NCT02163577已完成2 期
A Randomized, Open-Label, Dose Finding, Phase 2 Study to Assess the Pharmacodynamics and Safety of the Anti-FGF23 Antibody, KRN23, in Pediatric Patients With X-linked Hypophosphatemia (XLH)
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 9
- 主要终点
- Change From Baseline in RSS Total Score Over Time
研究概览
简要总结
The objectives of the study are to:
- Identify a dose and dosing regimen of burosumab, based on safety and pharmacodynamic (PD) effect, in pediatric XLH participants
- Establish the safety profile of burosumab for the treatment of children with XLH including ectopic mineralization risk, cardiovascular effects, and immunogenicity profile
- Characterize the pharmacokinetic (PK)/PD profile of the KRN23 doses tested in the monthly (Q4) and biweekly (Q2) dose regimens in pediatric XLH patients
- Determine the PD effects of burosumab treatment on markers of bone health in pediatric XLH patients
- Obtain a preliminary assessment of the clinical effects of burosumab on bone health and deformity, muscle strength, and motor function
- Obtain a preliminary assessment of the effects of burosumab on participant-reported outcomes, including pain, disability, and quality of life in pediatric XLH patients
- Evaluate the long-term safety and efficacy of burosumab
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 5 - 12 years, inclusive, with open growth plates
- •Tanner stage of 2 or less based on breast and testicular development
- •Diagnosis of XLH supported by ONE 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 FGF23 level > 30 pg/mL by Kainos assay
- •Biochemical findings associated with XLH including:
- •Serum phosphorus ≤ 2.8 mg/dL (0.904 mmol/L)*
- •Serum creatinine within age-adjusted normal range*
- •Standing height < 50th percentile for age and gender using local normative data.
- •Radiographic evidence of active bone disease including rickets in the wrists and/or knees, AND/OR femoral/tibial bowing, OR, for expansion subjects, a Rickets Severity Score (RSS) score in the knee of at least 1.5 as determined by central read.
- •Willing to provide access to prior medical records for the collection of historical growth, biochemical and radiographic data, and disease history.
- •Provide written or verbal assent (if possible) and 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.
- •Females who have reached menarche must have a negative pregnancy test at Screening and undergo additional pregnancy testing during the study. If sexually active, male and female subjects must be willing to use an acceptable method of contraception for the duration of the study.
- •Criteria to be determined based on overnight fasting (minimum 4 hours) values collected at Screening Visit 2
- •Use of a pharmacologic vitamin D metabolite or analog (e.g. calcitriol, doxercalciferol, alfacalcidiol, and paricalcitol) within 14 days prior to Screening Visit 2; washout will take place during the Screening Period
- •Use of oral phosphate within 7 days prior to Screening Visit 2; washout will take place during the Screening Period
- •Use of calcimimetics, aluminum hydroxide antacids (e.g. Maalox® and Mylanta®), systemic corticosteroids, and thiazides within 7 days prior to Screening Visit 1
- •Use of growth hormone therapy within 3 months before Screening Visit 1
- •Use of bisphosphonates for 6 months or more in the 2 years prior to Screening Visit 1
- •Presence of nephrocalcinosis on renal ultrasound graded ≥ 3 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 *
- •Evidence of tertiary hyperparathyroidism as determined by the Investigator
- •Use of medication to suppress parathyroid hormone (PTH) (e.g. Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening Visit 1
- •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
- •Previously diagnosed with human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody
- •History of recurrent infection or predisposition to infection, or of known immunodeficiency
- •Use of a therapeutic monoclonal antibody within 90 days prior to Screening Visit 1 or history of allergic or anaphylactic reactions to any monoclonal antibody
- •Presence or history of any hypersensitivity to recombinant human immunoglobulin G1 (IgG1) monoclonal antibody to FGF23 (burosumab) excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects
- •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
- •Criteria to be determined based on overnight fasting (minimum 4 hours) values collected at Screening Visit 2
排除标准
- 未提供
研究组 & 干预措施
Burosumab Q4W Then Q2W
Experimental
Burosumab SC injections every 4 weeks (Q4W). Dose was determined by the participant's weight and prescribed dose by their study doctor. Participants in Q4W were to switch to Q2W beginning with Week 64 dosing.
