CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of AKCEA-TTR-LRx in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
To evaluate the efficacy of AKCEA-TTR-LRx compared to placebo for 120 weeks in patients with ATTR-CM receiving available standard of care (SoC). For more information, please visit https://www.cardio-ttransform.com/.
- Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
- Eligible Ages
- Between 18 Years and 90 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent. If engaged in sexual relations of child-bearing potential, agree to use 1 highly effective contraceptive method - Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participant's non-pregnant female partner must be using a highly effective contraceptive method - Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy (99mTc -3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99m Tc-pyrophosphate [PYP-Tc], or 99m Tc-hydroxymethylene-diphosphonate [HMDP-Tc]) with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio, centrally confirmed - End-diastolic interventricular septum thickness of > 12 mm on Screening echocardiogram - New York Heart Association (NYHA) class I-III
- Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening - Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease - Monoclonal gammopathy of undetermined significance (MGUS) and/or immunoglobulin free light chain ratio < 0.26 and > 1.65, unless fat, bone marrow, or heart biopsy confirming the absence of light chain by mass spectrometry or immunoelectron microscopy - Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or anticipated liver transplant or LVAD within 1 year after randomization - Current or previous treatment with Tegsedi™ (inotersen) or Onpattro™ (patisiran) or other oligonucleotide or RNA therapeutic (including siRNA) - Current treatment with diflunisal, doxycycline, and/or calcium-channel blocker. Participants receiving any of these agents must respect a wash-out period of 14 days before randomization.
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Double (Participant, Investigator)
|ACKEA-TTR-LRx by subcutaneous injection once every 4 weeks||
|Matching placebo by subcutaneous injection once every 4 weeks||
- Ionis Pharmaceuticals, Inc.
Study ContactIonis Pharmaceuticals
This is a multicenter, double-blind study in up to 750 participants, who will be randomized to receive subcutaneous (SC) injections of either AKCEA-TTR-LRx or placebo once every 4 weeks. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A.