Een studie om meer te leren over de verandering in de bloedspiegels van transthyretine wanneer deelnemers met transthyretine-amyloïdose met cardiomyopathie overschakelen van tafamidis naar acoramidis (ACO-SWITCH)
Een prospectief, single-arm, fase 4-onderzoek om het beloop van het serumtransthyretine (TTR)-gehalte te evalueren met acoramidis bij volwassen patiënten met variant- of wildtype transthyretine-amyloïdose met cardiomyopathie (ATTR-CM) die eerder met tafamidis zijn behandeld
Transthyretin (TTR) is a protein made by the liver that helps transport thyroid hormone and vitamin A in the blood. In some people, this protein breaks down and forms harmful clumps called amyloid. TTR amyloid gets deposited in the heart wall and stops it from pumping blood properly, which may lead to heart failure. The breakage in TTR protein can be age-related (wild-type ATTR-CM), or genetic (variant ATTR-CM).
The study drug, acoramidis, works by attaching itself to the TTR protein, making TTR more stable and less likely to break down and form amyloid (clumps). This helps to slow down the progression of the disease, improve heart function, and increase the TTR levels in the blood. Acoramidis is an approved treatment for wild-type or variant ATTR-CM in Europe and the United States.
Tafamidis is another drug that stabilizes TTR and prevents it from breaking down.
In this study, acoramidis will be studied in participants with ATTR--CM who were previously treated with tafamidis. The main purpose of this study is to assess the change in blood TTR levels after participants are switched from tafamidis to acoramidis. This will be studied to understand if acoramidis causes an increase in blood TTR levels beyond the levels achieved with tafamidis.
For this, the researchers will measure the change in the levels of TTR protein in participants' blood after 6 months of the treatment with acoramidis, or earlier if a participant stops the treatment before reaching that six-month mark.
All participants will continue taking tafamidis during the screening period. In the treatment period of the study, participants will take acoramidis as two tablets twice daily by mouth, for up to 6 months.
At the start of this study, the study doctors will review each participant's medical history and check their overall health. The study doctors will perform electrocardiograms (ECG), and measure blood pressure and heart rate. Researchers will also take blood and urine samples from the participants to measure levels of TTr, NT-proBNP, hs-TnT, hs-CRP, RBP4, eGFR, creatinine, cystatin-C, UACR, and TSH at the start of the study, and at various time points thereafter (during the study) to assess heart, kidney and thyroid function.
There will be a total of 9 study check-ins. Participants will visit the study site twice: at screening and at the end of treatment period. A study nurse will visit the participant's home 6 times, at the start of treatment, Weeks 1, 2, 3 and 4, then again at 3 months. The final check-in will be done by phone.
The study doctors will monitor the health of the participants regularly for any medical problems during follow-up visits. Participants will know the treatment they will receive during the study. Each participant could be in the study for about 8 months.
Studie Overzicht
Toestand
Interventie / Behandeling
Studietype
Inschrijving (Geschat)
Fase
- Fase 4
Contacten en locaties
Studiecontact
- Naam: Bayer Clinical Trials Contact
- Telefoonnummer: 18888422937
- E-mail: clinical-trials-contact@bayer.com
Studie Locaties
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Brussels Capital
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Brussels, Brussels Capital, België, 1070
- Nog niet aan het werven
- Hôpital Erasme/Erasmus Ziekenhuis
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West Flanders
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Bruges, West Flanders, België, 8000
- Nog niet aan het werven
- AZ St-Jan Brugge-Oostende A.V.
