PER-040-20招募中未知
HELIOS-B: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF VUTRISIRAN IN PATIENTS WITH TRANSTHYRETIN AMYLOIDOSIS WITH CARDIOMYOPATHY (ATTR AMYLOIDOSIS WITHCARDIOMYOPATHY)
Alnylam Pharmaceuticals, Inc.,0 个研究点目标入组 0 人开始时间: 2020年10月16日最近更新:
适应症
试验速览
- 阶段
- 未知
- 状态
- 招募中
- 发起方
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
入选标准
- •1. Age 18 (or age of legal consent per local regulations, whichever is older) to 85 years, inclusive.
- •Patient and Disease Characteristics
- •2. Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy:
- •a. Hereditary ATTR (hATTR) amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria:
- •i. Documentation of a TTR pathogenic mutation consistent with hATTR
- •amyloidosis.
- •ii. Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness >12 mm (based on central echocardiogram reading at Screening).
- •iii. Amyloid deposits in cardiac or noncardiac tissue (eg, fat pad aspirate, salivary gland, median nerve connective sheath) confirmed by Congo Red (or equivalent) staining OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid [DPD-Tc] or 99mTc-pyrophosphate [PYP-Tc]) with Grade 2 or 3 cardiac uptake (centrally confirmed), if monoclonal gammopathy of undetermined significance (MGUS) has been excluded.
- •iv. If the patient has evidence of a MGUS based on serum and urine protein electrophoresis and serum free light chains, documentation of TTR protein in tissue with immunohistochemistry or mass spectrometry is required.
- •b. Wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria:
- •i. Documentation of absence of pathogenic TTR mutation.
- •ii. Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness >12mm (based on central echocardiogram reading at Screening).
- •iii. Amyloid deposits in cardiac tissue with TTR protein identification by IHC, mass spectrometry, OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc] or 99mTc-pyrophosphate [PYP-Tc]) with Grade 2 or 3 cardiac uptake centrally confirmed, if MGUS has been excluded.
- •iv. If the patient has evidence of a MGUS based on serum and urine protein electrophoresis and serum free light chains, documentation of TTR protein in tissue with immunohistochemistry or mass spectrometry is required.
- •2. Medical history of HF with at least 1 prior hospitalization for HF (not due to arrhythmia or a conduction system disturbance treated with a permanent pacemaker) OR clinical evidence of HF (with or without hospitalization) manifested by signs and symptoms of volume overload or elevated intracardiac pressures (eg, elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that currently requires treatment with a diuretic.
- •3. Patient meets one of the following criteria:
- •a. Tafamidis-naïve and not actively planning to commence treatment with tafamidis during the first 12 months following randomization (per exclusion criterion #7) (Note: in addition to patients who have never taken tafamidis, those who have previously been on tafamidis for ≤30 days total and have not received any tafamidis in the past 6 months will be considered tafamidis-naïve for purposes of this study); or
- •b. On tafamidis (Note: must be on-label use of commercial tafamidis per the approved indication and dose in the country of use)
- •4. Patient is clinically stable, with no CV-related hospitalizations within 6 weeks prior to randomi
排除标准
- •Disease-specific Conditions
- •1. Has known primary amyloidosis or leptomeningeal amyloidosis.
- •2. NYHA Class IV heart failure; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3 (defined as NT-proBNP >3000 ng/L and eGFR <45 ml/min).[Gillmore 2018]
- •3. Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV (requires cane or stick to walk due to polyneuropathy, or is wheelchair bound) at the Screening visit.
- •Laboratory Assessments
- •4. Has any of the following laboratory parameter assessments at Screening:
- •a. AST or ALT levels >1.5 × ULN,
- •b. Total bilirubin >1.5 × ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert’s syndrome are eligible if the total bilirubin is <2 × ULN)
- •c. International normalized ratio (INR) >1.5 (unless patients were on anticoagulant therapy in which case excluded if INR ˃3.5)
- •5. Has eGFR <30 mL/min/1.73 m2 (using the modification of diet in renal disease [MDRD] formula) at Screening.
- •6. Has known human immunodeficiency virus infection; or evidence of current or chronic hepatitis C virus or hepatitis B virus infection.
- •Prior/Concomitant Therapy
- •7. Tafamidis-naïve patients (at baseline) for whom the Investigator actively plans or anticipates commencing treatment with tafamidis during the first 12 months following randomization, taking into consideration clinical status, patient preference and/or commercial availability of tafamidis.
- •8. Received prior TTR-lowering treatment (including revusiran, patisiran or inotersen) or participated in a gene therapy trial for hATTR amyloidosis.
- •9. Is currently taking diflunisal; if previously on this agent, must have at least a 3-month wash-out prior to dosing (Day 1).
- •10. Is currently taking doxycycline or tauroursodeoxycholic acid; if previously on any of these agents, must have completed a 30-day wash-out prior to dosing (Day 1).
- •11. Unwilling to avoid any concurrent treatment with diflunisal, tauroursodeoxycholate/doxycycline, or TTR lowering agents (eg, patisiran, inotersen)
- •12. Current or future participation in another investigational device or drug study, scheduled to occur during this study, or has received an investigational agent or device within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to dosing (Day 1). In the case of investigational TTR stabilizer drugs, washout for 3 months prior to dosing (Day 1) is required; this does not apply to patients who are on tafamidis at baseline (per inclusion criterion #4).
- •13. Requires treatment with or is unwilling to avoid any concurrent treatment with nondihydropyridine calcium channel blockers (eg, verapamil, diltiazem).
- •Medical Conditions
- •14. Other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzymes and ECG changes)
- •that the Investigator feels is a significant contributor or the predominant cause of the patient’s heart failure.
- •15. Unstable congestive heart failure (CHF) (including patients who require adjustment of existing diuretics or addition of new diuretics at time of screening for purposes of achieving optimal management of CHF).
- •16. Had acute coronary syndrome or unstable angina within the past 3 months.
- •17. Has history of sustained ventricular tachycardia
研究者
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