A study to investigate the safety and efficacy of infigratinib compared with placebo in infants and young 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] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

27 Jan 2026 → ongoing

Decision date (initial)

2025-12-11

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, Dose response, Safety

SAD: To identify the dose of infigratinib to be used in the Phase 2 portion of the study, based on safety and exposure of single ascending doses of infigratinib.
PH2: To confirm the doses to be used in each age cohort based on safety and PK. Ph2b: To evaluate the safety and efficacy of infigratinib in infant and young children <3 years old with ACH.
Extension: To evaluate the safety and efficacy of infigratinib in participants who completed the Phase 2 or Phase 2b portion of the study until they have reached 3 years old (+6 months)

Secondary objectives 7

1. Ph2: To evaluate the safety of oral daily doses of infigratinib.
2. Ph2: To evaluate changes in indicators of growth and body proportions.
3. Ph2: To evaluate the potential effect on infigratinib in ACH related complications.
4. Ph2b: To evaluate changes in other in key indicators of growth and body proportions.
5. Ph2b: To evaluate the pharmacokinetic (PK) profile of infigratinib and its active metabolites in participants with ACH after administration of oral infigratinib.
6. Ph2b: To evaluate changes in ACH related complications.
7. Extension: To evaluate the potential effect on infigratinib in ACH related complications.

Conditions and MedDRA coding

Achondroplasia

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000022-PIP34-98

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Diagnosis of ACH confirmed by genetic testing. If prospective participants had prior genetic testing, the diagnosis must be confirmed by a report from a certified laboratory, documenting the specific mutation.
2. Age 0 to 32 months (2 years and 8 months) at screening.
3. Signed informed consent, which must be obtained from each participant’s parent(s) or legal guardian.
4. Parent(s)/Guardian(s) willing and able to attend all study visits and comply with all study requirements.
5. Parent(s)/Guardian(s) willing and able to comply with the routine care of the study participants according to local guidance for the management of infants and young children with ACH.
6. In breastfeeding infants/young children, the mother must be willing and able to discontinue treatment with a drug that can be harmful to the participant, as this could confound the assessment of safety (ie, risk of developing an ADR to medication exposure via breast milk) or could impact the PK of infigratinib (a noncomprehensive list of prohibited medications is included in Appendix 7 [Section 10.6]). If discontinuation of treatment is not possible, the mother must be willing and able to stop the nursing of the participant.
7. Able to swallow age-appropriate oral medication.
8. In participants <1 year old, be compliant with recommended vitamin D supplementation of 5-10 μg/day or higher (or as recommended by country specific guidelines).

Exclusion criteria 9

1. Gastroesophageal reflux disease requiring prolonged treatment (>1 week) with prohibited medications.
2. History of fracture of a long bone or spine within 6 months prior to screening.
3. Any other significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib and/or would require treatment with a prohibited medication, and/or would place the participant at high risk for poor treatment compliance or for failure to complete the study.
4. Gestational age at birth <37 weeks and/or birth weight <2500 grams.
5. Regular long-term (>3 weeks; more than twice/year) treatment 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. NOTE: Low-dose topical, inhaled, or intranasal corticosteroids are acceptable.
6. Current evidence of endocrine alterations of calcium/phosphorus homeostasis, including serum calcium and/or phosphorus outside of the normal range for age at screening.
7. Allergy or hypersensitivity to any components of the study drug.
8. History or presence of ectopic tissue X (based on participant medical history).
9. History or presence of malignancy (based on participant medical history).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. SAD: Safety.
2. SAD: PK of infigratinib and its active metabolites.
3. Ph2: Safety: TEAEs that lead to dose decrease or discontinuation.
4. PH2: PK of infigratinib and its active metabolites.
5. Ph2b: AEs, SAEs, including clinically significant changes in: vital signs, laboratory assessments, physical examination (including fontanelles closure when applicable), ECG, imaging (including bone abnormalities not common in ACH), laboratory test results (including hyperphosphatemia), ocular events, abnormalities in teeth formation and eruption; delays in developmental milestones based on milestone charts for ACH (Ireland 2010).
6. Ph2b: Change from BL to Week 52 in body length Z-score in relation to ACH tables. - BL corresponds to the body length Z-score at Day 1.
7. Extension: AEs, SAEs, including clinically significant changes in: vital signs, physical examination (including fontanelles closure when applicable), ECG, imaging (including bone abnormalities not common in ACH), laboratory test results (including hyperphosphatemia), ocular events, abnormalities in teeth formation and eruption; delays in developmental milestones based on milestone charts for ACH (Ireland 2010).
8. Extension: Change over time in body length Z-score in relation to ACH tables.

