NCT04842019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 Adult Chinese Patients With X-linked Hypophosphatemic Rickets/Osteomalacia
适应症
干预措施
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 18
- 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 adult 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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female Chinese patients, aged 18 to 65 years (inclusive) at the time of signing the ICF
- •Diagnosis of XLH supported by classic clinical features of adult XLH (such as short stature or bowed legs) and at least either of the following at screening:
- •Confirmed PHEX mutation (prior to the study with historic record) in the patient or a directly related family member with appropriate X linked inheritance
- •Serum iFGF23 level ≥30 pg/mL by the Kainos assay at Screening
- •Biochemical findings consistent with XLH following overnight fasting (≥8 hours) at Screening:
- •Serum phosphorus <2.5 mg/dL (0.81 mmol/L). Serum phosphorus level may be re tested (once only) at least 7 days after discontinuation of therapy, if applicable.
- •TmP/GFR of <2.5 mg/dL
- •Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥4 on the BPI Worst Pain question at Screening (Skeletal pain that, in the opinion of the investigator or subinvestigator, is attributed solely to causes other than XLH/osteomalacia [e.g., back pain or joint pain in the presence of severe osteoarthritis by radiograph in that anatomical location] in the absence of any skeletal pain likely attributed to XLH/osteomalacia should not be considered for eligibility)
- •Patients who are taking chronic pain medications (including narcotic pain medications/opioids) must be on a stable regimen for at least 21 days before signing the ICF and be willing to maintain the medications at the same stable dose(s) and schedule throughout the study. The dose must not exceed 60 mg oral morphine equivalents/day
- •Able to receive conventional therapy (oral phosphate and pharmacologic vitamin D [or metabolites/analogs])
- •Written informed consent provided after the nature of the study has been explained and prior to any research related procedures
- •Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history
- •Have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study (female patients of child-bearing potential only)
- •Be willing to use an effective method of contraception while participating in the study (sexually active patients of child bearing potential) and for 12 weeks after last dose of study drug. Women of non child bearing potential are defined as permanently sterile (i.e. due to hysterectomy or bilateral oophorectomy) or postmenopausal (defined as at least 12 months postcessation of menses without an alternative medical cause). Postmenopausal status of female patients will be confirmed with a Screening serum follicle stimulating hormone (FSH) level >40 mIU/mL
- •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
- •Have completed entries for ≥4 of 7 consecutive days of the patient diaries before Week -14
排除标准
- •Use of a pharmacologic vitamin D, its metabolites, or analogs, and oral phosphate for treatment of XLH within 14 days prior to Screening.
- •Use of aluminum hydroxide antacids, acetazolamide, thiazide diuretics and/or systemic corticosteroids within 14 days prior to Week -14
- •Corrected serum calcium level ≥10.8 mg/dL (2.69 mmol/L) at Screening
- •Plasma iPTH ≥2.5 times the upper limit of normal at Screening
- •Uncontrolled diabetes mellitus, defined as HbA1c >7.5% at Screening
- •Use of medication to suppress PTH (e.g., Sensipar®, cinacalcet, calcimimetics) within 60 days before signing the ICF
- •Use of oral bisphosphonates in the 2 years before signing the ICF
- •Planned or recommended orthopedic surgery within the clinical trial period
- •History of traumatic fracture or orthopedic surgery within 6 months before signing the ICF
- •Use of KRN23, or any other therapeutic mAb within 90 days before signing the ICF
- •Use of any investigational product or investigational medical device within 30 days before signing the ICF, or requirement for any investigational agent prior to completion of all scheduled study assessments
- •Pregnant or breastfeeding at Screening or Week -14, or intention to become pregnant (the patient or partner) at any time during the study
- •Unable or unwilling to withhold prohibited medications throughout the study
- •Presence or history of any hypersensitivity, or allergic or anaphylactic reactions to any mAb or KRN23 excipients that, in the judgment of the investigator or subinvestigator, places the patient at increased risk for adverse effects
- •Positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibody at Screening, or prior history of positive test
- •History of recurrent infection or predisposition to infection, or of known immunodeficiency
- •Presence of malignant neoplasm (except basal cell carcinoma)
- •Presence of a concurrent disease or condition that would interfere with study participation or affect safety
- •Presence or history of any condition that, in the view of the investigator or subinvestigator, places the patient at high risk of poor treatment compliance or of not completing the study
研究组 & 干预措施
KRN23
Experimental
KRN23 1 mg/kg administered subcutaneously (SC) every 4 weeks for 48 weeks. 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 4, 8, 12, 16, 20, 24, 36, and 48
次要结局
- Change in BPI Pain Severity score and Pain Interference score over time(Weeks 0, 12, 24, 36, and 48)
- Change in BPI Pain Interference score over time(Weeks 0, 12, 24, 36, and 48)
- Change in Brief Pain Inventory (BPI) Worst Pain score over time(Weeks 0, 12, 24, 36, and 48)
- The proportion of subjects achieving mean serum phosphorus levels above the LLN (2.5 mg/dL [0.81 mmol/L]) at the mid-point of dosing cycle(Weeks 2, 6, 10, 14, 18 and 22)
- The proportion of subjects achieving mean serum phosphorus levels above the lower limit of normal (LLN; 2.5 mg/dL [0.81 mmol/L]) at the end of the dosing cycle(Weeks 4, 8, 12, 16, 20, 24, 36, and 48)
- CFB in mean serum phosphorus level at the mid-time point of dosing cycle(Weeks 2, 6, 10, 14, 18 and 22)
- Mean percent CFB in serum phosphorus levels averaged at the end of dose cycles(Baseline to Week 48)
- Cumulative exposure: area under curve (AUC) of serum phosphorus(Baseline to Week 48)
- Change in serum 1,25(OH)2D over time(Baseline to Week 48)
- Change in urinary phosphorus over time(Baseline to Week 48)
- Change in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR; algorithm method) over time(Baseline to Week 48)
- Change in the health related QOL assessment by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function over time(Weeks 0, 12, 24, 36, and 48)
- Change in the Stiffness and Physical Function domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) over time(Weeks 0, 12, 24, 36, and 48)
研究者
研究点 (5)
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