NCT04516291已完成2 期
A Phase 2b Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Ranging Study to Assess the Efficacy, Safety, and Tolerability of Vupanorsen (PF-07285557) in Statin-Treated Participants With Dyslipidemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 286
- 试验地点
- 112
- 主要终点
- Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24
研究概览
简要总结
This is a multicenter, Phase 2b, double-blind, placebo-controlled, parallel group study to provide data on efficacy, safety, tolerability, and pharmacokinetics (PK) of PF-07285557 (hereafter, vupanorsen) administered subcutaneously (SC) at various doses and regimens in participants with dyslipidemia, defined in this study as participants with elevated non-HDL-C and TG who are receiving a stable dose of a statin.
This study is also known as TaRgeting ANGPTL3 with an aNtiSense oLigonucleotide in AdulTs with dyslipidEmia (TRANSLATE-TIMI 70).
详细描述
This study is intended to enable selection of a dose(s) for future development of vupanorsen for cardiovascular (CV) risk reduction and hypertriglyceridemia.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged ≥40 years at Screening.
- •Fasting non-HDL-C at Screening ≥100 mg/dL.
- •Fasting TG at Screening of 150 to 500 mg/dL, inclusive, which may be repeated once if deemed necessary.
- •Participants must be on a stable dose of a statin for at least 1 month before Screening and plan to remain on the same medication and dose for the duration of the study.
- •Body weight ≥50 kg and ≤136 kg at Screening.
- •Capable of giving signed informed consent.
排除标准
- •Participant has active liver disease (other than NAFLD or NASH, which are permitted), including chronic active hepatitis B or C or primary biliary cirrhosis.
- •Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg). Note: participants who are on an anti-hypertensive medication to treat hypertension should be on a stable dose at least 1 month prior to Screening. The investigator should ensure participant took anti-hypertensive medication as prescribed prior to evaluation of blood pressure.
- •Participant with a known bleeding diathesis or coagulation disorder.
- •Participants with ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the central laboratory and confirmed by a single repeat test, if deemed necessary: HbA1c ≥9.5% eGFR <30 mL/min/1.73 m2 (as determined by the CKD-Epi equation) ALT or AST >2 × ULN Total bilirubin ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ULN Platelet count <LLN
- •History of clinically significant acute cardiac event within 3 months before Screening (includes ischemic stroke, transient ischemic attack, myocardial infarction, revascularization procedures, hospitalization for heart failure).
- •Presence of New York Heart Association Functional Classification IV heart failure symptoms at Screening.
- •Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
- •Current history of alcoholism or drug addiction according to Diagnostic and Statistical Manual of Mental Disorders IV criteria within 12 months prior to Screening. Use of any recreational drugs within 12 months prior to Screening.
- •Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- •Prior/Concomitant Therapy:
- •Prior treatment at any time with vupanorsen.
- •Prior treatment with any oligonucleotide (including small interfering ribonucleic acid) within 6 months of Screening or prior treatment with inclisiran within 12 months of Screening.
- •Use of TG lowering medication (eg, Vascepa [icosapent ethyl]), non-prescription dietary supplements (eg, fish oil) or other cholesterol lowering medication (eg, fibric acid derivatives, niacin, PCSK9 inhibitors, bile acid sequestrants, bempedoic acid) 30 days prior to Screening, other than statins and ezetimibe.
- •Use of warfarin or other coumarins, direct thrombin inhibitors, Factor Xa inhibitors, heparins or heparinoids 30 days prior to Screening.
- •Prior/Concurrent Clinical Study Experience:
- •Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
- •Diagnostic Assessments:
- •Participant has a clinically significant ECG abnormality during the Screening Period that requires further diagnostic evaluation or intervention (eg, new, clinically significant arrhythmia or a conduction disturbance).
- •Other Exclusions
- •Unstable weight (>5% shift in past month) or plan to start a diet for the purpose of significant weight loss.
- •Hypersensitivity to the active substance or to any of the excipients or GalNAc.
- •Any major surgery, including bariatric surgery, within 3 months of Screening.
- •Participants with conditions contraindicated for MRI procedures including pacemakers or aneurysm clips; the presence of MRI incompatible implanted devices; metallic foreign bodies; metal tattoos (including permanent make-up); or severe claustrophobia impacting the ability to perform MRI. Participants who may require mild sedative or anxiolytic in order to complete the MRI may be enrolled.
- •Participants unwilling or unable to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
- •Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
研究组 & 干预措施
Placebo
Placebo Comparator
No drug
干预措施: Placebo (Drug)
Vupanorsen 80 mg every 4 weeks
Experimental
80 milligrams (mg) given subcutaneously every 4 weeks.
干预措施: Vupanorsen (Drug)
Vupanorsen 60 mg every 2 weeks
Experimental
60 mg given subcutaneously every 2 weeks.
干预措施: Vupanorsen (Drug)
Vupanorsen 120 mg every 4 weeks
Experimental
120 mg given subcutaneously every 4 weeks.
干预措施: Vupanorsen (Drug)
Vupanorsen 80 mg every 2 weeks
Experimental
80 mg given subcutaneously every 2 weeks.
干预措施: Vupanorsen (Drug)
Vupanorsen 160 mg every 4 weeks
Experimental
160 mg given subcutaneously every 4 weeks.
干预措施: Vupanorsen (Drug)
Vupanorsen 120 mg every 2 weeks
Experimental
120 mg given subcutaneously every 2 weeks.
干预措施: Vupanorsen (Drug)
Vupanorsen 160 mg every 2 weeks
Experimental
160 mg given subcutaneously every 2 weeks.
干预措施: Vupanorsen (Drug)
结局指标
主要结局
Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24
时间窗: Baseline, Week 24
Fasting was required at least 10 hours before blood sample collection. Baseline was calculated using the average of all values obtained at Screening and on Day 1 prior to dosing.
次要结局
- Percent Change From Baseline in TG, ApoB, and LDL-C at Week 24(Baseline, Week 24)
- Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 16(Baseline, Week 16)
- Percent Change From Baseline in ANGPTL3 at Week 24(Baseline, Week 24)
- Percent Change From Baseline in Triglyceride (TG), Apolipoprotein B (ApoB), Low-Density Lipoprotein-Cholesterol (LDL-C), and Non-HDL-C at Week 16(Baseline, Week 16)
研究者
研究点 (112)
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