干预措施: burosumab (Biological)
Burosumab Q2W
Experimental
Burosumab subcutaneous (SC) injections every 2 weeks (Q2W). Dose was determined by the participant's weight and prescribed dose by their study doctor.
干预措施: burosumab (Biological)
结局指标
主要结局
Change From Baseline in RSS Total Score Over Time
时间窗: Baseline, Week 40, 64, 160
The RSS system is a 10-point radiographic scoring method that was developed to assess the severity of nutritional rickets in the wrists and knees based on the degree of metaphyseal fraying, cupping, and the proportion of the growth plate affected. Scores are assigned for the unilateral wrist and knee X-rays deemed by the rater to be the more severe of the bilateral images. The maximum total score on the RSS is 10 points and the minimum score is 0, with a total possible score of 4 points for the wrists and 6 points for the knees. Higher scores indicate greater rickets severity.
Change From Baseline in TmP/GFR Over Time
时间窗: Baseline, Week 40, 64, 160
Data for urinary phosphorus and TRP were used in calculation TmP/GFR.
Change From Baseline in Serum 1,25(OH)2D Over Time
时间窗: Baseline, Week 40, 64, 160
Change From Baseline in Serum Phosphorus Over Time
时间窗: Baseline, Week 40, 64, 160
次要结局
- Change From Baseline in CTx Over Time(Baseline, Week 40, 64)
- Change From Baseline in ALP Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in POSNA-PODCI (Normative Score) Transfer and Basic Mobility Scale Scores Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in POSNA-PODCI (Normative Score) Sports/Physical Functioning Scale Scores Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in POSNA-PODCI (Normative Score) Pain/Comfort Scale Scores Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in POSNA-PODCI (Normative Score) Happiness Scale Scores Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in POSNA-PODCI (Normative Score) Global Functioning Scale Scores Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in FEP Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in P1NP Over Time(Baseline, Week 40, 64)
- Change From Baseline in BALP Over Time(Baseline, Week 40, 64, 160)
- Serum Pre-Dose Concentrations of Burosumab(Week 40, 64, 160)
- Radiographic Global Impression of Change (RGI-C) Global Scores Over Time(Baseline, Week 40, 64, 160)
- RGI-C Knee Scores Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in Standing Height Z Score Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in Growth (Sitting Height) Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in Growth Velocity Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in Growth (Standing Height) Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in RSS Knee Scores Over Time(Baseline, Week 40, 64, 160)
- RGI-C Wrist Scores Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in RSS Wrist Scores Over Time(Baseline, Week 40, 64, 160)
- 6MWT Distance (Predicted Percent of Normal) Change From Baseline Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in POSNA-PODCI (Normative Score) Upper Extremity Scale Scores Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in Growth (Arm Length) Over Time(Baseline, Week 40, 64, 160)
- Change From Baseline in Growth (Leg Length) Over Time(Baseline, Week 40, 64, 160)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)(Up to 216 weeks)
研究者
研究点 (9)
Loading locations...
相似试验
招募中
1 期
A Study to Evaluate the Safety, Tolerability, Drug Levels, and Preliminary Efficacy of BMS-986507 Combinations in Adult Participants With Advanced Solid TumorsLung CancerLung CancerBreast CancerNCT06618287Bristol-Myers Squibb416
终止
1 期
Trial of Fulvestrant, MK-0646, and Dasatinib for Metastatic Hormone Receptor-Positive HER2-Negative Breast CancerBreast CancerNCT00903006M.D. Anderson Cancer Center11
已完成
2 期
Phase IIB Dose Ranging Study in Subjects With Moderate to Severe Rheumatoid ArthritisRheumatoid ArthritisNCT02015520CSL Behring143
终止
1 期
A Study to Evaluate Alnuctamab in Combination With Mezigdomide in Participants With Relapsed and/or Refractory Multiple MyelomaMultiple MyelomaNCT06163898Celgene4
终止
1 期
A Study to Evaluate the Pharmacokinetics and Safety of Loncastuximab Tesirine in Participants With Relapsed or Refractory Diffuse Large B-cell Lymphoma or High-grade B-cell Lymphoma With Hepatic Impairment (LOTIS-10)High-grade B-cell LymphomaDiffuse Large B-Cell LymphomaNCT05660395ADC Therapeutics S.A.5