Phase 2b, Randomized, Double-Blind, Placebo-Controlled Clinical Trial, Preceded by a Single Ascending Dose Portion and a Phase 2 Open-Label Portion, to Evaluate the Safety and Efficacy of Oral Infigratinib in Infants and Young Children with Achondroplasia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- SAD: Safety.
研究概览
简要总结
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)
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Extension Phase
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •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.
- •Age 0 to 32 months (2 years and 8 months) at screening.
- •Signed informed consent, which must be obtained from each participant’s parent(s) or legal guardian.
- •Parent(s)/Guardian(s) willing and able to attend all study visits and comply with all study requirements.
- •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.
- •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.
- •Able to swallow age-appropriate oral medication.
- •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).
排除标准
- •Gastroesophageal reflux disease requiring prolonged treatment (>1 week) with prohibited medications.
- •History of fracture of a long bone or spine within 6 months prior to screening.
- •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.
- •Gestational age at birth <37 weeks and/or birth weight <2500 grams.
- •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.
- •Current evidence of endocrine alterations of calcium/phosphorus homeostasis, including serum calcium and/or phosphorus outside of the normal range for age at screening.
- •Allergy or hypersensitivity to any components of the study drug.
- •History or presence of ectopic tissue X (based on participant medical history).
- •History or presence of malignancy (based on participant medical history).
结局指标
主要结局
SAD: Safety.
SAD: Safety.
SAD: PK of infigratinib and its active metabolites.
SAD: PK of infigratinib and its active metabolites.
Ph2: Safety: TEAEs that lead to dose decrease or discontinuation.
Ph2: Safety: TEAEs that lead to dose decrease or discontinuation.
PH2: PK of infigratinib and its active metabolites.
PH2: PK of infigratinib and its active metabolites.
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).
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).
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.
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.
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).
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).
Extension: Change over time in body length Z-score in relation to ACH tables.
Extension: Change over time in body length Z-score in relation to ACH tables.
次要结局
- 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).
- Ph2: Mean and change from BL in body length Z-score at Week 52 (in relation to ACH tables; BL: values at Day 1).
- Ph2: Mean and change from BL to Week 52 in upper- to lower-body segment ratio.
- Ph2: Mean and change from BL to Week 52 in head circumference/body length ratio.
- Ph2: Health-related quality of life using Infant Toddler Quality of Life (ITQoL).
- Ph2: Milestone development, including social/emotional, language/communication; cognitive; movement/physical development and specific movement strategies used by children with ACH (Ireland 2010).
- Ph2: Skull and brain morphology using magnetic resonance imaging (MRI).
- Ph2: Age at closure of cranial sutures and fontanelles.
- Ph2: Incidence of surgical interventions, including cervical decompression, adenotonsillectomy, and tympanostomy.
- Ph2: Incidence and severity of sleep apnea.
- Ph2: Bone morphology as assessed by bilateral x-rays of lower extremity and whole spine.
- Ph2b: Body length Z-score at Week 52 in relation to ACH tables.
- Ph2b: Mean and change from BL to Week 52 in upper-to lower-body segment ratio.
- Ph2b: Mean and change from BL in head circumference/body length ratio.
- Ph2b: PK of infigratinib and its active metabolites.
- Ph2b: Health-related quality of life using ITQoL.
- Ph2b: Milestone development, including social/emotional, language/communication; cognitive; movement/physical development and specific movement strategies used by children with ACH (Ireland 2010).
- Ph2b: Skull and brain morphology using MRI.
- Ph2b: Age at closure of cranial sutures and fontanelles.
- Extension: Change over time in upper- to lower-body segment ratio.
- Extension: Change over time in head circumference/body length ratio.
- Ph2b: Incidence of surgical interventions, including but not limited to adenotonsillectomy, and tympanostomy.
- Ph2b: Incidence and severity of sleep apnea.
- Ph2b: Bone morphology as assessed by bilateral x-rays of lower extremities and whole spine.
- Extension: Health-related quality of life using ITQoL.
- Extension: Milestone development, including social/emotional, language/communication; cognitive; movement/physical development and specific movement strategies used by children with ACH (Ireland 2010).
- Extension: Age at closure of cranial sutures and fontanelles.
- Extension: Incidence of surgical interventions, including cervical decompression, adenotonsillectomy, and tympanostomy.
- Extension: Bone morphology as assessed by bilateral x-rays of lower extremity and whole spine.
研究者
QED Clinical Development
Scientific
Qed Therapeutics Inc.