Une étude visant à en apprendre davantage sur l'évolution des taux sanguins de transthyrétine lorsque des participants atteints d'amylose à transthyrétine avec cardiomyopathie passent du tafamidis à l'acoramidis (ACO-SWITCH)
Étude prospective, monobras, de phase 4 pour évaluer l'évolution du taux sérique de transthyrétine (TTR) avec l'acoramidis chez des patients adultes atteints d'amylose à transthyrétine variante ou de type sauvage avec cardiomyopathie (ATTR-CM) préalablement traités par tafamidis
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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Estimé)
Phase
- Phase 4
Contacts et emplacements
Coordonnées de l'étude
- Nom: Bayer Clinical Trials Contact
- Numéro de téléphone: 18888422937
- E-mail: clinical-trials-contact@bayer.com
Lieux d'étude
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Berlin, Allemagne, 10365
- Retiré
- Sana Klinikum Lichtenberg - Klinik für Innere Medizin II, Schwerpunkt Kardiologie
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Hamburg, Allemagne, 20246
- Retiré
- 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, Allemagne, 89081
- Retiré
- Universitaetsklinikum Ulm | Klinik fuer Innere Medizin II
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Hesse
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Darmstadt, Hesse, Allemagne, 64287
- Pas encore de recrutement
- KVZ Kardiovaskulaeres Zentrum Darmstadt GmbH
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Mecklenburg-Vorpommern
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Greifswald, Mecklenburg-Vorpommern, Allemagne, 17475
- Retiré
- 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, Allemagne, 53127
- Retiré
- Universitätsklinikum Bonn - Herzzentrum des Universitätsklinikums Bonn
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Brussels Capital
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Brussels, Brussels Capital, Belgique, 1070
- Pas encore de recrutement
- Hôpital Erasme/Erasmus Ziekenhuis
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West Flanders
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Bruges, West Flanders, Belgique, 8000
- Pas encore de recrutement
- AZ St-Jan Brugge-Oostende A.V.
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Naples, Italie, 80131
- Pas encore de recrutement
- Azienda Ospedaliera Dei Colli_Monaldi - Malattie Rare e Genetiche Cardiovascolari
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Apulia
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Lecce, Apulia, Italie, 73100
- Pas encore de recrutement
- Ospedale Vito Fazzi Lecce_Cardiologia e UTIC
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Emilia-Romagna
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Bologna, Emilia-Romagna, Italie, 40138
- Pas encore de recrutement
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS_Policlinico Sant'Orsola_Cardiologia
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Lombardy
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Bergamo, Lombardy, Italie, 24127
- Recrutement
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII - Cardiologia 1
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Milan, Lombardy, Italie, 20138
- Recrutement
- Centro Cardiologico Monzino S.p.A. - Cardiologia Peri-Operatoria e Imaging Cardiovascolare
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Pavia, Lombardy, Italie, 27100
- Pas encore de recrutement
- 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, Italie, 50134
- Recrutement
- Careggi University Hospital_cardio intensive care unit
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Pisa, Tuscany, Italie, 56124
- Recrutement
- Fondazione Toscana Gabriele Monasterio_Pisa - Cardiologia e Medicina Cardiovascolare
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Siena, Tuscany, Italie, 53100
- Recrutement
- Azienda Ospedaliera Universitaria Senese - cardiologia
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Veneto
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Padova, Veneto, Italie, 35128
- Recrutement
- Azienda Ospedale-Università di Padova-UOC Cardiologia
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Lower Austria
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Sankt Pölten, Lower Austria, L'Autriche, 1210
- Retiré
- 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, L'Autriche, 3500
- Pas encore de recrutement
- Klinik Ottakring - 3. Medizinische Abteilung mit Kardiologie, internistischer Intensivmedizin und Ambulanz
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Vienna, State of Vienna, L'Autriche, 1090
- Recrutement
- Medizinische Universität Wien- Universitätsklinik für Innere Medizin II, Klinische Abteilung für Kardiologie
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Vienna, State of Vienna, L'Autriche, 1100
- Recrutement
- Klinik Favoriten - 5.Medizinische Abteilung-Kardiologie
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Styria
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Vienna, Styria, L'Autriche, 1030
- Recrutement
- Medizinische Universität Graz- Klinische Abteilung für Kardiologie
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Upper Austria
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Braunau am Inn, Upper Austria, L'Autriche, 5280
- Recrutement
- Krankenhaus St. Josef Braunau | Innere Medizin I
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Vorarlberg
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Feldkirch, Vorarlberg, L'Autriche, 6800
- Retiré
- VIVIT - Landeskrankenhaus Feldkirch - Innere Medizin I, Kardiologie, Angiologie, Endokrinologie, Diabetologie, Intensivmedizin
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Oslo, Norvège, 0424
- Pas encore de recrutement
- Oslo Universitetssykehus HF, Rikshospitalet
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Change in serum TTR level from baseline to month 6 or premature discontinuation of treatment
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Nombre de participants avec des TEAEs et des TEAEs graves
Délai: Depuis la première administration du médicament de l'étude jusqu'à 30 jours après la dernière dose du médicament de l'étude ou jusqu'à la fin de l'étude, selon ce qui survient en premier
|
Depuis la première administration du médicament de l'étude jusqu'à 30 jours après la dernière dose du médicament de l'étude ou jusqu'à la fin de l'étude, selon ce qui survient en premier
|
|
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Changement par rapport à la valeur initiale jusqu'au mois 6 de la créatinine
Délai: De la valeur initiale au mois 6
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De la valeur initiale au mois 6
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Évolution de la cystatine C par rapport à la valeur de base à 6 mois
Délai: De la valeur initiale au mois 6
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De la valeur initiale au mois 6
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Change in serum TTR level from baseline to week 1, 2, 3, 4 and at month 3.
Délai: At baseline, week 1, 2, 3, 4 and at month 3
|
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
Délai: From baseline to month 6
|
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
Délai: 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
Délai: From baseline to month 6
|
RBP4 = Retinol Binding Protein 4 |
From baseline to month 6
|
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Signs of cardiac remodeling from baseline to month 6
Délai: From baseline to month 6
|
These signs will be measured by echocardiogram |
From baseline to month 6
|
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Change from baseline to month 6 in 6MWD
Délai: From baseline to month 6
|
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
Délai: From baseline to month 6
|
eGFR = estimated glomerular filtration rate |
From baseline to month 6
|
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Change from baseline to month 6 in UACR
Délai: From baseline to month 6
|
UACR = Urinary Albumin Creatinine Ratio |
From baseline to month 6
|
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Change from baseline to month 6 in TSH
Délai: From baseline to month 6
|
TSH = Thyroid Stimulating Hormone |
From baseline to month 6
|
|
Change from baseline to month 6 in KCCQ-OS score
Délai: From baseline to month 6
|
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
Délai: From baseline to month 6
|
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
|
Collaborateurs et enquêteurs
Parrainer
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 23026
- 2025-521831-35-00 (Identificateur de registre: CTIS (EU))
- 2025 (Subvention/contrat des NIH des États-Unis)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
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.
Informations sur les médicaments et les dispositifs, documents d'étude
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