ION-682884 for Transthyretin Amyloid Cardiomyopathy

Overseen By Sarah Cuddy, MB

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: Inotersen

Must not be taking: Antivirals, Antimicrobials, Anticoagulants

Disqualifiers: Uncontrolled hypertension, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

17 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on oral anticoagulants, the dose must be stable for 4 weeks before starting the study drug, and regular monitoring is required during the study.

What data supports the effectiveness of the drug ION-682884 for treating transthyretin amyloid cardiomyopathy?

The research highlights that tafamidis, a drug for transthyretin amyloid cardiomyopathy, significantly improves survival and reduces hospitalizations. While ION-682884 is not directly mentioned, similar drugs like tafamidis show promising results, suggesting potential effectiveness for ION-682884. ^{1 2 3 4 5}

How does the drug ION-682884 differ from other treatments for transthyretin amyloid cardiomyopathy?

ION-682884 is a novel treatment for transthyretin amyloid cardiomyopathy that may work by silencing the transthyretin gene, which is different from existing treatments like tafamidis that stabilize the transthyretin protein. This approach could potentially prevent the formation of harmful amyloid fibrils in the heart. ^{2 6 7 8 9}

What is the purpose of this trial?

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.

Research Team

Rodney H Falk

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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.

Inclusion Criteria

I am between 65 and 85 years old.

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.

I completed 24 months in the inotersen study for TTR amyloid cardiomyopathy.

Exclusion Criteria

Uncontrolled clinically significant cardiac arrhythmia, per Investigator's assessment (e.g., no pacemaker, although indicated)

Your ALT or AST levels are more than double the normal limit.

My doctor advised against immunosuppressive therapy for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous injections of ION-682884, with follow-up visits at six weeks, 12 weeks, three months, and six months thereafter.

48 months

Monthly visits (in-person), weekly lab draws (home)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with ongoing assessments including echocardiogram, lab work, and cardiopulmonary exercise testing.

Open-ended

Open-label extension

Participants may continue receiving the study drug until FDA approval or study termination.

Open-ended

Treatment Details

Interventions

• ION-682884

Trial Overview 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.

Participant Groups

Group I: Drug subcutaneous injection Experimental Treatment 1 Intervention

Monthly injection of ION 682884, administered subcutaneously at a dose of 45 mg.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), significantly reducing all-cause mortality and cardiovascular-related hospitalizations compared to placebo in the phase III ATTR-ACT trial, which involved patients over a 30-month period.

The treatment was well tolerated with a safety profile similar to placebo, making it a suitable long-term option for patients, and it provides a disease-modifying therapy rather than just symptom management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafamidis: A Review in Transthyretin Amyloid Cardiomyopathy. Lamb, YN.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Prognostic Value of N-Terminal Pro-Brain Natriuretic Peptide and High-Sensitivity Troponin T Levels in the Natural History of Transthyretin Amyloid Cardiomyopathy and Their Evolution after Tafamidis Treatment. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Specific Therapy for Transthyretin Cardiac Amyloidosis: A Systematic Literature Review and Evidence-Based Recommendations. [2021]

3. Japan pubmed.ncbi.nlm.nih.gov

Initial Experience With Tafamidis Treatment for Transthyretin Amyloid Cardiomyopathy. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Transthyretin Amyloid Cardiomyopathy-Current and Future Therapies. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Impact of tafamidis on myocardial strain in transthyretin amyloid cardiomyopathy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Evolution and prognostic value of left ventricular deformation and myocardial work parameters in Transthyretin Amyloid Cardiomyopathy. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Temporal Trends of Wild-Type Transthyretin Amyloid Cardiomyopathy in the Transthyretin Amyloidosis Outcomes Survey. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Tafamidis: A Review in Transthyretin Amyloid Cardiomyopathy. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Incidence and Predictors of Ventricular Arrhythmias in Transthyretin Amyloid Cardiomyopathy. [2023]