Transthyretin Cardiac AmyloidosisPhase 4NCT05489523
Safety, Efficacy, and Pharmacokinetics of Tafamidis in Patients With Transthyretin-mediated Amyloidosis Post Orthotopic Heart Transplantation
A Phase 4 study testing Tafamidis 61 MG in people with Transthyretin Cardiac Amyloidosis, run by University of Texas Southwestern Medical Center at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Transthyretin Cardiac Amyloidosis
- What is being tested?
- Tafamidis 61 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 May 2023to 31 May 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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.
Show all 10Show fewer
- 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")
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Cedars-Sinai
Beverly Hills, California, 90211
Cleveland Clinic
Cleveland, Ohio, 44195
UT Southwestern Medical Center
Dallas, Texas, 75390
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: An Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Tafamidis in Patients With Transthyretin-mediated Amyloidosis Post Orthotopic Heart Transplantation
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.
Read the detailed description
- Primary Aim
To determine the safety and efficacy of tafamidis in patients who have undergone heart or combined heart/liver transplantation for ATTR (wild-type or variant) cardiac amyloidosis.
Primary Hypothesis. Initiation of the TTR stabilizer, tafamidis, post heart or heart/liver transplant for ATTR cardiac amyloidosis, (wild-type or variant disease) will be associated with an increase in plasma transthyretin levels during 12 months of therapy.
- Secondary Aims
- To determine the impact of tafamidis on serial questionnaire assessments that quantitate and determine the severity and clinical implications of motor, sensory, and autonomic neurologic impairment in participants over 12 months with cardiac transplantation.
- To determine the impact of tafamidis on serial questionnaire assessment of activity and social participation limitation, dysautonomia and nutritional status in participants over 12 months with cardiac transplantation.
- To determine the impact of tafamidis on transplantation-related adverse events in participants over 12 months with cardiac transplantation.
- To establish the pharmacokinetics of tafamidis in participants with cardiac transplantation over 12 months.
- Study Type / Design
The proposed study will be a single-arm, intervention clinical trial. Because of the observed efficacy of tafamidis and other therapies for both ATTRv and ATTRwt, there is no clinical equipoise for an inactive-comparator placebo arm.
- Expected Outcomes
Upon completion of this clinical trial, it is our expectation that we will establish the efficacy and safety of tafamidis in patients with who have undergone heart transplantation for ATTR-CA. Further, we expect to have shown that tafamidis will have predictable pharmacokinetics and will lead to improvement in polyneuropathy questionnaire scores and mBMI. Such findings would be important, because they would justify the use of tafamidis to halt ATTR progression in patients who have undergone heart transplantation for advanced ATTR-CA.
Specifically, we will expect the following:
- Tafamidis will be safe and well tolerated in the post heart transplant population, providing data to support its use as a therapeutic agent to halt the progression of extra cardiac manifestations of TTR amyloidosis post HT for end stage ATTR-CA.
- TTR levels will increase from baseline at the 3-month visit and remain stable throughout the remainder of the study period. This increase in serum TTR will be comparable to that seen in the ATTR-ACT trial, reflective of stabilization of TTR and treatment efficacy in this patient population.
- Serial assessment of Norfolk-QoL-DN, COMPASS-31 and R-ODS questionnaires will demonstrate stable disease at 12 months as measured by autonomic symptoms and quality of life.
- There will be no increase, from baseline, in incidence of treated acute cellular rejection, antibody mediated rejection, active CMV infection, coronary allograft vasculopathy or post-transplant lymphoproliferative disorder as a result of concurrent TTR stabilizing therapy with tafamidis.
- Plasma pharmacokinetics of tafamidis free acid in the post HT population will be similar to those observed in previous studies of healthy volunteers.
- Conditions
- Transthyretin Cardiac Amyloidosis
- Being tested
- Tafamidis 61 MG
- Keywords
- heart transplantation, transthyretin amyloidosis, ATTR, tafamidis
- Medical subject headings
- Amyloidosis, Hereditary, Transthyretin-Related
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tafamidis 61 MGDrug
Tafamidis 61 mg by mouth daily for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Tafamidis 61 mg Receives: Drug: Tafamidis 61 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 3, 6, 9, and 12 months
Secondary outcomes (5)
Serial change from baseline in Norfolk QoL-DN at 12 months
Serial change from baseline in Norfolk Quality of Life Diabetic Neuropathy (QoL-DN) at 12 months is measured at 3 month intervals. The Norfolk-QoL-DN total score differentiates between healthy subjects and individuals with ATTRv polyneuropathy as well as different stages of Transthyretin amyloidosis (ATTR) polyneuropathy. The total score has a range of -4 to 136, with a higher score indicating worse disease symptoms. There are five different domains assessed within an overall quality of life score: symptoms, large fiber, small fiber, activities of daily living and autonomic dysfunction.
Measured: Baseline, 3, 6, 9, and 12 months
Serial change from baseline in Composite Autonomic Symptom Score (COMPASS-31) at12 months
Serial change from baseline in Composite Autonomic Symptom Score (COMPASS-31) at12 months is measured at 3 month intervals. COMPASS-31 is a 31-question participant-reported assessment that measures autonomic symptoms across 6 weighted domains on a 100-point scale: orthostatic intolerance (40 points), vasomotor (5 points), secretomotor (15 points), gastrointestinal (25 points), bladder (10 points), and pupillomotor (15 points). A higher score indicates worse autonomic dysfunction.