Secondary endpoints 29

1. Ph2: AEs, SAEs, including clinically significant changes in: vital signs, laboratory assessments, physical examination (including fontanelles closure when applicable), ECG, imaging (including bone abnormalities not common in ACH), laboratory test results (including hyperphosphatemia), ocular events, abnormalities in teeth formation and eruption; delays in developmental milestones based on milestone charts for ACH (Ireland 2010).
2. Ph2: Mean and change from BL in body length Z-score at Week 52 (in relation to ACH tables; BL: values at Day 1).
3. Ph2: Mean and change from BL to Week 52 in upper- to lower-body segment ratio.
4. Ph2: Mean and change from BL to Week 52 in head circumference/body length ratio.
5. Ph2: Health-related quality of life using Infant Toddler Quality of Life (ITQoL).
6. Ph2: Milestone development, including social/emotional, language/communication; cognitive; movement/physical development and specific movement strategies used by children with ACH (Ireland 2010).
7. Ph2: Skull and brain morphology using magnetic resonance imaging (MRI).
8. Ph2: Age at closure of cranial sutures and fontanelles.
9. Ph2: Incidence of surgical interventions, including cervical decompression, adenotonsillectomy, and tympanostomy.
10. Ph2: Incidence and severity of sleep apnea.
11. Ph2: Bone morphology as assessed by bilateral x-rays of lower extremity and whole spine.
12. Ph2b: Body length Z-score at Week 52 in relation to ACH tables.
13. Ph2b: Mean and change from BL to Week 52 in upper-to lower-body segment ratio.
14. Ph2b: Mean and change from BL in head circumference/body length ratio.
15. Ph2b: PK of infigratinib and its active metabolites.
16. Ph2b: Health-related quality of life using ITQoL.
17. Ph2b: Milestone development, including social/emotional, language/communication; cognitive; movement/physical development and specific movement strategies used by children with ACH (Ireland 2010).
18. Ph2b: Skull and brain morphology using MRI.
19. Ph2b: Age at closure of cranial sutures and fontanelles.
20. Ph2b: Incidence of surgical interventions, including but not limited to adenotonsillectomy, and tympanostomy.
21. Ph2b: Incidence and severity of sleep apnea.
22. Ph2b: Bone morphology as assessed by bilateral x-rays of lower extremities and whole spine.
23. Extension: Change over time in upper- to lower-body segment ratio.
24. Extension: Change over time in head circumference/body length ratio.
25. Extension: Health-related quality of life using ITQoL.
26. Extension: Milestone development, including social/emotional, language/communication; cognitive; movement/physical development and specific movement strategies used by children with ACH (Ireland 2010).
27. Extension: Age at closure of cranial sutures and fontanelles.
28. Extension: Incidence of surgical interventions, including cervical decompression, adenotonsillectomy, and tympanostomy.
29. Extension: Bone morphology as assessed by bilateral x-rays of lower extremity and whole spine.

Investigational products

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

Test 3

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 Clinical Development

Public contact point

Organisation

Qed Therapeutics Inc.

Contact name

Regulatory Affairs

Third parties 10

Locations

2 EU/EEA countries · 2 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 22 files

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

Application history

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