A Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo for Adults Participants With ATTR-CM (ATTRiumph)
13 de julio de 2026 actualizado por: AstraZeneca
A Phase IIb, Randomised, Double-blind, Placebo-controlled, Multicentre Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo in Adult Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
The purpose of this randomised, double-blind, placebo-controlled, multicenter study is to evaluate the efficacy and safety of concomitant use of eplontersen and ALXN2220 compared with eplontersen and placebo in adult participants with Transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).
Descripción general del estudio
Estado
Activo, no reclutando
Intervención / Tratamiento
Descripción detallada
This is a Phase IIb, multicenter, double-blind study in 326 participants, who will be randomized to receive either eplontersen and ALXN2220 or eplontersen and placebo once every four weeks.
Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A.
Tipo de estudio
Intervencionista
Inscripción (Estimado)
326
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
-
Berlin, Alemania, 10117
- Research Site
-
Cologne, Alemania, 50937
- Research Site
-
Essen, Alemania, 45147
- Research Site
-
Hamburg, Alemania, 22767
- Research Site
-
Heidelberg, Alemania, 69120
- Research Site
-
Homburg, Alemania, 66421
- Research Site
-
München, Alemania, 81377
- Research Site
-
Münster, Alemania, 48149
- Research Site
-
-
-
-
Alberta
-
Calgary, Alberta, Canadá, T2N 4Z6
- Research Site
-
-
British Columbia
-
Vancouver, British Columbia, Canadá, V6Z 1Y6
- Research Site
-
-
Nova Scotia
-
Halifax, Nova Scotia, Canadá, B3H 3A7
- Research Site
-
-
Ontario
-
London, Ontario, Canadá, N6A 5A5
- Research Site
-
Toronto, Ontario, Canadá, M5G 2C4
- Research Site
-
-
Quebec
-
Montreal, Quebec, Canadá, H1T 1C8
- Research Site
-
-
-
-
-
Barcelona, España, 08035
- Research Site
-
Jaén, España, 23007
- Research Site
-
L'Hospitalet de Llobregat, España, 08907
- Research Site
-
Majadahonda, España, 28222
- Research Site
-
Málaga, España, 29010
- Research Site
-
Pamplona, España, 31008
- Research Site
-
Salamanca, España, 37007
- Research Site
-
Valencia, España, 46010
- Research Site
-
-
-
-
California
-
La Jolla, California, Estados Unidos, 92037
- Research Site
-
San Francisco, California, Estados Unidos, 94115
- Research Site
-
Stanford, California, Estados Unidos, 94305
- Research Site
-
-
Colorado
-
Aurora, Colorado, Estados Unidos, 80045
- Research Site
-
-
District of Columbia
-
Washington D.C., District of Columbia, Estados Unidos, 20010
- Research Site
-
-
Florida
-
Jacksonville, Florida, Estados Unidos, 32224
- Research Site
-
Miami, Florida, Estados Unidos, 33176
- Research Site
-
Weston, Florida, Estados Unidos, 33331
- Research Site
-
-
Illinois
-
Chicago, Illinois, Estados Unidos, 60637
- Research Site
-
-
Massachusetts
-
Boston, Massachusetts, Estados Unidos, 02115
- Research Site
-
-
Missouri
-
Kansas City, Missouri, Estados Unidos, 64111
- Research Site
-
St Louis, Missouri, Estados Unidos, 63110
- Research Site
-
-
New York
-
New York, New York, Estados Unidos, 10032
- Research Site
-
-
North Carolina
-
Chapel Hill, North Carolina, Estados Unidos, 27599
- Research Site
-
Durham, North Carolina, Estados Unidos, 27710
- Research Site
-
-
Ohio
-
Cleveland, Ohio, Estados Unidos, 44195
- Research Site
-
-
Oregon
-
Portland, Oregon, Estados Unidos, 97239
- Research Site
-
-
Pennsylvania
-
Danville, Pennsylvania, Estados Unidos, 17822
- Research Site
-
Philadelphia, Pennsylvania, Estados Unidos, 19104
- Research Site
-
-
Tennessee
-
Germantown, Tennessee, Estados Unidos, 38138
- Research Site
-
-
Texas
-
Dallas, Texas, Estados Unidos, 75390
- Research Site
-
Houston, Texas, Estados Unidos, 77030
- Research Site
-
-
Utah
-
Salt Lake City, Utah, Estados Unidos, 84132
- Research Site