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Berlin, Duitsland, 10365
- Ingetrokken
- Sana Klinikum Lichtenberg - Klinik für Innere Medizin II, Schwerpunkt Kardiologie
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Hamburg, Duitsland, 20246
- Ingetrokken
- Universitätsklinikum Hamburg Eppendorf (UKE)-Universitären Herz- und Gefäßzentrum Hamburg, Klinik für Kardiologie
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Baden-Wurttemberg
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Ulm, Baden-Wurttemberg, Duitsland, 89081
- Ingetrokken
- Universitaetsklinikum Ulm | Klinik fuer Innere Medizin II
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Hesse
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Darmstadt, Hesse, Duitsland, 64287
- Nog niet aan het werven
- KVZ Kardiovaskulaeres Zentrum Darmstadt GmbH
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Mecklenburg-Vorpommern
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Greifswald, Mecklenburg-Vorpommern, Duitsland, 17475
- Ingetrokken
- Universitaetsmedizin Greifswald KöR- Klinik und Poliklinik für Innere Medizin B
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North Rhine-Westphalia
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Bonn, North Rhine-Westphalia, Duitsland, 53127
- Ingetrokken
- Universitätsklinikum Bonn - Herzzentrum des Universitätsklinikums Bonn
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Naples, Italië, 80131
- Nog niet aan het werven
- Azienda Ospedaliera Dei Colli_Monaldi - Malattie Rare e Genetiche Cardiovascolari
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Apulia
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Lecce, Apulia, Italië, 73100
- Nog niet aan het werven
- Ospedale Vito Fazzi Lecce_Cardiologia e UTIC
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Emilia-Romagna
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Bologna, Emilia-Romagna, Italië, 40138
- Nog niet aan het werven
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS_Policlinico Sant'Orsola_Cardiologia
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Lombardy
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Bergamo, Lombardy, Italië, 24127
- Werving
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII - Cardiologia 1
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Milan, Lombardy, Italië, 20138
- Werving
- Centro Cardiologico Monzino S.p.A. - Cardiologia Peri-Operatoria e Imaging Cardiovascolare
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Pavia, Lombardy, Italië, 27100
- Nog niet aan het werven
- Fondazione IRCCS Policlinico San Matteo-SC Medicina Generale 2 - Centro Amiloidosi Sistemiche e Malattie ad Alta Complessità
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Tuscany
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Florence, Tuscany, Italië, 50134
- Werving
- Careggi University Hospital_cardio intensive care unit
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Pisa, Tuscany, Italië, 56124
- Werving
- Fondazione Toscana Gabriele Monasterio_Pisa - Cardiologia e Medicina Cardiovascolare
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Siena, Tuscany, Italië, 53100
- Werving
- Azienda Ospedaliera Universitaria Senese - cardiologia
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Veneto
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Padova, Veneto, Italië, 35128
- Werving
- Azienda Ospedale-Università di Padova-UOC Cardiologia
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Oslo, Noorwegen, 0424
- Nog niet aan het werven
- Oslo Universitetssykehus HF, Rikshospitalet
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Lower Austria
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Sankt Pölten, Lower Austria, Oostenrijk, 1210
- Ingetrokken
- Universitätsklinikum St. Pölten - Lilienfeld - Klinische Abteilung für Innere Medizin 3
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State of Vienna
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Vienna, State of Vienna, Oostenrijk, 3500
- Nog niet aan het werven
- Klinik Ottakring - 3. Medizinische Abteilung mit Kardiologie, internistischer Intensivmedizin und Ambulanz
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Vienna, State of Vienna, Oostenrijk, 1090
- Werving
- Medizinische Universität Wien- Universitätsklinik für Innere Medizin II, Klinische Abteilung für Kardiologie
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Vienna, State of Vienna, Oostenrijk, 1100
- Werving
- Klinik Favoriten - 5.Medizinische Abteilung-Kardiologie
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Styria
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Vienna, Styria, Oostenrijk, 1030
- Werving
- Medizinische Universität Graz- Klinische Abteilung für Kardiologie
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Upper Austria
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Braunau am Inn, Upper Austria, Oostenrijk, 5280
- Werving
- Krankenhaus St. Josef Braunau | Innere Medizin I
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Vorarlberg
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Feldkirch, Vorarlberg, Oostenrijk, 6800
- Ingetrokken
- VIVIT - Landeskrankenhaus Feldkirch - Innere Medizin I, Kardiologie, Angiologie, Endokrinologie, Diabetologie, Intensivmedizin
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Participants must be 18 to 90 years of age inclusive, at the time of signing the informed consent.
- Diagnosis of ATTR-CM; disease defining examination, i.e., Single Photon Emission Computed Tomography (SPECT) or SPECT/Computed Tomography (CT) or biopsy, within 24 months prior to Visit 1 (V1).
- Participants must currently be treated with tafamidis and have used tafamidis for at least the previous 3 months prior to V1 and have adhered to tafamidis therapy.
- New York Heart Association (NYHA) class ≤ II at V1.
- Estimate glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m^2 at V1.
- N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) > 300 and ≤ 7000 pg/mL at V1.
Exclusion Criteria:
- Prior liver or heart transplantation or planned within the next 12 months.
- Current or planned use of ventricular assist device.
- Active cancer or other disease that decreases the life expectancy to less than one year.
- Heart failure due to ischemic heart disease.
- Myocardial infarction, cardiovascular (CV) surgery, or unstable angina within the last 90 days prior to V1.
- Confirmed diagnosis of light-chain amyloidosis.
- Dialysis or severe renal impairment as reflected by Urinary Albumin Creatinine Ratio (UACR) > 300 mg/g at V1.
- Major surgery within 90 days prior to V1.
- Recent initiation of Sodium-Glucose-Cotransporter-2 inhibitors (SGLT2i) within 3 months before V1.
- Initiation of treatment with a diuretic or increase in diuretic dose within 3 months before V1.
- Treatment with calcium channel blockers (e.g., verapamil, diltiazem) or digitalis.
- Recent CV hospitalization within 3 months before V1.
- Known hypersensitivity to acoramidis or to any of the excipients.
- A condition that, as judged by the investigator, would preclude compliance with the study protocol, such as a history of substance abuse, alcoholism, or a psychiatric condition.
- Known or suspected liver disorder and bile secretion/flow (cholestasis, also history of it).
- Abnormal liver function tests at V1, defined as ALT (GPT) or AST (GOT) ≥ 3 x ULN or total bilirubin ≥ 3 x ULN at V1.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Acoramidis
Participants will receive acoramidis 712 mg orally BID |
356 mg film-coated tablets. The recommended dose of acoramidis is 712 mg (two tablets, 356 mg) orally, twice daily, corresponding to a total daily dose of 1424 mg.
Andere namen:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Change in serum TTR level from baseline to month 6 or premature discontinuation of treatment
Tijdsspanne: From baseline to month 6 or premature discontinuation of treatment
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TTR = Transthyretin |
From baseline to month 6 or premature discontinuation of treatment
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Aantal deelnemers met TEAE's en ernstige TEAE's
Tijdsspanne: Vanaf de eerste toediening van het onderzoeksgeneesmiddel tot 30 dagen na de laatste dosis van het onderzoeksgeneesmiddel of het einde van de studie, afhankelijk van wat zich het eerst voordoet
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Vanaf de eerste toediening van het onderzoeksgeneesmiddel tot 30 dagen na de laatste dosis van het onderzoeksgeneesmiddel of het einde van de studie, afhankelijk van wat zich het eerst voordoet
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Verandering van baseline naar maand 6 in Creatinine
Tijdsspanne: Van baseline tot maand 6
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Van baseline tot maand 6
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Verandering van baseline tot maand 6 in Cystatine C
Tijdsspanne: Van baseline tot maand 6
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Van baseline tot maand 6
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Change in serum TTR level from baseline to week 1, 2, 3, 4 and at month 3.
Tijdsspanne: At baseline, week 1, 2, 3, 4 and at month 3
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TTR = Transthyretin |
At baseline, week 1, 2, 3, 4 and at month 3
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Change from baseline to month 6 of NT-proBNP
Tijdsspanne: From baseline to month 6
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NT-proBNP = N-terminal pro-B-type Natriuretic Peptide |
From baseline to month 6
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Change from baseline to month 6 of hs-TnT
Tijdsspanne: From baseline to month 6
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hs-TNT = high-sensitivity Troponin T |
From baseline to month 6
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Change from baseline to month 6 of RBP4
Tijdsspanne: From baseline to month 6
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RBP4 = Retinol Binding Protein 4 |
From baseline to month 6
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Signs of cardiac remodeling from baseline to month 6
Tijdsspanne: From baseline to month 6
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These signs will be measured by echocardiogram |
From baseline to month 6
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Change from baseline to month 6 in 6MWD
Tijdsspanne: From baseline to month 6
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The 6-Minute Walk distance (6MWD) measures the total distance that a participant could walk in 6 minutes. |
From baseline to month 6
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Change from baseline to month 6 in the eGFR
Tijdsspanne: From baseline to month 6
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eGFR = estimated glomerular filtration rate |
From baseline to month 6
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Change from baseline to month 6 in UACR
Tijdsspanne: From baseline to month 6
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UACR = Urinary Albumin Creatinine Ratio |
From baseline to month 6
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Change from baseline to month 6 in TSH
Tijdsspanne: From baseline to month 6
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TSH = Thyroid Stimulating Hormone |
From baseline to month 6
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Change from baseline to month 6 in KCCQ-OS score
Tijdsspanne: From baseline to month 6
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The Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) is 23-item questionnaire developed to measure health status and health-related quality of life (QoL) in individuals with heart failure. Items include heart failure symptoms, impact on physical and social functions, and how heart failure impacts QoL. |
From baseline to month 6
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Change from baseline to month 6 of EQ-5D-5L index score
Tijdsspanne: From baseline to month 6
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The EuroQol-5-Dimension-5-Level (EQ-5D-5L) includes two parts. In the first part, participants are asked to rate their current health state on 5 dimensions (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with each dimension having five levels of function (1-no problem, 2-slight problem, 3-moderate problem, 4-severe problem, and 5-extreme problem). The second part is a self-rating of current health status on a Visual Analogue Scale (EQ VAS) with endpoints labeled "best imaginable health state" (score of 100) and "worst imaginable health state" (score of 0). The scores from the 5 dimensions are used to calculate the index score. |
From baseline to month 6
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Medewerkers en onderzoekers
Sponsor
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 23026
- 2025-521831-35-00 (Register-ID: CTIS (EU))
- 2025 (Subsidie/contract van de Amerikaanse NIH)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
Currently, there is no established plan for the sharing of Individual Patient Data (IPD) from this study. The availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA 'Principles for responsible clinical trial data sharing.' This pertains to the scope, timepoint, and process of data access.
As such, Bayer commits to considering requests from qualified researchers for patient- / study-level clinical trial data, and documents from clinical trials involving medicines and indications approved in the US and EU. However, this commitment does not reflect an active IPD sharing plan. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.
Researchers can use www.vivli.org to request access to IPD and documents from clinical studies to conduct research. Information on Bayer's criteria for listing studies is provided in the member section of the portal.
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .