Safety, Efficacy, and Pharmacokinetics of Tafamidis in Patients With Transthyretin-mediated Amyloidosis Post Orthotopic Heart Transplantation

Running, not enrolling · Phase 4

Conditions studied: Transthyretin Cardiac Amyloidosis

In brief

Transthyretin cardiac amyloidosis (ATTR-CA) is a relentlessly progressive disease that can progress to end stage heart failure, at which point recently approved transthyretin production silencing or structure stabilizing therapies provide no clinical benefit. For well-selected individuals, heart transplantation is an excellent therapeutic option to improve survival. Historically, concomitant liver transplantation has been used to halt the progression of non-cardiac transthyretin amyloidosis (ATTR) manifestations, especially for individuals with TTR genotypes associated with significant neuropathy. However, despite this, patients continue to experience progressive non-cardiac manifestations, particularly gastrointestinal and neuropathic, which can have a substantial influence on post-heart transplantation morbidity. Concomitant liver transplantation is also associated with substantial morbidity and its future therapeutic role is questionable with recently established therapies for ATTR. Therefore, there is a clear unmet need to determine the utility and safety of ATTR targeted therapies for patients with recent heart transplantation for end-stage ATTR-CA. The central hypothesis of this proposal is that in patients who have received a heart transplantation for end-stage ATTR-CA, tafamidis therapy will be efficacious and well-tolerated. We aim to determine the safety and efficacy of tafamidis in stable patients who have undergone heart or combined heart/liver transplantation for ATTR (wild-type or variant) cardiac amyloidosis. The proposed study will be a single-arm intervention clinical trial with tafamidis. Because of the efficacy of tafamidis for both variant ATTR-CA and wild-type ATTR-CA, there is no clinical equipoise for an inactive-comparator placebo arm. The primary endpoint of this study will be serial change in plasma transthyretin (TTR) levels from baseline to 12 months at 3-month intervals. The secondary endpoints of this study will include serial changes in neuropathy assessments, modified body mass indices, incident transplant-specific adverse events, and pharmacokinetics of tafamidis. Observations from this study will establish the role of tafamidis use for the management of ATTR in patients after transplantation for end-stage ATTR-CA.

Key facts

Study ID: NCT05489523
Run by: University of Texas Southwestern Medical Center
People needed: 25
Starts: 2023-05-01
Expected to finish: 2027-05-31
Last updated by the study team: 2026-06-04

Who can join

Age: 18 and older, up to 90. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Has received orthotopic heart transplantation for end-stage ATTRv or ATTRwt ≥12 months prior to screening. Concomitant hepatic and renal transplantation with adequate allograft function are included.
Has a stable immunosuppressive regimen and ≤ 10 mg of prednisone (or equivalent) at time of enrollment.
Has a Karnofsky performance status ≥ 70%

You may not qualify if…

Has previously received inotersen within the past 180 days, patisiran within the past 90 days, tafamidis within the past 14 days, or diflunisal in the past 14 days.
Participating in a clinical trial for ATTR targeted therapies.
Has an estimated glomerular filtration rate (eGFR) ≤ 15 ml/min/1.73 m2
Has known leptomeningeal or AL amyloidosis
Has active post-transplant lymphoproliferative disease
Excluding non-melanomatous skin cancers, has an active malignancy.
Has active infection with hepatitis B, hepatitis C, human immunodeficiency virus, or cytomegalovirus (CMV). For CMV, donor/ recipient exposure status and prior treated CMV disease on stable doses of antiviral therapies are not excluded.
Has cardiac allograft dysfunction defined by left ventricular ejection fraction (LVEF) <50% by echocardiogram within the past 3 months
Has been treated for acute cellular or antibody mediated rejection in the past 3 months
Has criteria to meet International Society for Heart and Lung Transplantation standardized nomenclature for severe coronary allograft vasculopathy ("ISHLT CAV3")

Where it is running

Cedars-Sinai — Beverly Hills, California, United States
Columbia University Medical Center — New York, New York, United States
Cleveland Clinic — Cleveland, Ohio, United States
UT Southwestern Medical Center — Dallas, Texas, United States

Full record on ClinicalTrials.gov

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