NCT02722798已完成2 期
A Phase 2 Open-Label Trial to Assess the Efficacy and Safety of KRN23 in Patients With Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome and a Post-marketing Study of KRN23 Switched From the Phase 2 Trial
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 主要终点
- serum phosphorus concentration at each test time point
研究概览
简要总结
Before switching to the post-marketing study:
To evaluate the efficacy and safety of KRN23 after its 144-week once every 4 weeks (Q4W) repeated SC administration to Japanese and Korean patients with TIO or ENS by a multicenter, open-label, intraindividual dose adjustment study.
After switching to the post-marketing study:
To evaluate the safety and efficacy of KRN23, which is switched from the investigational product to the post-marketing investigational product, at the approved dose and dosing regimen in subjects who continue treatment after the marketing approval of KRN23 in Japan.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years
- •Diagnosis of Tumor-Induced Osteomalacia(TIO) or Epidermal Nevus Syndrome(ENS) and not amenable to receive surgical excision of the offending tumor/lesion
- •Serum phosphorus level < 2.5 mg/dL
- •Serum FGF23 level ≥ 100 pg/mL
- •Ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate< 2.5 mg/dL
- •Estimated glomerular filtration rate (eGFR) at screening ≥ 60 mL/min/1.73 m2, or eGFR ≥ 30 and < 60 mL/min/1.73 m2 with an evidence of no renal failure related to nephrocalcinosis
- •Corrected serum calcium level < 10.8 mg/dL
- •For female subjects of childbearing potential; negative urine pregnancy test and willingness to undergo additional pregnancy tests during the study
- •Willingness to use an acceptable method of contraception while participating in the study
- •Willingness to provide access to prior medical records to determine eligibility including data on imaging tests, blood chemistry, diagnosis, medication, and surgical history
- •Willingness and ability to cooperatively complete all study procedures, adhere to the visit schedule and follow the investigator's instructions, as considered by the investigator or subinvestigator
排除标准
- •Use of the following drugs within 14 days prior to screening: pharmacologic vitamin D metabolites or analogs, or drugs for treating TIO/ENS including oral phosphate, aluminum hydroxide antacids, acetazolamide, or thiazide diuretics
- •Medication to suppress parathyroid hormone (PTH) within 60 days prior to screening
- •Blood or blood product transfusion within 60 days prior to screening
- •Chemotherapy for TIO or other malignant tumors within 4 months prior to screening
- •History of being positive for human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus antibody
- •Predisposition to infection, or history of recurrent infection or known immunodeficiency
- •Pregnant or breastfeeding at screening or intention to become pregnant during the study; for male subjects, the partner's intention to become pregnant during the study
- •Use of an investigational product or device within 4 months prior to screening, or planning to receive other investigational product before completing all assessments in this study
- •Use of therapeutic monoclonal antibodies including KRN23 within 90 days prior to screening
- •History of allergic or anaphylactic reactions to KRN23, any of the KRN23 ingredients, or any other monoclonal antibodies
- •Anyone otherwise considered unsuitable participation in the study by the investigator or subinvestigator
- •At the time of switching to the post-marketing study:
- •Voluntary written informed consent to participate in the post-marketing study (if aged < 20 years at the time of consent, written informed consent must be obtained from his or her legally acceptable representative as well)
- •Switching to the post-marketing study is necessary and appropriate for the subject from the viewpoint of efficacy and safety, as judged by the investigator or subinvestigator.
研究组 & 干预措施
KRN23
Experimental
Subjects will receive subcutaneous injections of KRN23 every 4 weeks from Week 0 through Week 224
干预措施: KRN23 (Drug)
结局指标
主要结局
serum phosphorus concentration at each test time point
时间窗: up to week 224
次要结局
- change from baseline in 1,25(OH)2D(up to week 224)
- Effect to 6 minute walking test (6MWT)(up to week 224)
- Change from Baseline in Serum Phosphorus Level(up to week 224)
- Achievement Proportion of Mid-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L])(at week 24)
- Effect to patient reported outcomes(up to week 224)
- Achievement Proportion of End-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L])(at week 48)
- Changes from baseline over time in serum Type I Collagen C-Telopeptides (CTx)(up to week 224)
- Changes from baseline over time in serum Procollagen 1 N-Terminal Propeptide (P1NP)(up to week 224)
- Changes from baseline over time in serum Bone Specific Alkaline Phosphatase (BALP)(up to week 224)
- Changes from baseline over time in serum Osteocalcin (OC)(up to week 224)
- change from baseline in FGF23(up to week 224)
- change from baseline in alkaline phosphatase(up to week 224)
- change from baseline in urine P(up to week 224)
- change from baseline in tubular reabsorption of phosphate(up to week 224)
- change from baseline in ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate(up to week 224)
- change from baseline in skeletal disease/osteomalacia through trans-iliac crest bone biopsy(up to week 224)
- Effect to Sit to Stand (STS) test(up to week 224)
- Effect to Hand Held Dynamometry (HHD)(up to week 224)
- Effect to Weighted Arm Lift (WAL) test(up to week 224)
- maximum concentration (Cmax) of KRN23(up to week 224)
- area under the curve (AUC) of KRN23(up to week 224)
- time to peak (tmax) of KRN23(up to week 224)
研究者
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