A Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of 9MW3011 in Patients With Non-transfusion-dependent β- Thalassemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Number of subjects with abnormal clinically significant results from physical examination
研究概览
简要总结
This is a phase Ib, randomized, double-blind, placebo-controlled, multiple ascending dose study . The objectives of the study are to evaluate the safety , tolerability, pharmacokinetics(PK), pharmacodynamics(PD), and immunogenicity of 9MW3011 in patients with non-transfusion-dependent β- thalassemia .
详细描述
A total of 40 subjects diagnosed with non-transfusion-dependent β-thalassemia will be enrolled in this study and assigned into four dosage cohorts. In each cohort, subjects will be randomized in a 4:1 ratio to receive 9MW3011 or placebo via intravenous infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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 and female subjects aged 18 to 65 years (inclusive)
- •Subject must have a documented genetic diagnosis of β-thalassemia or hemoglobin E/ β-thalassemia
- •Subjects must meet the criteria for non-transfusion-dependent thalassemia
- •Subjects must have a baseline hemoglobin level between 70-100 g/L(inclusive), based on 2 consecutive measurements taken at least 1 week apart within 4 weeks before randomization
- •Subjects must have evidence of iron overload during screening
- •Subject must have performance status: Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
- •Subjects must fully understand the study procedures and methods, voluntarily participate in the trial, and sign an informed consent form
排除标准
- •Subjects diagnosed with alpha-thalassemia
- •Subjects diagnosed with HbS/beta-thalassemia or transfusion-dependent beta-thalassemia
- •Subjects exhibit severe iron overload at the time of screening
- •In addition to thalassemia, subjects have any other forms of anemia and hematological disorders that the investigator assesses may compromise safety or influence study outcomes
- •Combined with any significant systemic diseases or psychiatric disorders
- •Subjects have New York Heart Association (NYHA) Class III-IV heart failure and other cardiovascular diseases within 6 months prior to screening or currently present
- •During the screening or baseline period, subjects exhibiting a QTcF interval of ≥450ms for males and ≥470ms for females on a 12-lead electrocardiogram (ECG), or presenting an abnormal 12-lead ECG with clinical significance
- •Uncontrolled hypertension before screening
- •A history of malignant neoplasm occurring within the last five years
- •Severe infection requiring hospitalization or intravenous antimicrobial therapy, or uncontrolled systemic bacterial, fungal, or viral active infection
- •Subject have received concomitant treatment that was not permitted by the protocol
- •Subjects whose hematological parameters did not meet the inclusion criteria during screening
- •Subjects with a history of substance abuse, as well as those who yield positive results on substance abuse screening
- •Subjects who are unable to undergo MRI scans
- •Pregnant or lactating women
- •Subjects presenting any other factors deemed unsuitable for participation assessed by the investigator
研究组 & 干预措施
Cohort 1
9MW3011 or placebo (Randomized 4:1)
干预措施: 9MW3011 (Drug)
Cohort 1
9MW3011 or placebo (Randomized 4:1)
干预措施: 9MW3011 placebo (Drug)
Cohort 2
9MW3011 or placebo (Randomized 4:1)
干预措施: 9MW3011 (Drug)
Cohort 2
9MW3011 or placebo (Randomized 4:1)
干预措施: 9MW3011 placebo (Drug)
Cohort 3
9MW3011 or placebo (Randomized 4:1)
干预措施: 9MW3011 (Drug)
Cohort 3
9MW3011 or placebo (Randomized 4:1)
干预措施: 9MW3011 placebo (Drug)
Cohort 4
9MW3011 or placebo (Randomized 4:1)
干预措施: 9MW3011 (Drug)
Cohort 4
9MW3011 or placebo (Randomized 4:1)
干预措施: 9MW3011 placebo (Drug)
结局指标
主要结局
Number of subjects with abnormal clinically significant results from physical examination
时间窗: up to day 169
The physical examinations will include examination of the following: skin and mucous membranes, lymph nodes, head and neck, chest, abdomen, musculoskeletal, nervous system, and other sites of note elicited from the subject.
Number of subjects with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters
时间窗: up to day 169
The examination indicators include heart rate, PR, QRS, uncorrected QT, and QTcF(corrected by Fridericia formula).
Number of subjects with abnormal clinically significant clinical laboratory results
时间窗: up to day 169
Clinical laboratory tests include hematology, urinalysis, blood chemistry, coagulation function.
Adverse Event(including serious adverse event)
时间窗: up to day 169
The incidence of Adverse Events(AEs)and Serious Adverse Events(SAEs)from treatment until the last scheduled follow-up visit
Number of subjects with abnormal vital signs
时间窗: up to day 169
Vital signs measurements will include pulse rate, respiration rate, blood pressure (systolic and diastolic blood pressure) and body temperature.
次要结局
- PD-parameters-hepcidin(up to day 169)
- PD-parameters-serum iron(up to day 169)
- Anti-drug antibody(ADA)(up to day 169)
- Liver iron concentration(LIC)(up to day 169)
- Concentration of 9MW3011 in serum(up to day 169)