Tafamidis for Transthyretin Amyloid Cardiomyopathy

Recruiting at 3 trial locations

Overseen By Katalin Martits-Chalangari

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Tafamidis

Must not be taking: Inotersen, Patisiran, Diflunisal

Disqualifiers: Low eGFR, Active malignancy, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 months

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness and safety of tafamidis (also known as Vyndamax or Vyndaqel) for individuals who have undergone a heart transplant due to transthyretin amyloid cardiomyopathy (ATTR-CA), a condition that can cause serious heart issues. The researchers aim to determine if tafamidis can halt disease progression in these patients. Eligible participants must have had a heart transplant for at least a year due to ATTR-CA and maintain a stable medication routine. Participants cannot have recently used certain other ATTR treatments or have specific health conditions, such as severe kidney issues. The trial will track changes in specific health indicators over time. As a Phase 4 trial, this research seeks to understand how tafamidis, already FDA-approved and proven effective, benefits a broader patient population.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain medications like tafamidis, inotersen, patisiran, or diflunisal recently. It's best to discuss your current medications with the trial team.

What is the safety track record for tafamidis?

Research has shown that tafamidis is generally safe for people. In studies involving patients with transthyretin cardiac amyloidosis (ATTR-CM), those taking tafamidis experienced side effects similar to those taking a placebo (a harmless pill used for comparison). Longer-term research indicates that higher doses of tafamidis do not result in more side effects. Additionally, tafamidis is approved for a related condition, suggesting it is well-tolerated. Overall, tafamidis has a strong safety record for treating conditions like the one under study in this trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard of care for transthyretin amyloid cardiomyopathy, which often includes treatments like diuretics and heart failure medications, Tafamidis works by stabilizing the transthyretin protein, preventing it from misfolding and forming harmful amyloid deposits. This unique mechanism of action directly targets the root cause of the disease, rather than just managing symptoms. Researchers are excited about Tafamidis because it has the potential to slow disease progression and improve quality of life for patients, offering hope for a condition that currently has limited treatment options.

What is the effectiveness track record for tafamidis in treating transthyretin amyloid cardiomyopathy?

Research shows that tafamidis effectively treats transthyretin amyloid cardiomyopathy (ATTR-CM). Studies have found that it helps people live longer and reduces hospital visits for heart issues. Specifically, the ATTR-ACT trial demonstrated that participants taking tafamidis had better outcomes than those on a placebo, which contains no active medicine. Long-term use of tafamidis also appears to slow disease progression. These findings suggest that tafamidis can be a helpful treatment for this condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Jan Griffin, MD

Principal Investigator

Medical University of South Carolina

Justin Grodin, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for patients who've had a heart transplant at least 12 months ago due to end-stage Transthyretin Amyloid Cardiomyopathy (ATTR-CA). They should be relatively healthy otherwise, with stable organ function and not taking high doses of immune-suppressing drugs. People with active cancers (except certain skin cancers), infections like hepatitis or HIV, severe heart issues post-transplant, recent rejection treatments, very poor kidney function, or other types of amyloidosis can't join.

Inclusion Criteria

I am on a stable medication regimen for my immune system, taking 10 mg or less of prednisone.

I am mostly able to care for myself and carry out daily activities.

I had a heart transplant over a year ago due to advanced ATTR.

Exclusion Criteria

You are currently taking part in a clinical trial for treatments that target ATTR.

I have been treated for organ rejection in the last 3 months.

My heart's pumping ability is reduced (LVEF <50%).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tafamidis therapy post heart or heart/liver transplantation for 12 months

12 months

Visits at baseline, 3, 6, 9, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Tafamidis

Trial Overview The study tests Tafamidis 61 MG's safety and effectiveness in patients after a heart transplant due to ATTR-CA. It's a single-arm trial where all participants receive the drug—no placebo group—focusing on how it affects protein levels related to ATTR-CA over one year and its impact on nerve health, body mass index changes, specific side effects related to the transplant, and how the body processes the drug.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

Tafamidis 61 mg

Tafamidis is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Vyndaqel for:

• Transthyretin amyloid polyneuropathy (ATTR-PN)
• Transthyretin amyloid cardiomyopathy (ATTR-CM)

Approved in United States as Vyndamax for:

• Transthyretin amyloid cardiomyopathy (ATTR-CM)

Approved in Japan as Vyndaqel for:

• Transthyretin amyloid polyneuropathy (ATTR-PN)
• Transthyretin amyloid cardiomyopathy (ATTR-CM)

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Tafamidis meglumine is a first-in-class drug that effectively stabilizes the transthyretin (TTR) protein, preventing the formation of harmful amyloid aggregates associated with transthyretin familial amyloid polyneuropathy (TTR-FAP).

Clinical trials have shown that tafamidis slows disease progression and improves nerve function in patients with TTR-FAP, leading to better overall health outcomes, and it has received marketing authorization in Europe, with ongoing review in the U.S. for the same condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafamidis for transthyretin amyloidosis. de Lartigue, J.[2017]

A single 400 mg dose of tafamidis does not prolong the QTc interval in healthy volunteers, indicating it is safe in terms of cardiac effects.

The study, involving 42 participants, showed that tafamidis was well-tolerated with no serious adverse events, supporting its safety profile for potential use in treating TTR cardiomyopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of tafamidis on the QTc interval in healthy subjects. Klamerus, KJ., Watsky, E., Moller, R., et al.[2018]

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]

Tafamidis is effective in treating both variant (ATTRv) and wild-type (ATTRwt) transthyretin amyloid cardiomyopathy, showing similar reductions in mortality and functional decline for both types, based on a study of 441 patients.

Patients with ATTRwt had less advanced disease and a slower progression compared to those with ATTRv, but tafamidis provided comparable benefits in improving walking distance and quality of life measures for both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Tafamidis in Patients With Hereditary and Wild-Type Transthyretin Amyloid Cardiomyopathy: Further Analyses From ATTR-ACT. Rapezzi, C., Elliott, P., Damy, T., et al.[2021]

Tafamidis has been shown to significantly reduce all-cause mortality and cardiovascular hospitalizations in patients with transthyretin cardiac amyloidosis, highlighting its efficacy as a treatment option.

The Japanese Ministry of Health has approved tafamidis for treating cardiomyopathy caused by both wild-type and mutated transthyretin-derived amyloidoses, indicating its recognized importance in managing this underdiagnosed and serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Statement on the Appropriate Administration of Tafamidis in Patients With Transthyretin Cardiac Amyloidosis. Endo, J., Sano, M., Izumiya, Y., et al.[2020]

Tafamidis is the first approved medication for transthyretin amyloid cardiomyopathy (ATTR-CM), significantly reducing mortality and cardiovascular-related hospitalizations compared to placebo, based on clinical studies.

The drug works by stabilizing transthyretin, preventing its dissociation into harmful monomers, and has a favorable safety profile with fewer adverse events than placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafamidis: A First-in-Class Transthyretin Stabilizer for Transthyretin Amyloid Cardiomyopathy. Park, J., Egolum, U., Parker, S., et al.[2020]

Tafamidis significantly reduces all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), with a median follow-up of 51 months from the ATTR-ACT trial and its long-term extension study.

The 80 mg dose of tafamidis showed a greater survival benefit compared to the 20 mg dose, while both doses had a safety profile comparable to placebo, suggesting that 80 mg is the optimal dose for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. Damy, T., Garcia-Pavia, P., Hanna, M., et al.[2021]

Tafamidis significantly reduces the risk of all-cause mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) by 30% compared to placebo, with estimated median overall survival of 52.64 months for tafamidis versus 35.16 months for placebo.

A gamma distribution model was used to analyze survival data from the ATTR-ACT trial, providing further evidence of tafamidis's efficacy, although these estimates should be interpreted cautiously due to the limitations of the analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrapolation of Survival Benefits in Patients with Transthyretin Amyloid Cardiomyopathy Receiving Tafamidis: Analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial. Li, B., Alvir, J., Stewart, M.[2020]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1875213624003231

Tafamidis meglumine early access program in France Clinical Research. Clinical outcomes for 2788 patients with transthyretin amyloidosis: Tafamidis meglumine early access program in France☆.

2. jacc.org jacc.org/doi/10.1016/j.jaccas.2024.102771

Long-Term Outcomes of Tafamidis Treatment for ... This case series suggests that tafamidis has the potential to sustainably delay progression of ATTR-CM.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05139680?term=VYNDAMAX&rank=3&tab=results

A Study to Examine the Clinical Effectiveness of Tafamidis ... A study to examine the clinical effectiveness of Tafamidis in patients with mixed phenotype hereditary transthyretin amyloidosis.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12046781/

A Multicenter Study of Contemporary Long-Term Tafamidis ... Tafamidis improved survival and decreased cardiovascular hospitalizations in the ATTR-ACT trial. Due to improved recognition and earlier ...

5. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/2811926

Effect of Tafamidis on Cardiac Function in Patients With ... Importance Tafamidis has been shown to improve survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with placebo.

6. vyndamax.pfizerpro.com vyndamax.pfizerpro.com/about-vyndamax/study-design

Study Design | VYNDAMAX® (tafamidis) | Safety Info Approval of VYNDAMAX was based on ATTR-ACT, a phase 3, multicenter, international, randomized, double-blind, placebo-controlled study.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8048553/

Efficacy and safety of tafamidis doses in ... The longer‐term survival data and the lack of dose‐related safety concerns support tafamidis 80 mg as the optimal dose. Clinical Trial Registration: ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01994889

NCT01994889 | Safety and Efficacy of Tafamidis in ... This Phase 3 study will investigate the efficacy, safety and tolerability of an oral daily dose of 20 mg or 80 mg tafamidis meglumine capsules compared to ...

9. jacc.org jacc.org/doi/10.1016/j.jaccao.2024.12.005

A Multicenter Study of Contemporary Long-Term Tafamidis ... In a contemporary cohort of tafamidis-treated patients with ATTR-CM, 39% of patients died over a median of 43 months.

10. vyndamax.pfizerpro.com vyndamax.pfizerpro.com/about-attrcm/disease-impact

About ATTR Cardiac Amyloidosis In studies in patients with ATTR-CM, the frequency of adverse events in patients treated with VYNDAQEL® (tafamidis meglumine) was similar to placebo.