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. juli 2026 oppdatert av: 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).
Studieoversikt
Status
Aktiv, ikke rekrutterende
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Intervensjonell
Registrering (Antatt)
326
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Alberta
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Calgary, Alberta, Canada, T2N 4Z6
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British Columbia
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Vancouver, British Columbia, Canada, V6Z 1Y6
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 3A7
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Ontario
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London, Ontario, Canada, N6A 5A5
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Toronto, Ontario, Canada, M5G 2C4
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Quebec
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Montreal, Quebec, Canada, H1T 1C8
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California
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La Jolla, California, Forente stater, 92037
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San Francisco, California, Forente stater, 94115
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Stanford, California, Forente stater, 94305
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Colorado
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Aurora, Colorado, Forente stater, 80045
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District of Columbia
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Washington D.C., District of Columbia, Forente stater, 20010
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Florida
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Jacksonville, Florida, Forente stater, 32224
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Miami, Florida, Forente stater, 33176
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Weston, Florida, Forente stater, 33331
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Illinois
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Chicago, Illinois, Forente stater, 60637
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Massachusetts
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Boston, Massachusetts, Forente stater, 02115
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Missouri
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Kansas City, Missouri, Forente stater, 64111
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St Louis, Missouri, Forente stater, 63110
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New York
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New York, New York, Forente stater, 10032
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North Carolina
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Chapel Hill, North Carolina, Forente stater, 27599
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Durham, North Carolina, Forente stater, 27710
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Ohio
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Cleveland, Ohio, Forente stater, 44195
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Oregon
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Portland, Oregon, Forente stater, 97239
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Pennsylvania
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Danville, Pennsylvania, Forente stater, 17822
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Philadelphia, Pennsylvania, Forente stater, 19104
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Tennessee
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Germantown, Tennessee, Forente stater, 38138
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Texas
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Dallas, Texas, Forente stater, 75390
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Houston, Texas, Forente stater, 77030
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Utah
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Salt Lake City, Utah, Forente stater, 84132
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Virginia
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Falls Church, Virginia, Forente stater, 22042
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Créteil, Frankrike, 94010
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Marseille, Frankrike, 13005
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Rennes, Frankrike, 35033
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Toulouse, Frankrike, 31059
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Bologna, Italia, 40138
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Florence, Italia, 50134
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Milan, Italia, 20138
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Padova, Italia, 35128
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Pavia, Italia, 27100
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Pisa, Italia, 56124
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Torino, Italia, 10154
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Torrette - Ancona, Italia, 60126
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Trieste, Italia, IT-34149
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Bunkyō City, Japan, 113-8431
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Kurume-shi, Japan, 830-0011
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Sapporo, Japan, 060-8543
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Shinjuku-ku, Japan, 160-8582
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Suita, Japan, 565-8565
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Beijing, Kina, 100730
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Beijing, Kina, 100034
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Changsha, Kina, 410012
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Chongqing, Kina, 400042
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Guangzhou, Kina, 510080
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Hangzhou, Kina, 310009
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Barcelona, Spania, 08035
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Jaén, Spania, 23007
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L'Hospitalet de Llobregat, Spania, 08907
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Majadahonda, Spania, 28222
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Málaga, Spania, 29010
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Pamplona, Spania, 31008
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Salamanca, Spania, 37007
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Valencia, Spania, 46010
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London, Storbritannia, NW3 2QG
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London, Storbritannia, NW10 2PB
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Gothenburg, Sverige, 413 45
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Lund, Sverige, 22242
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Stockholm, Sverige, 171 64
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Uppsala, Sverige, 751 85
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Berlin, Tyskland, 10117
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Cologne, Tyskland, 50937
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Essen, Tyskland, 45147
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Hamburg, Tyskland, 22767
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Heidelberg, Tyskland, 69120
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Homburg, Tyskland, 66421
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München, Tyskland, 81377
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Münster, Tyskland, 48149
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: Eplontersen and ALXN2220
Subcutaneous eplontersen and intravenous ALXN2220 every 4 weeks
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Eplontersen delivered subcutaneously, once every 4 weeks
ALXN2220 delivered intravenously, once every 4 weeks
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Placebo komparator: Eplontersen and placebo
Subcutaneous eplontersen and intravenous placebo every 4 weeks
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Eplontersen delivered subcutaneously, once every 4 weeks
Placebo delivered intravenously, once every 4 weeks
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Cardiopulmonary exercise test peak VO2
Tidsramme: 52 week
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Change from baseline in Cardiopulmonary exercise test peak VO2 at week 52
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52 week
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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NT-proBNP
Tidsramme: 52 week
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Change from baseline in NT-proBNP at week 52
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52 week
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Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score
Tidsramme: 52 week
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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
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Extracellular volume
Tidsramme: 52 week
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Change from baseline in Extracellular volume (subgroup) at week 52
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52 week
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
11. juni 2026
Primær fullføring (Antatt)
6. februar 2029
Studiet fullført (Antatt)
6. februar 2029
Datoer for studieregistrering
Først innsendt
12. mai 2026
Først innsendt som oppfylte QC-kriteriene
19. mai 2026
Først lagt ut (Faktiske)
27. mai 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
14. juli 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
13. juli 2026
Sist bekreftet
1. juli 2026
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- D8456C00001
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
JA
IPD-planbeskrivelse
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.
IPD-delingstidsramme
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.
Tilgangskriterier for IPD-deling
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.
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Ja
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .