TerminatedPhase 2

24 Month Open Label Study of the Tolerability and Efficacy of Inotersen in TTR Amyloid Cardiomyopathy Patients

Stopped: recruitment of new patients not possible during Covid 19 epidemic

United States31 participantsStarted 2019-02-28

Plain-language summary

Transthyretin is a protein produced in the liver that transports thyroid hormone and vitamin A. A single substitution of an amino acid in the structure of TTR can result in a relatively unstable protein, the breakdown products of which (predominantly monomers) aggregate abnormally and produce proteinaceous deposits in nerves and the heart. These deposits are known as amyloid and produce progressive nerve and heart damage. Amyloidosis due to a mutant TTR is usually an autosomal dominant and hence is a familial condition. Wild-type TTR is also capable of producing amyloid deposits which predominantly involves the heart (rather than the nervous system) resulting in a progressive decrease in cardiac function with increasing signs of heart failure. This study aims to determine whether subcutaneous injection of an antisense oligonucleotide drug, known as inotersen, that has been specifically designed to reduce production of the protein transthyretin by the liver, can slow or stop the progression of TTR amyloid cardiomyopathy as compared to historical controls, using advanced echocardiography and cardiac MRI. The study also aims to determine the tolerability and safety of this drug when administered over a 24-month period to patients with TTR amyloid cardiomyopathy.

Who can participate

Age range

18 Years – 85 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Patients must have ATTR amyloidosis, defined as is defined as an echocardiographic appearance of left ventricular wall thickness of 13 mm or more, in the absence of uncontrolled hypertension, and with EITHER a positive biopsy for amyloid, which also stains positive for TTR by immunochemistry or mass spectrometry OR a positive cardiac technetium pyrophosphate scan with isotope uptake in the heart equal or greater to rib uptake and with no evidence of a plasma cell dyscrasia. * For patients meeting the above criteria, wild-type TTR amyloidosis (ATTRwt)will be defined as having transthyretin genetic sequencing negative for a mutation. Mutant/hereditary TTR (ATTRh) will be defined as TTR amyloid cardiomyopathy with TTR sequencing showing an amyloidogenic mutation. A positive biopsy can be from any organ, providing that the echocardiographic appearance is typical of amyloidosis. * Patients should, in the opinion of the Investigator, be in a stable state in terms of NYHA class. Class I-III patients will be recruited. * Age 18-85 years * Male, or non-pregnant, non-lactating females. If a woman is premenopausal, or male partners with a premenopausal woman, she/he must be willing to use the following methods of contraception: condoms, oral/hormonal contraception, intrauterine device, diaphragm, or abstinence * Written informed consent to be obtained prior to study treatment * If diagnosis is made by tissue biopsy histochemical diagnosis (positive stains for TTR …

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Systolic strain imaging by echocardiographic

Timeframe: Month 6

Trial details

NCT IDNCT03702829

SponsorBrigham and Women's Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2021-12-31

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