An Open-Label, Phase 2 Study to Assess the Safety, Pharmacodynamics, and Efficacy of KRN23 in Children From 1 to 4 Years Old With X-linked Hypophosphatemia (XLH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 6
- 主要终点
- Change From Baseline at Week 40 in Serum Phosphorus
研究概览
简要总结
The primary objectives of the study are to:
- Establish the safety profile of KRN23 for the treatment of XLH in children between 1 and 4 years old
- Determine the PD effects of KRN23 treatment on serum phosphorus and other PD markers that reflect the status of phosphate homeostasis in children between 1 and 4 years old with XLH
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 4 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged ≥1 year and <5 years
- •Diagnosis of XLH supported by ONE or more of the following
- •Confirmed phosphate regulating gene with homology to endopeptidases located on the X chromosome (PHEX) mutation in the patient or a directly related family member with appropriate X-linked inheritance
- •Serum fibroblast growth factor 23 (FGF23) level > 30 pg/mL by Kainos assay
- •Biochemical findings associated with XLH including:
- •Serum phosphorus < 3.0 mg/dL (0.97 mmol/L)
- •Serum creatinine within age-adjusted normal range
- •Radiographic evidence of rickets
- •Willing to provide access to prior medical records for the collection of historical growth, biochemical, and radiographic data and disease history
- •Provide written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures
- •Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule, and comply with the assessments
排除标准
- •Unwilling to stop treatment with oral phosphate and/or pharmacologic vitamin D metabolite or analog (e.g. calcitriol, alfacalcidol) during the screening period and for the duration of the study
- •Presence of nephrocalcinosis on renal ultrasound grade 4 based on the following scale: 0 = Normal, 1 = Faint hyperechogenic rim around the medullary pyramids, 2 = More intense echogenic rim with echoes faintly filling the entire pyramid, 3 = Uniformly intense echoes throughout the pyramid, 4 = Stone formation: solitary focus of echoes at the tip of the pyramid
- •Planned or recommended orthopedic surgery including staples, 8-plates or osteotomy, within the clinical trial period
- •Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted normal limits
- •Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study
- •Presence of a concurrent disease or condition that would interfere with study participation or affect safety
- •History of recurrent infection or predisposition to infection, or of known immunodeficiency
- •Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments
结局指标
主要结局
Change From Baseline at Week 40 in Serum Phosphorus
时间窗: Baseline, Week 40
The Generalized Estimation Equation (GEE) model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with exchangeable covariance structure.
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
时间窗: From first dose of study drug through the end of the study (Week 160). Maximum duration of exposure to study drug was 160 weeks.
An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. A serious AE was defined as an AE that at any dose, in the view of either the Investigator or Sponsor, results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or disability, a congenital anomaly/birth defect, or other important medical events (according to the investigator). An AE was considered a TEAE if it occurred on or after the first dose and was not present prior to the first dose, or it was present prior to the first dose but increased in severity during the study. Events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).
次要结局
- Radiographic Global Impression of Change (RGI-C) Score at Week 40(Week 40)
- Change From Baseline in Rickets at Week 40 as Assessed by the RSS Total Score(Baseline, Week 40)
- Change From Baseline Over Time in Recumbent Length/Standing Height as Assessed by Height-for-Age Z-Scores(Baseline, Weeks 12, 24, 40, 64, 88, 112, 136, 160)
- RGI-C Score at Week 64(Week 64)
- Change From Baseline in Rickets at Week 64 as Assessed by the RSS Total Score(Baseline, Week 64)
- Change From Baseline Over Time in Serum Alkaline Phosphatase (ALP)(Baseline, Weeks 4, 12, 20, 40, 48, 56, 64, 76, 88, 100, 112, 124, 136, 148, 160)
- Percent Change From Baseline Over Time in Serum ALP(Baseline, Weeks 4, 12, 20, 40, 48, 56, 64, 76, 88, 100, 112, 124, 136, 148, 160)
- RGI-C Lower Limb Deformity Score at Week 64(Week 64)
- RGI-C Lower Limb Deformity Score at Week 40(Week 40)
- Change From Baseline Over Time in Recumbent Length/Standing Height(Baseline, Weeks 12, 24, 40, 64, 88, 112, 136, 160)
- Change From Baseline Over Time in Recumbent Length/Standing Height as Assessed by Percentiles(Baseline, Weeks 12, 24, 40, 64, 88, 112, 136, 160)