A Randomised, Parallel, Double-Blind, Placebo-Controlled Phase 2b Study to Assess the Safety, Tolerability and Efficacy of AZD8233 Treatment in Participants With Hyperlipidaemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 411
- 试验地点
- 1
- 主要终点
- Percentage Change From Baseline on Serum LDL-C
研究概览
简要总结
AZD8233 is a PCSK9-targeted ASO for the reduction of circulating levels of LDL-C. This study aims to evaluate safety, efficacy and tolerability of AZD8233.
详细描述
This is a randomized parallel, double-blind, placebo-controlled Phase 2b study in approximately 376 participants with hyperlipidaemia. The primary objective of the study is to assess the safety and tolerability of AZD8233 as compared with placebo, and the effect of AZD8233 versus placebo on relative change in LDL-C. The study will be conducted at up to 100 sites in up to 8 countries.
The screening period starts up to 28 days before the randomization visit and ends on Day -1. Eligible participants will attend 1 enrollment visit and 15 visits during the treatment period and 2 additional visits during the safety follow up period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 18 to 75 years of age, inclusive, at the time of signing the informed consent
- •Participants who have a fasting LDL-C ≥ 70 mg/dL (1.8 mmol/L) but < 190 mg/dL (4.9 mmol/L) at screening
- •Participants who have fasting triglycerides < 400 mg/dL (< 4.52 mmol/L) at screening
- •Participants are receiving a stable dose (≥ 3 months) of maximally tolerated statin and/or ezetimibe therapy
- •Male or female of non-childbearing potential
- •Signed and dated written informed consent prior to any mandatory study specific procedures, sampling, and analyses
排除标准
- •eGFR < 40 mL/min/1.73m2 using the CKD-EPI
- •History or presence of gastrointestinal, hepatic or renal disease or any other conditions known to interfere with absorption, distribution, metabolism or excretion of drugs
- •Any uncontrolled or serious disease, or any medical (eg,. known major active infection or major haematological, renal, metabolic, gastrointestinal or endocrine dysfunction) or surgical condition that, in the opinion of the investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk (according to the investigator's judgment) if he/she participates in the clinical study
- •Poorly controlled T2DM, defined as HbA1c > 10%
- •Acute ischaemic cardiovascular events including stroke within 30 days, or heart failure with New York Heart Association (NYHA) Class III to IV
- •Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding (frequent bleeding gums or nose bleeds)
- •High-risk of bleeding diathesis or anti-platelet therapy other than low dose aspirin (≤100mg/day).
- •Malignancy within the last 10 years
- •Recipient of any major organ transplant
- •LDL or plasma apheresis within 12 months prior to randomisation
- •Uncontrolled hypertension defined as average supine SBP > 160 mmHg or DBP > 90 mmHg
- •Heart rate after 10 minutes supine rest < 50 or > 100 bpm
- •Any laboratory values with the following deviations at the Screening Visit; test may be repeated at the discretion of the investigator if abnormal:
- •Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV)
- •ALT > 1.5 × ULN
- •AST > 1.5 × ULN
- •TBL > ULN
- •ALP > 1.5 × ULN
- •WBC < lower limit of normal (LLN).
- •Haemoglobin < 12 g/dL in males or < 11 g/dL in females
- •Platelet count ≤ LLN
- •aPTT > ULN or Prothrombin Time > ULN
- •UACR > 11 mg/mmol (100 mg/g)
- •UPCR > 300 mg/g
- •Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG
- •QTcF > 470 ms; high degree atrioventricular (AV)-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias
- •History of drug and/or alcohol abuse or a positive screen for drugs of abuse
- •Use of warfarin, direct or indirect thrombin inhibitors or factor Xa inhibitors
- •Mipomersen, or lomitapide within 12 months prior to randomisation
- •Any fibrate therapy other than fenofibrate; if the participant is on fenofibrate therapy, the dose should be stable for at least 6 weeks prior to randomisation
- •Previous administration of AZD8233/AZD6615) or inclisiran (LEQVIO ® Novartis)
- •Use of evolocumab (REPATHA® Amgen) and alirocumab (PRALUENT® Regeneron) within 3 months of screening
研究组 & 干预措施
AZD8233
AZD8233 for subcutaneous use
干预措施: AZD8233 (Drug)
Placebo
Placebo solution for subcutaneous injection
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage Change From Baseline on Serum LDL-C
时间窗: From baseline to Day 197
Percentage change in Low-density Lipoprotein Cholesterol (LDL-C) from baseline to Day 197.
Number of Subjects With Adverse Events (AEs)
时间窗: On-study includes adverse events with an onset date on or after the date of first dose of IP through study competition, planned visit date Day 281.
Please refer to the adverse event module for specifics.
Vital Signs - Temperature
时间窗: Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.
Mean and standard deviation of Temperature at each scheduled visit by treatment.
Vital Sign - Weight
时间窗: Baseline and Day 281.
Mean and standard deviation of Weight at each scheduled visit by treatment.
Number of Participants With an ECG Determined to be Abnormal and Clinically Significant
时间窗: Baseline, Days 85, 169, 225, and 281.
Number of participants With an ECG Determined to be Abnormal and Clinically Significant at each scheduled visit by treatment
Vital Sign - Systolic Blood Pressure
时间窗: Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.
Mean and standard deviation of Systolic Blood Pressure at each scheduled visit by treatment.
Vital Sign - Diastolic Blood Pressure
时间窗: Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.
Mean and standard deviation of Diastolic Blood Pressure at each scheduled visit by treatment.
Vital Sign - Pulse Rate
时间窗: Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.
Mean and standard deviation of Pulse rate at each scheduled visit by treatment.
Treatment Emergent Platelet Count Abnormalities
时间窗: Treatment emergent includes results after the first dose of IP through study competition, planned visit date Day 281.
Treatment emergent platelet count abnormalities by pre-specified criteria by treatment.
次要结局
- Percentage Change From Baseline on Serum PCSK9(From baseline to Day 197)
- Plasma Concentration of AZD8233(Pre-dose of Day 29, Day 85, Day 141, Day 183, Day 197)
- Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period(Pre-dose of Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 281)