48 Clinical Trials for Various Conditions
The MaesTTRo study aims to enroll a global cohort of patients with transthyretin (ATTR) amyloidosis to longitudinally observe the natural course of the disease and describe real-world treatment patterns and outcomes. In addition, information on the effectiveness of ATTR amyloidosis treatments, including eplontersen, which is a ligand-conjugated antisense oligonucleotide gene silencing treatment targeting activity against both the mutant and wild-type TTR protein, will be collected.
The overall aim of this observational study is to generate real-world evidence on the pre- and post-diagnosis disease journeys, including baseline characteristics, treatment patterns and selected clinical, economic, and humanistic outcomes (for example Health Related Quality of Life (HRQoL), Neuropathy impairment score, activities of daily living (ADL) assessments) in patients with ATTR amyloidosis, and to better understand how the disease is presented.
The study design is a prospective registry including asymptomatic and symptomatic patients who carry a pathogenic TTR mutation. The study will enroll patients who meet the inclusion criteria and none of the exclusion criteria until 1000 patients are enrolled, at which point in time the study investigators will evaluate whether further patient accrual is meaningful.
The primary objective of this study is to evaluate the diagnostic performance of an algorithm in identifying patients with ATTR amyloidosis.
The purpose of this study is to: * Describe epidemiological and clinical characteristics, natural history and real-world clinical management of ATTR amyloidosis patients * Characterize the safety and effectiveness of patisiran and vutrisiran as part of routine clinical practice in the real-world clinical setting * Describe disease emergence/progression in pre-symptomatic carriers of a known disease-causing transthyretin (TTR) variant
The purpose of this study is to evaluate the efficacy and safety of patisiran in participants with ATTR amyloidosis with cardiomyopathy.
A Phase 1, open-label study of intravenous (IV) PRX004 as a single agent in subjects with hereditary amyloid transthyretin (hATTR) amyloidosis. The study will consist of 3 phases and will enroll up to a total of 36 subjects. A 3+3 dose escalation component to determine the safety, tolerability, PK, PD, and MTD. An expansion component in anticipated PRX004 RP2D cohorts selected from the Dose Escalation Phase. An extended dosing component for eligible subjects from the Dose Escalation or Expansion phases.
This single-practice prospective cohort study aims to enhance the diagnosis of cardiac amyloidosis in high-risk patients undergoing standard cardiac device implantation. By analyzing chest wall fat tissue, which is usually discarded, we aim to determine the diagnostic yield of such biopsies for amyloidosis and to develop a predictive screening model based on clinical, lab, and imaging data. The study, running from December 2023 to December 2024, expects to enroll 100 patients and may provide a new, non-invasive diagnostic avenue for this condition.
Primary objective: To identify older adults with transthyretin cardiac amyloidosis (ATTR-CA) early in the course of the illness, at a time when disease modifying therapies are most effective. The specific aims of this epidemiologic investigation include: 1. To identify subjects with previous lumbar spinal stenosis (LSS) Surgery who have evidence of transthyretin (TTR) amyloid deposits in spinal specimens and could be at risk for ATTR cardiac amyloidosis. 2. To evaluate for ATTR-CA among those with localized TTR in the spinal tissue. The study will also explore the following: 1. The prevalence of amyloid in lumbar spinal stenosis specimens by Congo Red staining. 2. The prevalence of TTR deposits among subjects with amyloid as determined by mass spectrometry. 3. Evaluation of a novel artificial intelligence technique for that can identify amyloid histologically with standard H\&E staining. 4. Difference in ATTR-CA prevalence between subjects with TTR and indeterminate amyloid deposits in subject's spine by myocardial uptake of technetium pyrophosphate scan (Tc99-PYP).
The objective of the study is to assess the long-term safety of patisiran in patients with ATTR amyloidosis with cardiomyopathy as assessed by a review of adverse events (AEs).
This is an open-label, multi-center pivotal Phase 3 study to visually and quantitatively assess PET images obtained after single application of 300 MBq \[18F\]florbetaben and PET scanning of patients with suspected cardiac amyloidosis.
To evaluate the efficacy and safety of patisiran in patients with wtATTR amyloidosis and symptomatic polyneuropathy by evaluating the effect on neurologic impairment and quality of life.
The purpose of this study is to obtain safety, efficacy, and pharmacodynamic data on the use of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy who continued on extended use of vutrisiran, or switched from patisiran.