Measured: Baseline, 3, 6, 9, and 12 months
Number of transplant-specific adverse events
Transplant-specific Adverse events will be determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Measured: 12 months
Number of hepatic or renal transplant-specific adverse events
Hepatic or renal transplant-specific adverse events will be determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Measured: 12 months
Steady-state plasma concentration of tafamidis in patients undergone HT for end stage ATTR-CA
Steady-state plasma pharmacokinetic (PK) parameters will calculated based on plasma concentration of tafamidis in patients who have undergone HT for end stage ATTR-CA.
Measured: Baseline, 3, 6, 9, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2022
- Study start1 May 2023
- Primary completion31 May 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transthyretin Cardiac AmyloidosisStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Justin Grodin, University of Texas Southwestern Medical Center
- Investigators
- Justin Grodin, MD, Principal investigator, University of Texas Southwestern Medical CenterJan Griffin, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05489523
- Sponsor's protocol ID
- STU-2022-0583
- Status last verified
- May 2026
- First submitted
- 1 Aug 2022
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Tafamidis in Patients With Transthyretin-mediated Amyloidosis Post Orthotopic Heart Transplantation
- ClinicalTrials.gov ID
- NCT05489523
- Acronym / sponsor ID
- STU-2022-0583
- Conditions
- Transthyretin Cardiac Amyloidosis
- Keywords
- heart transplantation, transthyretin amyloidosis, ATTR, tafamidis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 1 May 2023 (actual)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 5 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- Primary Aim
To determine the safety and efficacy of tafamidis in patients who have undergone heart or combined heart/liver transplantation for ATTR (wild-type or variant) cardiac amyloidosis.
Primary Hypothesis. Initiation of the TTR stabilizer, tafamidis, post heart or heart/liver transplant for ATTR cardiac amyloidosis, (wild-type or variant disease) will be associated with an increase in plasma transthyretin levels during 12 months of therapy.
- Secondary Aims
- To determine the impact of tafamidis on serial questionnaire assessments that quantitate and determine the severity and clinical implications of motor, sensory, and autonomic neurologic impairment in participants over 12 months with cardiac transplantation.
- To determine the impact of tafamidis on serial questionnaire assessment of activity and social participation limitation, dysautonomia and nutritional status in participants over 12 months with cardiac transplantation.
- To determine the impact of tafamidis on transplantation-related adverse events in participants over 12 months with cardiac transplantation.
- To establish the pharmacokinetics of tafamidis in participants with cardiac transplantation over 12 months.
- Study Type / Design
The proposed study will be a single-arm, intervention clinical trial. Because of the observed efficacy of tafamidis and other therapies for both ATTRv and ATTRwt, there is no clinical equipoise for an inactive-comparator placebo arm.
- Expected Outcomes
Upon completion of this clinical trial, it is our expectation that we will establish the efficacy and safety of tafamidis in patients with who have undergone heart transplantation for ATTR-CA. Further, we expect to have shown that tafamidis will have predictable pharmacokinetics and will lead to improvement in polyneuropathy questionnaire scores and mBMI. Such findings would be important, because they would justify the use of tafamidis to halt ATTR progression in patients who have undergone heart transplantation for advanced ATTR-CA.
Specifically, we will expect the following:
- Tafamidis will be safe and well tolerated in the post heart transplant population, providing data to support its use as a therapeutic agent to halt the progression of extra cardiac manifestations of TTR amyloidosis post HT for end stage ATTR-CA.
- TTR levels will increase from baseline at the 3-month visit and remain stable throughout the remainder of the study period. This increase in serum TTR will be comparable to that seen in the ATTR-ACT trial, reflective of stabilization of TTR and treatment efficacy in this patient population.
- Serial assessment of Norfolk-QoL-DN, COMPASS-31 and R-ODS questionnaires will demonstrate stable disease at 12 months as measured by autonomic symptoms and quality of life.
- There will be no increase, from baseline, in incidence of treated acute cellular rejection, antibody mediated rejection, active CMV infection, coronary allograft vasculopathy or post-transplant lymphoproliferative disorder as a result of concurrent TTR stabilizing therapy with tafamidis.
- Plasma pharmacokinetics of tafamidis free acid in the post HT population will be similar to those observed in previous studies of healthy volunteers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Tafamidis 61 MGTafamidis 61 mg |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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%
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tafamidis 61 MGTafamidis 61 mg by mouth daily for 12 months | Drug | Treatment Arm |
Primary outcome
Serial change from baseline in plasma TTR levels at 12 months
Time frame: Baseline, 3, 6, 9, and 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.
5 secondary outcomes
Serial change from baseline in Norfolk QoL-DN at 12 months
Time frame: Baseline, 3, 6, 9, and 12 months
Serial change from baseline in Composite Autonomic Symptom Score (COMPASS-31) at12 months
Time frame: Baseline, 3, 6, 9, and 12 months
Number of transplant-specific adverse events
Time frame: 12 months
Number of hepatic or renal transplant-specific adverse events
Time frame: 12 months
Steady-state plasma concentration of tafamidis in patients undergone HT for end stage ATTR-CA
Time frame: Baseline, 3, 6, 9, and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Justin Grodin, MD principal investigator
University of Texas Southwestern Medical Center
Jan Griffin, MD principal investigator
Medical University of South Carolina
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tafamidis 61 MG in people with Transthyretin Cardiac Amyloidosis, run by University of Texas Southwestern Medical Center at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serial change from baseline in plasma TTR levels at 12 months (time frame: Baseline, 3, 6, 9, and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.