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 with Cardiomyopathy)
- Conditions
- Transthyretin Amyloidosis with Cardiomyopathy10082206
- Registration Number
- NL-OMON52969
- Lead Sponsor
- Alnylam Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 22
1. Age 18 (or age of legal consent per local regulations, whichever is
older) to 85 years, inclusive.
2. Documented diagnosis of ATTR amyloidosis with cardiomyopathy,
classified as either hATTR amyloidosis with cardiomyopathy or wtATTR
amyloidosis with cardiomyopathy
3. 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.
4. 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); or
b. On tafamidis (Note: must be on-label use of commercial tafamidis
per an approved cardiomyopathy indication and dose in the country of use)
5. Patient is clinically stable, with no CV-related hospitalizations within 6
weeks prior to randomization, as assessed by the Investigator.
6. Screening NT-proBNP >300 ng/L and <8500 ng/L; in patients with permanent or
persistent atrial fibrillation, screening NT-proBNP >600 ng/L and <8500ng/L.
7. Able to complete >=150 meters on the 6-MWT at Screening.
8. Have a Karnofsky performance status of >=60%.
1. Has known primary amyloidosis (AL 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)
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.
4. Has any of the following laboratory parameter assessments at
Screening:
a. AST or ALT levels >2.0 × ULN,
b. Total bilirubin >2.0 × 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.
7. Tafamidis-naïve patients (per inclusion criteria #4a) for whom the
Investigator
actively plans or anticipates commencing treatment with tafamidis either during
the screening period or 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 30-day wash-out prior to dosing (Day 1).
10. Is currently taking doxycycline or tauroursodeoxycholic acid or
ursodeoxycholic acid; if
previously on any of these agents, must have completed a 30-day washout
prior to dosing (Day 1).
11. Unwilling to avoid any concurrent treatment with diflunisal,
ursodeoxycholic acid/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).
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary outcome is a composite outcome of all-cause mortality and recurrent CV<br /><br>events (CV hospitalizations and urgent HF visits) in both the overall<br /><br>population and the vutrisiran monotherapy subgroup (defined as patients not on<br /><br>tafamidis at study baseline).</p><br>
- Secondary Outcome Measures
Name Time Method <p>The following secondary endpoints will be defined in both the overall<br /><br>population and the vutrisiran monotherapy subgroup:<br /><br>• Change from baseline in 6-minute walk test (6-MWT)<br /><br>• Change from baseline in the Kansas City Cardiomyopathy Questionnaire Overall<br /><br>Summary (KCCQ-OS)<br /><br>• All-cause mortality<br /><br>• Change from baseline in NYHA class</p><br>