A Double-blind, Randomised, Placebo-controlled Study to Assess the Effect of SNF472 on Progression of Cardiovascular Calcification on Top of Standard of Care in End-stage-renal-disease (ESRD) Patients on Hemodialysis (HD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 274
- 主要终点
- Change in Log CAC Volume Score From Baseline to Week 52 for the Combined Dose Groups vs Placebo
研究概览
简要总结
The primary objective is to assess the effect of 2 dose levels of SNF472 (300 mg and 600 mg) compared to placebo on the progression of coronary artery calcium volume score over a 12-month (52 weeks) period in ESRD patients on HD
详细描述
Reducing the progression of cardiovascular calcification (CVC) in HD patients may improve the severe burden of CV disease related to the underlying ESRD. As no therapy is currently indicated to target CVC, there is a need to investigate the ability of SNF472 to reduce CVC progression and, ultimately, to improve CV outcomes in HD patients. This phase 2b double-blind, randomised, placebo-controlled study is designed to assess the effect of SNF472 on the progression of CVC as measured by calcium volume and CAC/Agatston scores in ESRD patients receiving HD. The study hypothesis is that administration of SNF472 over 52 weeks can slow the progression of CVC in this patient population compared to placebo.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male patients, 18 to 80 years (inclusive) of age at randomisation
- •CAC score of 100 to 3500 AU (Agatston Units) inclusive within a 3-week period prior to randomisation as measured by a multi-detector CT scanner
- •Patients who are EITHER ≥ 55 years OR have a history of diabetes mellitus at randomisation
- •Patients on HD for ≥ 6 months prior to randomisation
- •Willing and able to understand and sign the informed consent
排除标准
- •Scheduled date for kidney transplant from a known living donor
- •Weight above 300 lbs (136 kg)
- •Hospitalisation in the previous 3 months prior to randomisation for unstable angina, MI, stroke, transient ischaemic attack, amputation or peripheral or coronary bypass surgery
- •History of unstable heart failure in the previous 3 months, defined as an unplanned presentation to a hospital or dialysis treatment facility with signs/symptoms of acute pulmonary edema and requiring ultrafiltration therapy
- •History of cancer that has been in remission for < 5 years prior to randomisation. A history of basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin is allowed
- •Pregnant or trying to become pregnant, currently breast-feeding, or of child-bearing potential (including peri-menopausal women who have had a menstrual period within one year) and not willing to practice birth control using a double barrier method (criteria apply to women only) at least 30 days post last dose of study medication
- •Hypocalcaemia defined as a serum calcium below 8.0 mg/dL (or 2.0 mmol/L) for the serum calcium most proximal to screening per patient's medical records
- •Extreme elevation in serum phosphorous, defined as a serum phosphorous above 10 mg/dL (or 3.23 mmol/L) within the last 2 months proximal to screening per patient's medical records
- •Uncontrolled hypertension defined as any 2 or more consecutive post-dialysis diastolic blood pressure (DBP) > 100 mmHg within the last 2 months proximal to screening expected survival < 2 years in the Investigator's medical opinion
- •Known active drug or alcohol abuse within 1 year of randomisation
- •Use of other investigational drugs within 30 days of randomisation
- •Non-compliance with dialysis treatment which, in the opinion of the Investigator, evidenced by either repeated missed dialysis treatments or significant non-compliance with the patient's medication regimen
- •Inability to comply with all required study procedures and schedule, inability to speak and read in the protocol-derived language of that patient's clinical site, or unwillingness or inability to give written informed consent
研究组 & 干预措施
SNF472 300 mg
Dose 1 arm (300 mg): 1 vial of physiological saline and 1 vial of active (10 mL SNF472 at 30 mg/mL)
干预措施: SNF472 (Drug)
SNF 472 600 mg
Dose 2 arm (600 mg): 2 vials of active (10 mL SNF472 at 30 mg/mL)
干预措施: SNF472 (Drug)
Matching Placebo
Placebo arm: 2 vials of physiological saline
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Log CAC Volume Score From Baseline to Week 52 for the Combined Dose Groups vs Placebo
时间窗: Baseline (Week 1, Day 1) and Week 52
Coronary Artery Calcification (CAC) Volume Score is a calculation to quantify the calcification of coronary artery calcium without factoring in the calcium density as measured by the CAC Agatston Score. The CAC Score was log-transformed and the primary outcome measure was the change in Log CAC Volume Score from Baseline to Week 52 for the combined dose groups vs placebo. The primary analysis used an ANCOVA model with the change in log volume score (log 52-week volume score - log baseline volume score) as the dependent variable and with a fixed effect term for the combined randomized treatment groups and log CAC volume score at baseline as a covariate. The least squares means for the treatment groups was estimated and back transformed. A smaller change from baseline to follow up is a better outcome.
次要结局
- Change in Log Aortic Valve Calcification Volume Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo(Baseline (Week 1, Day 1) and Week 52)
- Mortality Rate (All-cause) for Each Dose Group and Placebo(Baseline (Week 1, Day 1) and Week 52)
- Change in Log Thoracic Aorta Calcification Volume Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo(Baseline (Week 1, Day 1) and Week 52)
- Number of Subjects With <15% Progression in CAC Agatston Score From Baseline to Week 52 for Each Dose Group and the Combined Dose Groups vs Placebo(Baseline (Week 1, Day 1) and Week 52)
- Change in Log Thoracic Aorta Calcification Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo(Baseline (Week 1, Day 1) and Week 52)
- Change in Log Aortic Valve Calcification Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and the Combined Dose Groups vs Placebo(Baseline (Week 1, Day 1) and Week 52)
- Change in Log CAC Volume Score From Baseline to Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo(Baseline (Week 1, Day 1) and Week 52)
- Change in Log CAC Agatston Score Between Baseline and Week 52 for Each Dose Group (300 mg and 600 mg) vs Placebo and for the Combined Dose Groups vs the Placebo Group(Baseline (Week 1, Day 1) and Week 52)
- Number of Subjects With >=15% Progression in CAC Agatston Score at Week 52 for Each Dose Group and the Combined Dose Groups vs Placebo(Baseline (Week 1, Day 1) and Week 52)
- Number of Participants With the Composite Safety Endpoint (Cardiovascular Death, Nonfatal Myocardial Infarction, Non-fatal Stroke, Heart Failure or Non-fatal Cardiac Arrest.(Baseline (Week 1, Day 1) and Week 52)