This study will investigate 99mTc-p5+14, an amyloid-reactive synthetic peptide, p5+14, radiolabeled with technetium-99m, as a radiotracer for detecting paamyloid deposits in patients with AL or ATTR-associated systemic amyloidosis, notably with cardiac involvement.
The purpose of this study is to determine whether Tolcapone crosses from the blood stream into the fluid around the brain and stabilizes the protein that makes leptomeningeal amyloid. Tolcapone is a commercially available generic drug that treats Parkinson's disease. The Investigator plans to evaluate Tolcapone as a treatment for ATTR (Transthyretin Amyloidosis), a rare genetic disease often causing death within 5-15 years after diagnosis. ATTR is characterized by deposition of misfolded protein known as amyloid, in one or more organ systems (including the peripheral and autonomic nervous systems, the heart, the brain and the eyes). The age at which symptoms begin to develop varies widely ranging between 20 to 70 years old. ATTR is progressive, and some variants can have a fatal outcome within a few years of presentation. Treatment options include supportive and symptomatic care that may slow or stop progressive decline in functional state but do not alter the pathological process. Liver transplant can be performed in selected patients but is limited by organ supply, requires lifelong immunosuppression, and may be complicated by progressive heart and nerve amyloid deposition. Importantly, liver transplant does not alter the natural course of central nervous system amyloid disease. To date, no treatment for ATTR penetrates the CNS. At present there is no FDA approved treatment for ATTR amyloidosis in the US. In Europe, Tafamidis has been approved for treatment of stage 1 ATTR-polyneuropathy since 2012. Tafamidis and Tolcapone bind to the thyroxine binding site of TTR (with different drug-transthyretin interactions) and in so doing stabilizes the tetrameric form of TTR, preventing dissociation and amyloid fibril formation The preclinical and clinical data from a variety of experimental systems support the therapeutic activity of TOLCAPONE in TTR mediated disease.
To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.
See updated study design under NCT04882735. Phase 3 efficacy and safety of AG10 compared with placebo in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)
This study will evaluate the efficacy and safety of vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) compared to placebo in patients with ATTR amyloidosis with cardiomyopathy.
Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein. Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and premature death. Fortunately, new therapies that stabilize TTR improve morbidity and mortality in hATTR-CA, especially when prescribed early in the disease. However, hATTR-CA is often diagnosed at an advanced stage and conventional diagnostic tools lack diagnostic specificity to detect early disease. The overall objectives of this study are to determine the presence of subclinical hATTR-CA and to identify biomarkers that indicate amyloid progression in V122I TTR carriers. The central hypothesis of this proposal is that hATTR-CA has a long latency period that will be detected through subclinical amyloidosis imaging and biomarker phenotyping. The central hypothesis will be tested by pursuing 2 specific aims: Aim 1) determine the association of V122I TTR carrier status with CMRI evidence of amyloid infiltration; Sub-aim 1) determine the association of V122I TTR carrier status with cardiac reserve; Aim 2) determine the association between amyloid-specific biomarkers and V122I TTR carrier status; and Sub-aim 2) determine the association of amyloid-specific biomarkers with imaging-based parameters and evaluate their diagnostic utility for identifying subclinical hATTR-CA. In Aim 1, CMRI will be used to compare metrics associated with cardiac amyloid infiltration between a cohort of V122I TTR carriers without HF formed by cascade genetic testing and age-, sex-, and race-matched non-carrier controls. For Sub-Aim 1, a sub-sample of carriers and non-carrier controls enrolled in Aim 1 will undergo novel exercise CMRI to measure and compare cardiac systolic and diastolic reserve. Aim 2 involves measuring and comparing amyloid-specific biomarkers in V122I TTR carriers without HF with samples matched non-carriers (both from Aim 1) and individuals with symptomatic V122I hATTR-CA from our clinical sites. These biomarkers detect and quantify different processes of TTR amyloidogenesis and include circulating TTR, retinol binding protein 4, TTR kinetic stability, and misfolded TTR oligomers. Sub-aim 2 will establish the role of these biomarkers to detect imaging evidence of subclinical hATTR-CA disease.
The primary objective of this study is to access the efficacy of ALXN2220 in the treatment of adult participants with ATTR-CM by evaluating the difference between the ALXN2220 and placebo groups as assessed by the total occurrences of all-cause mortality (ACM) and cardiovascular (CV) clinical events.
This study is designed to assess the repeatability of organ-specific quantitation of radiotracer uptake following Positron Emission Tomography/Computed Tomography (PET/CT) imaging of AT- 01 in subjects with amyloid light chain (AL) or amyloid transthyretin (ATTR) systemic amyloidosis.
