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Antisense Oligonucleotide
ION-682884 for Transthyretin Amyloid Cardiomyopathy
Phase 2
Waitlist Available
Research Sponsored by Brigham and Women's Hospital
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial Must have
Age 65-85 years
Only patient who have completed 24 months of therapy in the open label clinical trial of inotersen, "A 24-month open-label study of the tolerability and efficacy of an antisense oligonucleotide (inotersen) in patients with transthyretin (TTR) amyloid cardiomyopathy" (Protocol #:2018-P001436) will be enrolled. All patients in that study had either wild-type transthyretin amyloidosis (ATTRwt) or mutant transthyretin amyloidosis (ATTRm) cardiac amyloidosis, defined by standard criteria.
Must not have
Cardiomyopathy not primarily caused by amyloidosis, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease
If receiving oral anticoagulants (except vitamin K antagonists), the dose must have been stable for 4 weeks prior to the first dose of Study Drug and regular monitoring must be performed, per clinical practice during the study. If the patient is receiving vitamin K antagonists (e.g., warfarin) INR should be in therapeutic range, as established by the Investigator, for 4 weeks prior to the first dose
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 48 months
Awards & highlights
No Placebo-Only Group
Summary
This trial involves injecting a special medicine under the skin to reduce a harmful protein in older patients with heart issues due to abnormal protein deposits. The medicine works by lowering the levels of a protein that can damage the heart.
Who is the study for?
This trial is for patients aged 65-85 with TTR amyloid cardiomyopathy who have completed a previous 24-month inotersen study. They must be stable (NYHA class I-III), able to self-administer injections, and willing to take Vitamin A supplements. Excludes those with severe heart issues, uncontrolled infections or arrhythmias, certain kidney conditions, blood disorders, high bilirubin levels, recent major cardiovascular events or surgeries.
What is being tested?
The trial tests the drug ION-682884's ability to slow down or stop heart damage caused by TTR amyloid deposits. It involves subcutaneous injections every four weeks and compares results against historical data using advanced cardiac imaging techniques over an open-ended period until FDA approval or discontinuation.
What are the potential side effects?
While specific side effects of ION-682884 are not listed here, similar drugs can cause injection site reactions, liver problems (like raised enzyme levels), potential kidney issues reflected in urine protein levels, and may require Vitamin A supplementation due to its reduction.
Eligibility Criteria
Inclusion Criteria
You may be eligible if you check “Yes” for the criteria belowSelect...
I am between 65 and 85 years old.
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I completed 24 months in the inotersen study for TTR amyloid cardiomyopathy.
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I am willing to take Vitamin A supplements during and 3 months after the study.
Exclusion Criteria
You may be eligible for the trial if you check “No” for criteria below:Select...
My heart condition is not mainly due to amyloidosis.
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My blood thinner medication dose has been stable for 4 weeks, and I am monitored regularly.
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I haven't had major heart issues or surgeries in the last 4 weeks.
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I have been diagnosed with leptomeningeal amyloidosis.
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I have a condition that affects my blood's ability to clot.
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I have had or will have a liver or heart transplant, or need a LVAD within a year.
Select...
I have a serious heart valve problem that hasn't been treated.
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I need considerable assistance and medical care.
Select...
I have been diagnosed with AL amyloidosis.
Timeline
Screening ~ 3 weeks3 visits
Treatment ~ Varies
Follow Up ~ 48 months
Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~48 months
Treatment Details
Study Objectives
Study objectives can provide a clearer picture of what you can expect from a treatment.Primary study objectives
Change in cardiac MRI
Echocardiographic change
change in 6 minute walk
+3 moreSecondary study objectives
Response of transthyretin levels to therapy
Side effect profile: platelets
Side-effect profile: renal function
+1 moreAwards & Highlights
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.
Trial Design
1Treatment groups
Experimental Treatment
Group I: Drug subcutaneous injectionExperimental Treatment1 Intervention
Monthly injection of ION 682884, administered subcutaneously at a dose of 45 mg.
