A Double-blind, Randomized, Placebo-controlled, Single-dose Escalation and Multi-dose Escalation Clinical Study Evaluating the Safety, Tolerability, and Efficacy of MT1013 in Hemodialysis Subjects With Secondary Hyperparathyroidism, Along With a Single-arm Study Assessing the Long-term Efficacy and Safety of MT1013
概览
- 阶段
- 2 期
- 干预措施
- Single ascending doses of MT1013
- 疾病 / 适应症
- Secondary Hyperparathyroidism (SHPT) in Subjects With Chronic Kidney Disease (CKD) on Hemodialysis
- 发起方
- Shaanxi Micot Pharmaceutical Technology Co., Ltd.
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- SAD/MAD :Percentage of treatment-emergent adverse events (TEAEs)
- 状态
- 已完成
- 最后更新
- 2个月前
概览
简要总结
A multicenter, Phase II, randomized, double-blind, single ascending dose (SAD) and multiple ascending dose (MAD), as well as single-arm clinical study evaluating the long-term efficacy and safety of MT1013 in hemodialysis subjects with secondary hyperparathyroidism. The SAD study consists of five cohorts at doses of 5, 10, 20, 40, and 60 mg. The MAD study consists of three cohorts at doses of 5, 10, and 20 mg. In both the SAD and MAD studies, each cohort includes 8 subjects (6 subjects receive the active investigational drug, and 2 subjects receive matching placebo), and the cohorts are conducted sequentially. In the long-term dosing cohort, all subjects will undergo regular hemodialysis three times per week, receiving the drug once after each hemodialysis session for a total duration of 52 weeks
研究者
入排标准
入选标准
- •(Subjects must meet all of the following criteria to participate in the trial):
- •Male or non- pregnant, non-lactating female aged 18 to 80;
- •The patient has been on stable, adequate hemodialysis treatment for \>3 months prior to screening;
- •Intact parathyroid hormone (iPTH) level of at least 300 pg/mL;
- •Serum calcium (corrected serum calcium if albumin \<40 g/L) ≥2.25 mmol/L (9.0mg/dL);
- •Hemoglobin ≥ 8.0 g/dL;
- •Subject is clinically stable, as judged by medical history, physical examination, and routine laboratory tests, apart from chronic renal failure;
- •Able to understand and willing to sign the written informed consent form;
- •Women of childbearing potential must have a negative pregnancy test result prior to enrollment, or be postmenopausal for at least 1 year, or be permanently sterile(i.e., documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) for ≥6 weeks. Fertile men with partners of childbearing potential and women of childbearing potential must use effective contraception (i.e., any combination of two of the following: male or female condom with spermicidal gel,diaphragm, sponge, or cervical cap with spermicidal gel) from signing the informed consent until 90 days after MT1013 infusion.
- •Postmenopausal is defined as:
排除标准
- •(Subjects meeting any of the following criteria will be excluded from the study):
- •1 .History of severe ventricular arrhythmia or symptomatic ventricular arrhythmia at screening, or QTc \>470 ms for males or \>480 ms for females at screening;
- •2\. Subjects with heart failure symptoms，class III or IV by New York Heart Association (NYHA) ， at screening;
- •3\. History of myocardial infarction, coronary angioplasty, or coronary artery bypass graft within the past 6 months;
- •4\. History of seizures or having received treatment for seizures;
- •5\. Prior parathyroidectomy;
- •6\. Serum transaminases (alanine aminotransferase, aspartate aminotransferase) \>3 times the upper limit of normal at screening; or serum albumin \<30 g/L;
- •7.History of organ transplant (excluding being on the kidney transplant waiting list), hematopoietic stem cell transplant, or bone marrow transplant; or patients planning to undergo organ transplantation;
- •8.Severe uncontrolled hypertension, defined as systolic blood pressure \>180 mmHg and diastolic blood pressure \>100 mmHg despite optimal medical therapy before enrollment;
- •9.Known malignancy or other comorbidities with a life expectancy of \<3 months (except for patients disease-free for ≥5 years, or disease-free for ≥5 years after the last dose of chemotherapy );
研究组 & 干预措施
MT1013 for SAD
Single ascending doses of MT1013
干预措施: Single ascending doses of MT1013
Placebo for SAD
Placebo comparator for SAD
干预措施: Single ascending doses of MT1013
MT1013 for MAD
Multiple ascending doses of MT1013
干预措施: Multiple ascending doses of MT1013
Placebo for MAD
Placebo comparator for MAD
干预措施: Multiple ascending doses of MT1013
Long-term Dosing Cohort
Dose titration period covers the first 10 weeks , followed by maintenance dosing period, for a total treatment duration of 52 weeks
干预措施: Long-term Dosing Cohort
结局指标
主要结局
SAD/MAD :Percentage of treatment-emergent adverse events (TEAEs)
时间窗: SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2
To investigate the safety and tolerability of MT1013 by assessing the incidence and severity of TEAEs in Single Ascending Dose (SAD Cohort) and Multiple Ascending Doses (MAD Cohort)
Long-term Dosing Cohort: Proportion of subjects with > 30% reduction in serum iPTH compared to baseline level.
时间窗: 14 weeks
Proportion of subjects achieving a \>30% reduction in serum iPTH from baseline at Week 14.
次要结局
- Change in the mean serum intact parathyroid hormone (iPTH) from baseline(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2. Long-term Dosing Cohort: 52 weeks)
- Proportion of subjects achieving a >30% reduction in serum iPTH from baseline(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2. Long-term Dosing Cohort: 52 weeks)
- Change from baseline in corrected Ca(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2. Long-term Dosing Cohort: 52 weeks)
- Change from baseline in ionized calcium(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2)
- Change in DXA-measured bone mineral density (BMD) at the femoral neck and lumbar spine from baseline(Long-term Dosing Cohort: 52 weeks)
- Incidence and severity of treatment-emergent adverse events (TEAEs)(Long-term Dosing Cohort: 52 weeks)
- Change from baseline in serum phosphorus(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2)
- Change from baseline in the mean corrected calcium-phosphorus product(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2)
- Assessment change of Bone Turnover Markers - Change from Baseline(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2. Long-term Dosing Cohort: 52 weeks)
- Cmax of MT1013(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2)
- Tmax of MT1013(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2)
- T1/2 of MT1013(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2)
- AUC0-tau of MT1013(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2)
- AUC0-t of MT1013(SAD：on Day 8±1. MAD：on Day 16+2 or 30+2 and Day 21±2 or 35±2)