INFIGRATINIB for Achondroplasia

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Age 0 to 32 months (2 years and 8 months) at screening."}
• {"criterion_text":"- Signed informed consent, which must be obtained from each participant’s parent(s) or legal guardian."}
• {"criterion_text":"- Parent(s)/Guardian(s) willing and able to attend all study visits and comply with all study requirements."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Able to swallow age-appropriate oral medication."}
• {"criterion_text":"- 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

• {"criterion_text":"- Gastroesophageal reflux disease requiring prolonged treatment (>1 week) with prohibited medications."}
• {"criterion_text":"- History of fracture of a long bone or spine within 6 months prior to screening."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Gestational age at birth <37 weeks and/or birth weight <2500 grams."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Current evidence of endocrine alterations of calcium/phosphorus homeostasis, including serum calcium and/or phosphorus outside of the normal range for age at screening."}
• {"criterion_text":"- Allergy or hypersensitivity to any components of the study drug."}
• {"criterion_text":"- History or presence of ectopic tissue X (based on participant medical history)."}
• {"criterion_text":"- History or presence of malignancy (based on participant medical history)."}

Primary endpoints

• {"endpoint_text":"- SAD: Safety.","definition_or_measurement_approach":""}
• {"endpoint_text":"- SAD: PK of infigratinib and its active metabolites.","definition_or_measurement_approach":"Pharmacokinetic assessment of infigratinib and active metabolites (PK sampling)."}
• {"endpoint_text":"- Ph2: Safety: TEAEs that lead to dose decrease or discontinuation.","definition_or_measurement_approach":"Assessment of treatment-emergent adverse events (TEAEs) causing dose reduction or discontinuation."}
• {"endpoint_text":"- PH2: PK of infigratinib and its active metabolites.","definition_or_measurement_approach":"Pharmacokinetic assessment of infigratinib and active metabolites (PK sampling)."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Safety evaluations including AE/SAE reporting, vital signs, lab tests (including phosphate), ECG, imaging, ocular assessments, dental assessments, and developmental milestone assessments per Ireland 2010 charts."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Change in body length Z-score from baseline (Day 1) to Week 52 using ACH reference tables."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Ongoing safety monitoring in extension similar to Ph2b: AE/SAE reporting and clinical/laboratory/imaging assessments as specified."}
• {"endpoint_text":"- Extension: Change over time in body length Z-score in relation to ACH tables.","definition_or_measurement_approach":"Longitudinal change in body length Z-score relative to ACH tables during the extension period."}

