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

NCT05489523 | Recruiting Phase 4 FDA Drug

• 1 other identifier: STU-2022-0583
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Transthyretin Cardiac Amyloidosis

Keywords

heart transplantation; transthyretin amyloidosis; ATTR; tafamidis

Outcome Measures

Primary Outcomes (1)

• Serial change from baseline in plasma TTR levels at 12 months

  Serial change from baseline in plasma Time in Therapeutic Range (TTR) levels at 12 months is measured at 3 month intervals. TTR tetramer stability is measured using an immunoturbidimetric assay. Increase in plasma TTR levels indicate TTR tetramer stability.

  Baseline, 3, 6, 9, and 12 months

Secondary Outcomes (5)

• Serial change from baseline in Norfolk QoL-DN at 12 months

  Baseline, 3, 6, 9, and 12 months

• Serial change from baseline in Composite Autonomic Symptom Score (COMPASS-31) at12 months

  Baseline, 3, 6, 9, and 12 months

• Number of transplant-specific adverse events

  12 months

• Number of hepatic or renal transplant-specific adverse events

  12 months

• Steady-state plasma concentration of tafamidis in patients undergone HT for end stage ATTR-CA

  Baseline, 3, 6, 9, and 12 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Tafamidis 61 mg

Drug: Tafamidis 61 MG

Interventions

Tafamidis 61 MG DRUG

Tafamidis 61 mg by mouth daily for 12 months

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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")

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (4)

Cedars-Sinai

Beverly Hills, California, 90211, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Amyloidosis, Hereditary, Transthyretin-Related

Interventions

tafamidis

Study Officials

• Justin Grodin, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• Jan Griffin, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amir Mehdizadeh

CONTACT

214-648-7507; Amir.Mehdizadeh@utsouthwestern.edu

Katalin Martits-Chalangari

CONTACT

214-648-2723; Katalin.Martits-Chalangari@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 1, 2022
• First Posted: August 5, 2022
• Study Start: May 1, 2023
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)