NCT04842032已完成4 期
An Open-label, Multi-center, Single-cohort, Post-marketing Phase 4 Study to Evaluate the Efficacy, Pharmacodynamics, and Safety of the Anti-FGF23 Antibody, KRN23, in Pediatric Chinese Patients With X-linked Hypophosphatemic Rickets/Osteomalacia (XLH)
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 5
- 主要终点
- Change from Baseline (CFB) in mean serum phosphorus level at the end of the dose cycle
研究概览
简要总结
The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in pediatric Chinese patients 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 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female Chinese patients, aged 1 to ≤12 years at ICF signature with radiographic evidence of rickets
- •Diagnosis of XLH supported by either of the following:
- •Confirmed PHEX mutation (prior to the study with historic record) in the patient or a directly related family member with approximate X linked inheritance
- •Serum intact FGF23 level ≥30 pg/mL by Kainos assay at Screening
- •Able to receive conventional therapy (oral phosphate and pharmacologic vitamin D)
- •Biochemical findings associated with XLH: Serum phosphorus <3.0 mg/dL (0.97 mmol/L). Serum phosphorus may be re tested (once only) at least 7 days after discontinuation of therapy, if applicable ([see Section 3.1])
- •Serum creatinine within age-adjusted normal range (based on overnight fasting [minimum 4 hours] values collected at Screening)
- •Serum 25(OH)D above or equal to the lower limit of normal (≥16 ng/mL) at Screening. If 25(OH)D levels are below the normal range, 25(OH)D supplementation will be prescribed. Assuming a patient meets all other eligibility requirements, the patient may be re tested for serum 25(OH)D after a minimum of 7 days of treatment
- •Willing to provide access to prior medical records for the collection of historical growth and radiographic data and disease history
- •Written or verbal assent (as appropriate for the patient and region) by the patient and written informed consent by legally authorized representatives provided after the nature of the study has been explained, and prior to any research-related procedures
- •Be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments, as judged by the investigator or subinvestigator
- •Female patients who have reached menarche must have a negative pregnancy test at Screening and be willing to have additional pregnancy testing during the study. If sexually active, male and female patients must be willing to use an effective method of contraception for the duration of the study and for 12 weeks after the last dose of IP
排除标准
- •Positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibody at Screening
- •Tanner stage 4 or higher through physical examination
- •Height percentile >50% based on country specific norms
- •Use of a pharmacologic vitamin D, its metabolites, or analogs, oral phosphate for treatment of XLH, aluminum hydroxide antacids, acetazolamide, thiazide diuretics, and/or systemic corticosteroids within 7 days prior to Week -14
- •Current or prior use of leuprorelin, triptorelin, goserelin, or other drugs known to delay puberty
- •Use of growth hormone therapy within 12 months before ICF signature
- •Have uncontrolled diabetes mellitus, defined as glycated hemoglobin (HbA1c) >8.5% at Screening
- •Presence of nephrocalcinosis on renal ultrasound Grade 4 based on the following scale:
- •Planned or recommended orthopedic surgery (implantation or removal), including staples, 8 plates, or osteotomy, within the first 40 weeks of the study
- •Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age adjusted normal limits (based on overnight fasting [minimum 4 hours] values collected at the Screening)
- •Evidence of hyperparathyroidism (parathyroid hormone [PTH] levels 2.5 × ULN)
- •Use of medication to suppress PTH (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to ICF signature
- •Presence or history of any condition that, in the view of the investigator or subinvestigator, 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 therapeutic mAb within 90 days prior to ICF signature or history of allergic or anaphylactic reactions to any mAb
- •Presence or history of any hypersensitivity to KRN23 excipients that, in the judgment of the investigator or subinvestigator, places the patient at increased risk for adverse effects
- •Use of any investigational product or investigational medical device within 30 days prior to ICF signature, or need for the use of any investigational agent prior to completion of all scheduled study assessments
- •Other patients who are considered to be ineligible for the study by the investigator or subinvestigator for reasons other than the above
研究组 & 干预措施
KRN23
Experimental
KRN23 0.8 mg/kg starting dose, administered Q2W by SC injection up to Week 64. Before KRN23 treatment, all patients will receive oral phosphate and vitamin D analogs for 12 weeks of Run-in period.
干预措施: KRN23 (Drug)
结局指标
主要结局
Change from Baseline (CFB) in mean serum phosphorus level at the end of the dose cycle
时间窗: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 52, and 64
次要结局
- Change in rickets at Weeks 40 and 64 as examined by the Radiograph Global Impression of Change (RGI-C) global score(Weeks 40 and 64)
- Six-minute walking test (6MWT) results to examine walking ability (total distance; patients ≥5 years at the time of signing the ICF only)(Weeks 0, 24, 40 and 64)
- Six-minute walking test (6MWT) results to examine walking ability (percent of predicted normal; patients ≥5 years at the time of signing the ICF only)(Weeks 0, 24, 40 and 64)
- Change in Rickets Severity Score (RSS) total score at Weeks 40 and 64(Weeks 40 and 64)
- Change in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg score at Weeks 40 and 64(Weeks 40 and 64)
- Change in serum phosphorus over time(Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74)
- Change in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) over time(Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74)
- Change in urinary phosphorus over time(Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74)
- Change in recumbent length/standing height in cm, height for age z scores(Weeks 0, 24, 40 and 64)
- Change in growth velocity from pre-treatment and post-treatment over time(Weeks 0, 24, 40 and 64)
- Change in growth velocity z scores from pre-treatment and post-treatment over time(Weeks 0, 24, 40 and 64)
- Change in alkaline phosphatase (ALP) over time(Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74)
- Change in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR; algorithm method) over time(Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74)
- Ten-item Short Form Health Survey for Children (SF-10) physical domain scores to examine health-related Quality of Life(Weeks 0, 24, 40 and 64)
- Ten-item Short Form Health Survey for Children (SF-10) Psychosocial scores to examine health-related Quality of Life(Weeks 0, 24, 40 and 64)
- Face Pain Scale-Revised (FPS-R) scores to examine health-related Quality of Life(Weeks 0, 24, 40 and 64)
- Patient-Reported Outcomes Measurement Information System (PROMIS) scores to examine health-related Quality of Life(Weeks 0, 24, 40 and 64)
研究者
研究点 (5)
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