Research Highlights
Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
The most common treatments for Transthyretin Amyloid Cardiomyopathy (ATTR-CM) include liver transplantation and antisense oligonucleotides like ION-682884. Liver transplantation aims to remove the source of the amyloidogenic protein in hereditary ATTR by replacing the liver, which produces the mutant transthyretin (TTR).
However, this approach is not effective for wild-type ATTR. Antisense oligonucleotides, such as ION-682884, work by reducing the production of transthyretin in the liver, thereby decreasing the availability of misfolded TTR monomers that form amyloid deposits in the heart.
This reduction in amyloid deposits can slow or halt the progression of cardiac damage, which is crucial for improving the quality of life and prognosis for patients with ATTR-CM.
Troponin-tropomyosin abnormalities in hamster cardiomyopathy.Combinatorial Treatment of Human Cardiac Engineered Tissues With Biomimetic Cues Induces Functional Maturation as Revealed by Optical Mapping of Action Potentials and Calcium Transients.Intracoronary Sarcoplasmic Reticulum Calcium-ATPase Gene Therapy in Advanced Heart Failure Patients with reduced Ejection Fraction: A Prospective Cohort Study.
Troponin-tropomyosin abnormalities in hamster cardiomyopathy.Combinatorial Treatment of Human Cardiac Engineered Tissues With Biomimetic Cues Induces Functional Maturation as Revealed by Optical Mapping of Action Potentials and Calcium Transients.Intracoronary Sarcoplasmic Reticulum Calcium-ATPase Gene Therapy in Advanced Heart Failure Patients with reduced Ejection Fraction: A Prospective Cohort Study.
Find a Location
Who is running the clinical trial?
Brigham and Women's HospitalLead Sponsor
1,666 Previous Clinical Trials
11,843,449 Total Patients Enrolled
Rodney H FalkStudy DirectorBrigham and Women's Hospital
Media Library
Eligibility Criteria:
This trial includes the following eligibility criteria:- Your ALT or AST levels are more than double the normal limit.I am between 65 and 85 years old.My doctor advised against immunosuppressive therapy for me.I am currently on treatment for an infection that won't be finished by the start of the study.My heart condition is not mainly due to amyloidosis.I haven't had cancer in the last 5 years, except for certain skin, prostate, breast, or cervical cancers.I am a man or a woman who is not pregnant or breastfeeding. If I am a man with a premenopausal partner, we use contraception.Your thyroid function tests show a problem that the doctor thinks is important.I completed 24 months in the inotersen study for TTR amyloid cardiomyopathy.I do not have blood in my urine due to kidney issues or untreated bladder cancer.My blood thinner medication dose has been stable for 4 weeks, and I am monitored regularly.I am willing to go back to the hospital for check-ups.I haven't had major heart issues or surgeries in the last 4 weeks.Your blood pressure is very high and not well controlled.Your platelet count is less than 125,000 per microliter of blood.If the ratio of protein to creatinine in your urine is very high, you may not be eligible for the study. If the level is high, it will be checked again to make sure.I have MGUS or abnormal FLC ratio, but no TTR protein in my biopsies.I have been diagnosed with leptomeningeal amyloidosis.My kidney function is significantly reduced.Your HbA1c level is higher than 9.5%.I have a condition that affects my blood's ability to clot.I have had or will have a liver or heart transplant, or need a LVAD within a year.I have a serious heart valve problem that hasn't been treated.My bilirubin levels are high, but it's due to Gilbert's disease and my liver enzymes are normal.You have tested positive for HIV, hepatitis C, or hepatitis B.I need considerable assistance and medical care.I am willing to take Vitamin A supplements during and 3 months after the study.I have been diagnosed with AL amyloidosis.
Research Study Groups:
This trial has the following groups:- Group 1: Drug subcutaneous injection
Awards:
This trial has 1 awards, including:- No Placebo-Only Group - All patients enrolled in this study will receive some form of active treatment.
Timeline:
This trial has the following timeline:- Screening: It may take up to 3 Weeks to process to see if you qualify in this trial.
- Treatment: The duration you will receive the treatment varies.
- Follow Ups: You may be asked to continue sharing information regarding the trial for 6 Months after you stop receiving the treatment.