Secondary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Safety assessments as described (AE/SAE reporting, clinical and laboratory monitoring, imaging, developmental milestones per Ireland 2010)."}
• {"endpoint_text":"- Ph2: Mean and change from BL in body length Z-score at Week 52 (in relation to ACH tables; BL: values at Day 1).","definition_or_measurement_approach":"Mean and change from baseline body length Z-score at Week 52 using ACH tables."}
• {"endpoint_text":"- Ph2: Mean and change from BL to Week 52 in upper- to lower-body segment ratio.","definition_or_measurement_approach":"Anthropometric assessment of upper-to-lower body segment ratio change from baseline to Week 52."}
• {"endpoint_text":"- Ph2: Mean and change from BL to Week 52 in head circumference/body length ratio.","definition_or_measurement_approach":"Assessment of head circumference to body length ratio change from baseline to Week 52."}
• {"endpoint_text":"- Ph2: Health-related quality of life using Infant Toddler Quality of Life (ITQoL).","definition_or_measurement_approach":"Patient/parent-reported ITQoL questionnaire."}
• {"endpoint_text":"- Ph2: Milestone development, including social/emotional, language/communication; cognitive; movement/physical development and specific movement strategies used by children with ACH (Ireland 2010).","definition_or_measurement_approach":"Developmental milestone assessments per Ireland 2010 across multiple domains."}
• {"endpoint_text":"- Ph2: Skull and brain morphology using magnetic resonance imaging (MRI).","definition_or_measurement_approach":"MRI assessment of skull and brain morphology."}
• {"endpoint_text":"- Ph2: Age at closure of cranial sutures and fontanelles.","definition_or_measurement_approach":"Clinical assessment of cranial suture and fontanelle closure timing."}
• {"endpoint_text":"- Ph2: Incidence of surgical interventions, including cervical decompression, adenotonsillectomy, and tympanostomy.","definition_or_measurement_approach":"Recording incidence of specified surgical procedures."}
• {"endpoint_text":"- Ph2: Incidence and severity of sleep apnea.","definition_or_measurement_approach":"Assessment and reporting of sleep apnea incidence and severity (clinical/sleep study where applicable)."}
• {"endpoint_text":"- Ph2: Bone morphology as assessed by bilateral x-rays of lower extremity and whole spine.","definition_or_measurement_approach":"Radiographic assessment (bilateral x-rays) of lower extremities and whole spine."}
• {"endpoint_text":"- Ph2b: Body length Z-score at Week 52 in relation to ACH tables.","definition_or_measurement_approach":"Body length Z-score at Week 52 using ACH reference tables."}
• {"endpoint_text":"- Ph2b: Mean and change from BL to Week 52 in upper-to lower-body segment ratio.","definition_or_measurement_approach":"Anthropometric assessment of upper-to-lower body segment ratio change from baseline to Week 52."}
• {"endpoint_text":"- Ph2b: Mean and change from BL in head circumference/body length ratio.","definition_or_measurement_approach":"Assessment of head circumference to body length ratio change from baseline to Week 52."}
• {"endpoint_text":"- Ph2b: PK of infigratinib and its active metabolites.","definition_or_measurement_approach":"Pharmacokinetic sampling and analysis of infigratinib and active metabolites."}
• {"endpoint_text":"- Ph2b: Health-related quality of life using ITQoL.","definition_or_measurement_approach":"ITQoL questionnaire assessment."}
• {"endpoint_text":"- Ph2b: Milestone development, including social/emotional, language/communication; cognitive; movement/physical development and specific movement strategies used by children with ACH (Ireland 2010).","definition_or_measurement_approach":"Developmental milestone assessments per Ireland 2010."}
• {"endpoint_text":"- Ph2b: Skull and brain morphology using MRI.","definition_or_measurement_approach":"MRI assessment of skull and brain morphology."}
• {"endpoint_text":"- Ph2b: Age at closure of cranial sutures and fontanelles.","definition_or_measurement_approach":"Clinical assessment of timing of cranial suture and fontanelle closure."}
• {"endpoint_text":"- Ph2b: Incidence of surgical interventions, including but not limited to adenotonsillectomy, and tympanostomy.","definition_or_measurement_approach":"Recording incidence of specified surgical procedures."}
• {"endpoint_text":"- Ph2b: Incidence and severity of sleep apnea.","definition_or_measurement_approach":"Assessment and recording of sleep apnea incidence and severity."}
• {"endpoint_text":"- Ph2b: Bone morphology as assessed by bilateral x-rays of lower extremities and whole spine.","definition_or_measurement_approach":"Radiographic assessment (bilateral x-rays) of lower extremities and whole spine."}
• {"endpoint_text":"- Extension: Change over time in upper- to lower-body segment ratio.","definition_or_measurement_approach":"Longitudinal assessment of upper-to-lower body segment ratio during extension."}
• {"endpoint_text":"- Extension: Change over time in head circumference/body length ratio.","definition_or_measurement_approach":"Longitudinal assessment of head circumference/body length ratio during extension."}
• {"endpoint_text":"- Extension: Health-related quality of life using ITQoL.","definition_or_measurement_approach":"ITQoL questionnaire assessments during extension."}
• {"endpoint_text":"- Extension: Milestone development, including social/emotional, language/communication; cognitive; movement/physical development and specific movement strategies used by children with ACH (Ireland 2010).","definition_or_measurement_approach":"Developmental milestone assessments per Ireland 2010 during extension."}
• {"endpoint_text":"- Extension: Age at closure of cranial sutures and fontanelles.","definition_or_measurement_approach":"Clinical assessment of cranial suture/fontanelle closure during extension."}
• {"endpoint_text":"- Extension: Incidence of surgical interventions, including cervical decompression, adenotonsillectomy, and tympanostomy.","definition_or_measurement_approach":"Recording incidence of specified surgeries during extension."}
• {"endpoint_text":"- Extension: Bone morphology as assessed by bilateral x-rays of lower extremity and whole spine.","definition_or_measurement_approach":"Radiographic assessments during extension (bilateral x-rays)."}

Norway

Earliest CTIS Part Ii Submission Date

07-11-2025

Latest Decision Or Authorization Date

11-12-2025

Processing Time Days

34

Number Of Sites

1

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

07-11-2025

Latest Decision Or Authorization Date

10-12-2025

Processing Time Days

33

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Qed Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Suvoda LLC

Responsibilities

sponsorDuties codes: 3

Name

Icon Clinical Research LLC

Responsibilities

Central Imaging

Name

Premier Research International LLC

Responsibilities

Management of trial sites and multiple operational duties (sponsorDuties codes: 1,12,13,15,2,5,6,9)

Name

Medpace Belgium

Responsibilities

sponsorDuties codes: 4

Name

Syneos Health Clinique Inc.

Responsibilities

PK Analysis laboratory

Name

Bioclinica Inc.

Responsibilities

Central ECG

Third parties

• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Pharmacovigilance","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Medpace Belgium","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient and Travel reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Icon Clinical Research LLC","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"Storage of biosamples","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Premier Research International LLC","duties_or_roles":"sponsorDuties codes: 1,12,13,15 (Management of trial sites),2,5,6,9","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"PK Analysis laboratory","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central ECG","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}