トランスサイレチンアミロイドーシス心筋症患者がタファミジスからアコラミジスに切り替えた際の血中トランスサイレチンレベルの変化に関する研究 (ACO-SWITCH)
タファミジスで事前治療を受けた変異型または野生型トランスサイレチンアミロイドーシス心筋症（ATTR-CM）の成人患者におけるアコラミジス投与時の血清トランスサイレチン（TTR）レベル推移を評価する前向き単群第4相試験
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.
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ 4
連絡先と場所
研究連絡先
- 名前：Bayer Clinical Trials Contact
- 電話番号：18888422937
- メール：clinical-trials-contact@bayer.com
研究場所
-
-
-
Naples、イタリア、80131
- まだ募集していません
- Azienda Ospedaliera Dei Colli_Monaldi - Malattie Rare e Genetiche Cardiovascolari
-
-
Apulia
-
Lecce、Apulia、イタリア、73100
- まだ募集していません
- Ospedale Vito Fazzi Lecce_Cardiologia e UTIC
-
-
Emilia-Romagna
-
Bologna、Emilia-Romagna、イタリア、40138
- まだ募集していません
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS_Policlinico Sant'Orsola_Cardiologia
-
-
Lombardy
-
Bergamo、Lombardy、イタリア、24127
- 募集
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII - Cardiologia 1
-
Milan、Lombardy、イタリア、20138
- 募集
- Centro Cardiologico Monzino S.p.A. - Cardiologia Peri-Operatoria e Imaging Cardiovascolare
-
Pavia、Lombardy、イタリア、27100
- まだ募集していません
- Fondazione IRCCS Policlinico San Matteo-SC Medicina Generale 2 - Centro Amiloidosi Sistemiche e Malattie ad Alta Complessità
-
-
Tuscany
-
Florence、Tuscany、イタリア、50134
- 募集
- Careggi University Hospital_cardio intensive care unit
-
Pisa、Tuscany、イタリア、56124
- 募集
- Fondazione Toscana Gabriele Monasterio_Pisa - Cardiologia e Medicina Cardiovascolare
-
Siena、Tuscany、イタリア、53100
- 募集
- Azienda Ospedaliera Universitaria Senese - cardiologia
-
-
Veneto
-
Padova、Veneto、イタリア、35128
- 募集
- Azienda Ospedale-Università di Padova-UOC Cardiologia
-
-
-
-
Lower Austria
-
Sankt Pölten、Lower Austria、オーストリア、1210
- 引きこもった
- Universitätsklinikum St. Pölten - Lilienfeld - Klinische Abteilung für Innere Medizin 3
-
-
State of Vienna
-
Vienna、State of Vienna、オーストリア、3500
- まだ募集していません
- Klinik Ottakring - 3. Medizinische Abteilung mit Kardiologie, internistischer Intensivmedizin und Ambulanz
-
Vienna、State of Vienna、オーストリア、1090
- 募集
- Medizinische Universität Wien- Universitätsklinik für Innere Medizin II, Klinische Abteilung für Kardiologie
-
Vienna、State of Vienna、オーストリア、1100
- 募集
- Klinik Favoriten - 5.Medizinische Abteilung-Kardiologie
-
-
Styria
-
Vienna、Styria、オーストリア、1030
- 募集
- Medizinische Universität Graz- Klinische Abteilung für Kardiologie
-
-
Upper Austria
-
Braunau am Inn、Upper Austria、オーストリア、5280
- 募集
- Krankenhaus St. Josef Braunau | Innere Medizin I
-
-
Vorarlberg
-
Feldkirch、Vorarlberg、オーストリア、6800
- 引きこもった
- VIVIT - Landeskrankenhaus Feldkirch - Innere Medizin I, Kardiologie, Angiologie, Endokrinologie, Diabetologie, Intensivmedizin
-
-
-
-
-
Berlin、ドイツ、10365
- 引きこもった
- Sana Klinikum Lichtenberg - Klinik für Innere Medizin II, Schwerpunkt Kardiologie
-
Hamburg、ドイツ、20246
- 引きこもった
- Universitätsklinikum Hamburg Eppendorf (UKE)-Universitären Herz- und Gefäßzentrum Hamburg, Klinik für Kardiologie
-
-
Baden-Wurttemberg
-
Ulm、Baden-Wurttemberg、ドイツ、89081
- 引きこもった
- Universitaetsklinikum Ulm | Klinik fuer Innere Medizin II
-
-
Hesse
-
Darmstadt、Hesse、ドイツ、64287
- まだ募集していません
- KVZ Kardiovaskulaeres Zentrum Darmstadt GmbH
-
-
Mecklenburg-Vorpommern
