CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
- Conditions
- Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
- Interventions
- Drug: Placebo
- Registration Number
- NCT04136171
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
To evaluate the efficacy of eplontersen compared to placebo in participants with ATTR-CM receiving available standard of care (SoC). For more information, please visit https://www.cardio-ttransform.com.
- Detailed Description
This is a multicenter, double-blind study in approximately 1400 participants, who will be randomized to receive subcutaneous (SC) injections of either eplontersen or placebo once every 4 weeks. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1438
- 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 millimeters (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 alterations in immunoglobulin free light chain (FLC) ratio unless fat, bone marrow, or heart biopsy confirming the absence of light chain and the presence of TTR protein by mass spectrometry or immunoelectron microscopy. For participants with chronic kidney disease (CKD) and without presence of monoclonal protein in blood and urine, the acceptable FLC ratio is 0.26-2.25. Results different from that may be discussed with local hematologist, Investigator and Medical Monitor if the risks associated with the biopsy outweigh the benefits
- 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 ribonucleic acid (RNA) therapeutic (including small interfering ribonucleic acid [siRNA]; does not apply to COVID-19 mitochondrial [mRNA] vaccinations)
- Current treatment with diflunisal, doxycycline, with or without ursodeoxycholic acid, and/or non-dihydropyridine calcium-channel blocker (e.g., verapamil, diltiazem). Participants receiving any of these agents must respect a wash-out period of 14 days before randomization.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Eplontersen-matching placebo by subcutaneous injection once every 4 weeks Eplontersen Eplontersen Eplontersen by subcutaneous injection once every 4 weeks
- Primary Outcome Measures
Name Time Method Composite Outcome of Cardiovascular (CV) Mortality and Recurrent CV Clinical Events up to Week 140 Baseline up to Week 140
- Secondary Outcome Measures
Name Time Method Change From Baseline in the 6-minute Walk Test (6MWT) Distance at Week 121 Baseline to Week 121 The 6MWT is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. The 6MWT provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions.
CV Clinical Events up to Week 140 Baseline up to Week 140 All-Cause Mortality up to Week 140 Baseline up to Week 140 Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at Week 121 Baseline to Week 121 The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item self-administered questionnaire developed to independently measure the participant's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life (QOL) within a 2-week recall period.
The KCCQ tool quantifies the following six (6) distinct domains and two (2) summary scores. KCCQ responses are provided along a rating scale continuum with equal spacing from worst to best, with a higher score equaling a better score.CV Mortality up to Week 140 Baseline up to Week 140
Trial Locations
- Locations (144)
Mayo Clinic - Arizona
🇺🇸Phoenix, Arizona, United States
Altman Clinical and Translational Research Institute Center for Clinical Research
🇺🇸La Jolla, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of California, San Francisco (UCSF) - Medical Center
🇺🇸San Francisco, California, United States
Stanford Hospital
🇺🇸Stanford, California, United States
University of Colorado Hospital - Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
The George Washington Medical Faculty Associates - Foggy Bottom North Pavilion
🇺🇸Washington, District of Columbia, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
Emory Heart and Vascular Center - Emory Clifton Campus
🇺🇸Atlanta, Georgia, United States
Scroll for more (134 remaining)Mayo Clinic - Arizona🇺🇸Phoenix, Arizona, United States