Have you or your loved ones been diagnosed with transthyretin-mediated amyloid cardiomyopathy (attr cm)?

You may be eligible to participate in a transthyretin-mediated amyloid cardiomyopathy (attr cm) clinical trial.

Have you or your loved ones been diagnosed with transthyretin-mediated amyloid cardiomyopathy (attr cm)? You may be eligible to participate in a transthyretin-mediated amyloid cardiomyopathy (attr cm) clinical trial.

What is a clinical trial? Is participating in a clinical trial right for you? Learn more

Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM) Clinical Trial

NCT04136171 | Phase 3 | Interventional

Have you or your loved ones been diagnosed with transthyretin-mediated amyloid cardiomyopathy (attr cm)?

You may be eligible to participate in a transthyretin-mediated amyloid cardiomyopathy (attr cm) clinical trial.

Recruiting

Male & Female

18 - 90

Years old

This study is looking to recruit 1400 Participants

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.

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Details for the study

Brief Title

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)

Official Title

A Phase 3 Global, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ION-682884 in Patients With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)

Brief Summary

To evaluate the efficacy of eplontersen compared to placebo in participants with ATTR-CM <br /> receiving available standard of care (SoC). For more information, please visit <br /> 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.

Treatments and/or Procedures

Eplontersen

Eplontersen by subcutaneous injection

Placebo

Eplontersen-matching placebo by subcutaneous injection

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Secondary

Change From Baseline in the 6-minute Walk Test (6MWT) Distance at 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.

Baseline to Week 121

Secondary

Change From Baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores at 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.

Baseline to Week 121

Study Criteria

Inclusion Criteria:

  -  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

Exclusion Criteria:

  -  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.