A Study to Evaluate the Effectiveness and Safety of AKCEA-TTR-LRx in Patients with ATTR CM

Overview

About this study

To evaluate the effectiveness 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/.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 5/10/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Daniel Borgeson, M.D.

Closed for enrollment

Contact information:

Grace Lin M.D., M.B.A.

(507) 284-8846

Lin.Grace@mayo.edu

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Julie Rosenthal, M.D.

Closed for enrollment

Contact information:

Julieta Williams

(480) 342-1785

Williams.Julieta@mayo.edu

More information

Publications

Publications are currently not available