This is a single center Phase 1 study is to evaluate the biodistribution of radiolabeled AT-03 in patients with systemic amyloidosis.
Open-label Safety and Efficacy Evaluation of Fx-1006a in Patients with V122i Or Wild-type Transthyretin (ttr) Amyloid Cardiomyopathy. Patients who successfully complete Fx1B-201 will report to the clinical unit on Day 0 to sign the informed consent form and determine eligibility for Protocol Fx1B-303. In addition, on Day 0, patients will have their entrance criteria reviewed, and medical histories and demographic characteristics obtained. The physical examination (including weight and vital signs) and the relevant end of study clinical laboratory tests (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, gamma glutamyl transferase, creatinine, total bilirubin, international normalized ratio, troponin I, troponin T, and amino-terminal B-type natriuretic peptide) from Protocol Fx1B-201 will be used for Protocol Fx1B-303. If more than 30 days has elapsed between the final study visit of Protocol Fx1B-201 and Day 0 of Protocol Fx1B-303, an abbreviated physical examination (including weight and vital signs) and clinical laboratory assessments must be performed on Day 0. Eligible patients will begin once-daily dosing with 20 mg Fx-1006A at home on Day 1 (i.e., first dose) and will return to the clinical unit for study visits every 6 months. Adverse events (AEs) and concomitant medication use will be collected at each 6-month visit to the clinical unit. Blood draws for clinical safety laboratory tests and abbreviated physical examinations (including weight and vital signs) will also be performed at each 6-month clinic visit. ECGs will be performed every 12 months on an annual basis. A telephone call will be made at 3-month intervals between clinic visits to assess safety and use of concomitant medications. For the evaluation of efficacy, the Patient Global Assessment, NYHA classification, KCCQ, 6-minute walk test, and efficacy-related clinical laboratory tests (serum levels of troponin T, troponin I, and NT-pro-BNP) will be determined every 6 months. In addition, echocardiograms will be performed every 12 months on an annual basis. An end of study visit including all safety and efficacy assessments will occur upon patient completion of the study, premature withdrawal (for any reason), or in the event of program discontinuation by the Sponsor.
The purpose of this study is to evaluate the safety and tolerability of extended dosing with eplontersen in participants with ATTR-CM.
To evaluate the efficacy of eplontersen compared to placebo in participants with ATTR-CM receiving available standard of care (SoC). For more information, please visit https://www.cardio-ttransform.com.
This study will examine the clinical effectiveness of Tafamidis in patients with Mixed Phenotype Transthyretin Amyloidosis using data that already exist in patients' medical records
This study will test a medicine, NNC6019-0001, for people who have a heart disease due to TTR amyloidosis. It will look at how safe this medicine is in the long term and if it can reduce symptoms of a heart disease due to TTR amyloidosis, such as heart failure. It is an extension to a study called "A research study to look at how a new medicine called NNC6019-0001 works and how safe it is for people who have a heart disease due to TTR amyloidosis". Only participants who have completed that study will be invited for this new study. Participants will get NNC6019-0001, regardless of whether they got placebo or NNC6019-0001 in the first study. The study will last for up to 157 weeks (36 months/3 years).
The purpose of this study is to examine the changes in amyloid myocardial burden in a subset of the population participating in the ION682884-CS2 (NCT04136171) study, up to 150 participants, after treatment with eplontersen or placebo based on scintigraphy scans performed at Week 140 using the Perugini grade score method.
The main purpose of this study is to measure the amyloid burden, defined as extracellular volume (ECV) assessed by Magnetic Resonance Imaging (MRI) over time in a subset of up to 150 participants enrolled in ION-682884-CS2 (NCT04136171).
This study is testing a potential new medicine, NNC6019-0001, for people who have a heart disease due to TTR amyloidosis.The study will look at if this medicine can reduce the symptoms of a heart disease due to TTR amyloidosis, such as heart failure. Participants will either get NNC6019-0001 (apotential new medicine) or placebo (a medicine which has no effect on the body). Which treatment participants get is decided by chance. The chance of getting NNC6019-0001 is two times higher than getting placebo. NNC6019-0001 is not yet approved in any country or region in the world. It is a new medicine that doctors cannot prescribe yet. Participants will get an infusion of the study medicine 13 times, once every 4 weeks. The study will last for about 64 weeks after the first dose of medicine. Participants cannot participate in this study if they have a heart disease other than a heart disease due to TTR amyloidosis.