An Interventional Study of Infigratinib in Children With Hypochondroplasia

Официальное название

A Phase 2/3, Multicenter, Open-Label Phase Followed by a Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Infigratinib in Children With Hypochondroplasia: ACCEL 2/3

Обзор

ACCEL2/3 is a Phase 2/3 study. The purpose of the Phase 2 portion of the study (ACCEL2/3) is to evaluate the efficacy and safety of infigratinib in children with hypochondroplasia (HCH) receiving infigratinib at one of two doses, who have completed at least 26 weeks of participation in QED-sponsored ACCEL (QBGJ398-004).

Подробное описание

ACCEL 2/3 is a Phase 2/3 study that comprises of 2 portions. The Phase 2 portion is an open-label, portion in children with HCH aged 5 to 11 years old followed by a Phase 3 portion which is double-blind, placebo-controlled in children with HCH aged \>3 years old to \<18 years old.

Вмешательства

• Препарат infigratinib 0.128 mg/kg/day
  Oral infigratinib 0.128 mg/kg/day
• Препарат infigratinib 0.25 mg/kg/day
  Oral infigratinib 0.25 mg/kg/day

Первичные конечные точки

• Change from baseline (BL) in Annualized Height Velocity (AHV; cm/year) [Срок оценки: 26 weeks]
• Incidence, severity, and seriousness of adverse events (AEs) that require dose reduction or discontinuation [Срок оценки: at least 26 weeks]

Вторичные конечные точки (6)

• Change from BL in height Z-score (in relation to both HCH and average height tables) [Срок оценки: 52 weeks]
• Change from BL in upper to lower body segment ratio (cm) [Срок оценки: 52 weeks]
• Changes in cognitive function (as assessed by age appropriate computerized tests) [Срок оценки: 52 weeks]
• Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax) [Срок оценки: 52 weeks]
• Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax) [Срок оценки: 52 weeks]
• Change from BL in collagen X marker (CXM) levels [Срок оценки: 52 weeks]

Критерии участия

Критерии включения

• Participants must have completed at least 26 weeks and still be on the observational study (QBGJ398-004).
• Phase 2 portion: Participants 5-11 years of age (inclusive).
• Phase 3 portion: Participants 3 to <18 years of age at screening with growth potential
• Diagnosis of HCH documented clinically by the presence of disproportionate short stature and confirmed with a molecular test.
• Participants are able to swallow oral medication.
• Participants and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures.
• Participants are ambulatory and able to stand without assistance. Sex and Contraceptive/Barrier Requirements
• Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
• If sexually active, participants whether male or female, must be willing to use a highly effective method of contraception, as relevant, while taking study drug and for 1 month after the last dose of study drug.
• Signed informed consent.

Критерии исключения

• Participants who have ACH or a short stature condition other than HCH.
• Significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib.
• Current evidence of clinically significant corneal or retinal disorder/keratopathy confirmed by ophthalmic examination.
• Concurrent circumstance, disease, or condition that, in the view of the investigator and/or sponsor, would interfere with study participation or safety evaluations.
• History and/or current evidence of extensive ectopic tissue calcification.
• History of malignancy.
• Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH, HCH, or short stature.
• Regular long-term treatment (≥3 weeks) with supraphysiologic doses of glucocorticoid.
• Previous limb-lengthening surgery at any time or planned/expected to have limb-lengthening or guided growth surgery while participating in the study.
• Participants receiving medications which could increase serum phosphorus and/or calcium concentrations
• Clinically significant abnormality in any laboratory test result at screening.
• Pregnant or breastfeeding at the screening visit or planning to become pregnant (self or partner) at any time during the study.
• Allergy to any components of the study drug.
• Concurrent circumstance, disease, or condition that would interfere with study participation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• UCSF Benioff Children's Hospital — Oakland
• Childrens Hospital Colorado — Aurora
• Children's National Hospital — Washington D.C.
• Johns Hopkins School of Medicine — Baltimore
• University of Missouri — Columbia
• Cincinnati Children's Hospital Medical Center — Cincinnati
• Vanderbilt University Medical Center — Nashville
• University of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic — Madison

Канада · 3 центра

• London Health Services Centre - Children's Hospital of Western Ontario — London
• Children's Hospital of Eastern Ontario Research Institute — Ottawa
• Université de Montréal - Centre Hospitalier Universitaire Sainte-Justine — Montreal

Франция · 3 центра

• Hôpital Femme Mère Enfant — Bron
• Hôpital Universitaire Necker-Enfants Malades — Paris
• Centre Hospitalier Universitaire (CHU) de Toulouse - Hôpital des Enfants — Toulouse

Великобритания · 3 центра

• Manchester University — Manchester
• Sheffield Children's Hospital — Sheffield
• Glasgow Clinical Research Facility, Queen Elizabeth University Hospital — Glasgow

Норвегия · 2 центра

• Haukeland University Hospital — Bergen
• Paediatric Clinical Research Unit at Oslo University Hospital — Oslo

Австралия · 1 центр

• Murdoch Children's Research Institute - The Royal Children's Hospital Melbourne — Parkville

Португалия · 1 центр

• Hospital Pediátrico de Coimbra — Coimbra

Сингапур · 1 центр

• KK Women's and Children's Hospital — Singapore

Испания · 1 центр

• Unidad de Cirugía Artroscopica, Hopsital MIKS — Vitoria-Gasteiz

Швеция · 1 центр

• Astrid Lindgren Children's Hospital — Solna

Идентификаторы

NCT: NCT06873035 · QBGJ398-304

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