A study to evaluate Patisiran in patients with transthyretin-type amyloidosis with cardiomyopathy (ATTR amyloidosis with cardiomyopathy)

JRCT ID: jRCT2031210085

Registered date:12/05/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: ATTR amyloidosis with cardiomyopathy
• Date of first enrollment: 16/07/2020
• Target sample size: 16
• Countries of recruitment: Argentina,Japan,Denmark,Japan,Belgium,Japan,New Zealand,Japan,Australia,Japan,France,Japan,Portugal,Japan,China Hong Kong,Japan,Brazil,Japan,Netherlands,Japan,Sweden,Japan,Chile,Japan,Bulgaria,Japan,Italy,Japan,Taiwan,Japan,Korea,Japan,United Kingdom,Japan,Czech,Japan,Mexico,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Placebo:
Normal saline (0.9% NaCl) matching volume of patisiran doses will be administered intravenously.
Patisiran:
Patisiran will be administered by intravenous (IV) infusion.

Outcome(s)

• Primary Outcome: Change from baseline at Month 12 in 6-MWT

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

-Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy:
-Patient is clinically stable, with no CV-related hospitalizations within 6 weeks prior to randomization, as assessed by the Investigator.
-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, peripheraledema) that currently requires treatment with a diuretic.
-Able to complete >=150 m on the 6-MWT at screening.
-Screening NT-proBNP >600 ng/L and <8500 ng/L.
-Patient meets one of the following criteria:
a. Tafamidis naive; in addition to patients who have never taken tafamidis, those who have been on tafamidis for <=30 days total and have not received any tafamidis in the 6 months prior to baseline will be considered tafamidis naive and may qualify for the study.
b. Currently on tafamidis (for >=6 months) and has demonstrated disease progression, as determined by the Investigator. (At the time of study entry, tafamidis treatment must be on-label use of commercial tafamidis.)

Exclude criteria

-Has known primary amyloidosis (AL) or leptomeningeal amyloidosis.
->3000 ng/L and estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m2).[Gillmore 2018]
-NYHA Class IV at the Screening visit.
-Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV (requires cane or stick to walk, or is wheelchair bound) at the Screening visit.
-Has eGFR <30 mL/min/1.73 m2 (using the modification of diet in renal disease [MDRD] formula).
-Has known human immunodeficiency virus infection; or evidence of current or chronic hepatitis C virus or hepatitis B virus infection.
-Received prior TTR-lowering treatment (including patisiran) or participated in a gene therapy trial for hATTR amyloidosis.
-Has non-amyloid disease affecting exercise testing (eg, severe chronic obstructive pulmonary disease, severe arthritis, or peripheral vascular disease affecting ambulation).
-Prior or planned heart, liver, or other organ transplant.
-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 electrocardiogram [ECG] changes).

Related Information

• Primary Sponsor: Alnylam Pharmaceuticals, Inc
• Secondary ID(s): NCT03997383