-
Greifswald、Mecklenburg-Vorpommern、ドイツ、17475
- 引きこもった
- Universitaetsmedizin Greifswald KöR- Klinik und Poliklinik für Innere Medizin B
-
-
North Rhine-Westphalia
-
Bonn、North Rhine-Westphalia、ドイツ、53127
- 引きこもった
- Universitätsklinikum Bonn - Herzzentrum des Universitätsklinikums Bonn
-
-
-
-
-
Oslo、ノルウェー、0424
- まだ募集していません
- Oslo Universitetssykehus HF, Rikshospitalet
-
-
-
-
Brussels Capital
-
Brussels、Brussels Capital、ベルギー、1070
- まだ募集していません
- Hôpital Erasme/Erasmus Ziekenhuis
-
-
West Flanders
-
Bruges、West Flanders、ベルギー、8000
- まだ募集していません
- AZ St-Jan Brugge-Oostende A.V.
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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.
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in serum TTR level from baseline to month 6 or premature discontinuation of treatment
時間枠：From baseline to month 6 or premature discontinuation of treatment
|
TTR = Transthyretin |
From baseline to month 6 or premature discontinuation of treatment
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
TEAEおよび重篤なTEAEを発現した参加者数
時間枠：初回の試験薬投与から、最終試験薬投与後30日目まで、または試験終了まで、いずれか早い方
|
初回の試験薬投与から、最終試験薬投与後30日目まで、または試験終了まで、いずれか早い方
|
|
|
ベースラインから6ヶ月後までのクレアチニンの変化
時間枠：ベースラインから6か月まで
|
ベースラインから6か月まで
|
|
|
ベースラインから6ヵ月後のシスタチンCの変化
時間枠：ベースラインから6か月目まで
|
ベースラインから6か月目まで
|
|
|
Change in serum TTR level from baseline to week 1, 2, 3, 4 and at month 3.
時間枠：At baseline, week 1, 2, 3, 4 and at month 3
|
TTR = Transthyretin |
At baseline, week 1, 2, 3, 4 and at month 3
|
|
Change from baseline to month 6 of NT-proBNP
時間枠：From baseline to month 6
|
NT-proBNP = N-terminal pro-B-type Natriuretic Peptide |
From baseline to month 6
|
|
Change from baseline to month 6 of hs-TnT
時間枠：From baseline to month 6
|
hs-TNT = high-sensitivity Troponin T |
From baseline to month 6
|
|
Change from baseline to month 6 of RBP4
時間枠：From baseline to month 6
|
RBP4 = Retinol Binding Protein 4 |
From baseline to month 6
|
|
Signs of cardiac remodeling from baseline to month 6
時間枠：From baseline to month 6
|
These signs will be measured by echocardiogram |
From baseline to month 6
|
|
Change from baseline to month 6 in 6MWD
時間枠：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
|
|
Change from baseline to month 6 in the eGFR
時間枠：From baseline to month 6
|
eGFR = estimated glomerular filtration rate |
From baseline to month 6
|
|
Change from baseline to month 6 in UACR
時間枠：From baseline to month 6
|
UACR = Urinary Albumin Creatinine Ratio |
From baseline to month 6
|
|
Change from baseline to month 6 in TSH
時間枠：From baseline to month 6
|
TSH = Thyroid Stimulating Hormone |
From baseline to month 6
|
|
Change from baseline to month 6 in KCCQ-OS score
時間枠：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
|
|
Change from baseline to month 6 of EQ-5D-5L index score
時間枠：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
|
協力者と研究者
スポンサー
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 23026
- 2025-521831-35-00 (レジストリ識別子：CTIS (EU))
- 2025 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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.
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。