjects that prematurely discontinued a prior QED-sponsored interventional study with infigratinib. 4. Current participation in an ongoing clinical study with a sponsor other than QED. 5. Subjects that have reached final height or near final height
2. Exclusion Criteria for Treatment Naïve Subjects 1. Subjects who have hypochondroplasia or short stature condition other than ACH (eg, trisomy 21, pseudoachondroplasia, psychosocial short stature). 2. Subjects who have significant concurrent disease or condition that, in the view of the PI and/or sponsor, would represent an increased risk to the subject or would interfere with study participation or safety evaluations 3. Subjects who have a history of malignancy. 4. Subjects who are currently receiving treatment with agents that are known strong inducers or inhibitors of cytochrome P450 (CYP) 3A4 5. Subjects who discontinued treatment with prohibited medications for at least 5 half-lives before screening are eligible. 6. Subjects who have received treatment with growth hormone, insulinlike growth factor 1 (IGF 1), anabolic steroids or any investigational or approved drug for the treatment of ACH in the previous 6 months. 7. Subjects who have significant abnormality in screening laboratory results. 8. Subjects who have had a fracture within 12 months of screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of treatment emergent adverse events (TEAE) and serious TEAE
2. Changes over time in height Z-score in relation to ACH and non-ACH growth charts.

Secondary endpoints 17

1. Change over time in absolute height velocity, expressed as height velocity Z-score in relation to ACH and non-ACH growth charts.
2. Changes over time in body proportions
3. Changes over time in weight Z-score
4. Changes over time in BMI
5. Age of puberty onset and time to Tanner stage ≥4.
6. Changes over time in number of episodes of otitis media per year.
7. Changes over time in number of episodes and/or severity of sleep apnea.
8. Changes over time in range of motion (elbow).
9. Changes over time in skeletal abnormalities of the lower extremities and spine
10. Changes in health-related quality of life (HRQoL) as assessed by Pediatric Quality of Life Inventory (PedsQL)
11. Changes in health-related quality of life (HRQoL) as assessed by Quality of Life in Short Stature Youth questionnaire (QoLISSY)
12. Overall pain as assessed by Numeric Rating Scale for pain (Pain-NRS)
13. Changes in functional abilities as evaluated by Functional Independence Measure for Children (WeeFIM)
14. Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Severity (PGI-S)
15. Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Change (PGI-C)
16. Subject and caregiver evaluation of treatment benefit as assessed by a qualitative interview
17. Changes in cognitive functions assessed by age-appropriate computerized tests

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

QED Therapeutics VP Regulatory

Public contact point

Organisation

Qed Therapeutics Inc.

Contact name

QED Therapeutics VP Regulatory

Third parties 18

Locations

4 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 165 files

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

Application history

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