-
-
Virginia
-
Falls Church, Virginia, Estados Unidos, 22042
- Research Site
-
-
-
-
-
Créteil, Francia, 94010
- Research Site
-
Marseille, Francia, 13005
- Research Site
-
Rennes, Francia, 35033
- Research Site
-
Toulouse, Francia, 31059
- Research Site
-
-
-
-
-
Bologna, Italia, 40138
- Research Site
-
Florence, Italia, 50134
- Research Site
-
Milan, Italia, 20138
- Research Site
-
Padova, Italia, 35128
- Research Site
-
Pavia, Italia, 27100
- Research Site
-
Pisa, Italia, 56124
- Research Site
-
Torino, Italia, 10154
- Research Site
-
Torrette - Ancona, Italia, 60126
- Research Site
-
Trieste, Italia, IT-34149
- Research Site
-
-
-
-
-
Bunkyō City, Japón, 113-8431
- Research Site
-
Kurume-shi, Japón, 830-0011
- Research Site
-
Sapporo, Japón, 060-8543
- Research Site
-
Shinjuku-ku, Japón, 160-8582
- Research Site
-
Suita, Japón, 565-8565
- Research Site
-
-
-
-
-
Beijing, Porcelana, 100730
- Research Site
-
Beijing, Porcelana, 100034
- Research Site
-
Changsha, Porcelana, 410012
- Research Site
-
Chongqing, Porcelana, 400042
- Research Site
-
Guangzhou, Porcelana, 510080
- Research Site
-
Hangzhou, Porcelana, 310009
- Research Site
-
-
-
-
-
London, Reino Unido, NW3 2QG
- Research Site
-
London, Reino Unido, NW10 2PB
- Research Site
-
-
-
-
-
Gothenburg, Suecia, 413 45
- Research Site
-
Lund, Suecia, 22242
- Research Site
-
Stockholm, Suecia, 171 64
- Research Site
-
Uppsala, Suecia, 751 85
- Research Site
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Descripción
Capable of giving informed consent.
Inclusion Criteria:
- Participant must be ≥ 18 years to ≤ 85 years at the time of signing the informed consent.
Participants who have a diagnosis of ATTR-CM with either wild-type or variant TTR genotype based on 1 of the following:
- Endomyocardial biopsy with confirmatory TTR amyloid typing OR
- Grade 2 or 3 cardiac uptake on 99mTc scintigraphy in the absence of monoclonal gammopathy OR
- Grade 2 or 3 cardiac uptake on 99mTc scintigraphy AND confirmatory TTR amyloid typing in the presence of monoclonal gammopathy.
- NYHA Class I to III at Screening and life expectancy of ≥ 1 year as per the Investigator's judgement.
- End-diastolic IVST ≥ 12 mm on echocardiography.
- NT-proBNP ≥ 600pg/mL for participants without ongoing atrial fibrillation/flutter at Screening or NT-proBNP ≥ 1200pg/mL for participants with ongoing atrial fibrillation/flutter at Screening.
Able to complete symptom-limited maximal CPET at Screening based on the following test criteria:
- Able to exercise to near exhaustion during CPET as exhibited by RER ≥ 1.0 during symptom-limited CPET conducted during screening.
- If participant does not achieve RER ≥1.0, the CPET may be repeated once, at least 48 hours but less than 2 weeks (but before randomization) after the initial test.
- Treated according to locally recognised guidelines on standard-of-care treatment for patients with HF. Therapy should have been individually optimised and stable for ≥ 4 weeks (except diuretics) and include, unless contraindicated or not tolerated, treatment of high BP (targeting SBP < 130 mmHg as suggested in 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America HF guidelines), and ischaemic heart disease.
- Willingness to adhere to daily self-administered vitamin A supplementation (3000 IU).
Exclusion Criteria:
- Known leptomeningeal amyloidosis.
- Known light chain (AL) or secondary (amyloid A) amyloidosis, or any other form of systemic amyloidosis.
- Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy primarily due to hypertension, valvular heart disease, or ischaemic heart disease per Investigator's assessment.
- Acute coronary syndrome, unstable angina, stroke, transient ischaemic attack, coronary revascularisation, cardiac device implantation, cardiac valve repair, or major surgery within 12 weeks of Screening.
- Uncontrolled hypertension (average resting SBP > 160 mmHg or DBP > 100 mmHg at Screening).
- Average resting SBP < 90 mmHg or symptomatic orthostatic hypotension, despite appropriate treatment, at Screening per Investigator's assessment.
- Uncontrolled ventricular clinically significant cardiac arrhythmia, per Investigator's assessment.
- Left ventricular ejection fraction < 30% on echocardiography measured locally at Screening.
- Severe pulmonary impairment (SpO₂ < 92%) defined as resting SpO₂ below 92% on room air, measured by pulse oximetry, indicative of severe lung disease. Participants requiring supplemental oxygen to maintain SpO₂ ≥ 92%.
- Participants with renal failure requiring dialysis.
- History of solid organ transplantation or ventricular assist device or listing for heart transplantation at Screening. Note: prior history of planned corneal transplant is not an exclusion criterion.
- Suspected or known intolerance/allergy to proteins or any components of the study intervention.
Any of the following results conducted at screening:
i) Haemoglobin <8g/dL for women or <9g/dL for men. ii) Platelet count <125 X10*9/L or other disorder associated with clinically significant thrombocytopenia.
iii) ALT >2.0 X ULN iv) TBL >2.5 X ULN (participants with known Gilbert's syndrome can be included with TBL >2.5 X ULN as long as direct bilirubin is ≤ 1.5 X ULN) v) Serum retinol level < LLN vi) By CKD-EPI formula, eGFR <20 mL/min/1.73 m2 measured by the central laboratory at Screening.
- Current unstable liver or biliary disease per Investigator's assessment.
- Multiple myeloma, lymphoma, leukemia, or any malignancy or clonal stem cell disorder within the past 5 years (except basal cell or squamous epithelial carcinomas of the skin, melanoma in situ or cervical carcinoma in situ that have been curatively resected, Stage I cancer in remission, or adequately treated prostate cancer stage I, IIA, or IIB with Gleason score ≤ 3+4 and prostate-specific antigen < 20 ng/mL).
- Any prior treatment with an ATTR amyloid depleter or a TTR gene silencing agent approved or in clinical development.
- Participated in a structured exercise training programme within the 1 month prior to Screening or planned to start during the trial.
- Participation in another investigational clinical study or intake of another investigational drug within 30 calendar days or 5 half-lives of the IMP, whichever is longer before signing the ICF.
- Judgement by the Investigator that the participant should not participate in the study if the participant has a known medical or psychological condition or other risk factor that might interfere with the participant's full participation in the study, pose any additional risk for the participant, or confound the assessment of the participant or outcome of the study.
- Previous enrolment or randomisation in the present study.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Eplontersen and ALXN2220
Subcutaneous eplontersen and intravenous ALXN2220 every 4 weeks
|
Eplontersen delivered subcutaneously, once every 4 weeks
ALXN2220 delivered intravenously, once every 4 weeks
|
|
Comparador de placebos: Eplontersen and placebo
Subcutaneous eplontersen and intravenous placebo every 4 weeks
|
Eplontersen delivered subcutaneously, once every 4 weeks
Placebo delivered intravenously, once every 4 weeks
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Cardiopulmonary exercise test peak VO2
Periodo de tiempo: 52 week
|
Change from baseline in Cardiopulmonary exercise test peak VO2 at week 52
|
52 week
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
NT-proBNP
Periodo de tiempo: 52 week
|
Change from baseline in NT-proBNP at week 52
|
52 week
|
|
Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score
Periodo de tiempo: 52 week
|
Change from baseline in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at week 52. The minimum score is 0 and maximum score is 100. Higher scores indicate better health status. |
52 week
|
|
Extracellular volume
Periodo de tiempo: 52 week
|
Change from baseline in Extracellular volume (subgroup) at week 52
|
52 week
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
11 de junio de 2026
Finalización primaria (Estimado)
6 de febrero de 2029
Finalización del estudio (Estimado)
6 de febrero de 2029
Fechas de registro del estudio
Enviado por primera vez
12 de mayo de 2026
Primero enviado que cumplió con los criterios de control de calidad
19 de mayo de 2026
Publicado por primera vez (Actual)
27 de mayo de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
14 de julio de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
13 de julio de 2026
Última verificación
1 de julio de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- D8456C00001
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Marco de tiempo para compartir IPD
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles.
For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Criterios de acceso compartido de IPD
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool .
Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.
For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .