Clinical trial • Phase III • Immunology|Haematology|Cardiology

ANSELAMIMAB for AL amyloidosis | Cardiac AL amyloidosis (Mayo stage IIIb)

Phase III trial of ANSELAMIMAB for AL amyloidosis | Cardiac AL amyloidosis (Mayo stage IIIb).

Overview

Trial Therapeutic Area
Immunology|Haematology|Cardiology
Trial Disease
AL amyloidosis | Cardiac AL amyloidosis (Mayo stage IIIb)
Trial Stage
Phase III
Drug Modality
Monoclonal antibody|Other
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
04-04-2024
First CTIS Authorization Date
09-05-2024

Trial design

Randomised, placebo arm: sodium chloride (0.9% nacl) solution for infusion (intravenous) as placebo plus standard-of-care plasma cell dyscrasia treatment (cybord-based regimen). test arm: cael-101 (anselamimab) intravenous infusion plus standard-of-care plasma cell dyscrasia treatment (cybord-based regimen). exact cael-101 dosing schedule not specified in the available data; placebo is described as isotonic saline (0.9% nacl) intravenous infusion.-controlled Phase III trial in Greece, Austria, Poland and others.

Randomised
Yes
Comparator
Placebo arm: SODIUM CHLORIDE (0.9% NaCl) solution for infusion (intravenous) as placebo plus standard-of-care plasma cell dyscrasia treatment (CyBorD-based regimen). Test arm: CAEL-101 (anselamimab) intravenous infusion plus standard-of-care plasma cell dyscrasia treatment (CyBorD-based regimen). Exact CAEL-101 dosing schedule not specified in the available data; placebo is described as isotonic saline (0.9% NaCl) intravenous infusion.
Target Sample Size
69

Eligibility

Recruits 69 The record indicates a vulnerable population was selected (isVulnerablePopulationSelected = true). Informed consent is required: each patient will be assigned a unique identifier after signing the Informed Consent Form (ICF). Country-specific subject information and ICF documents are provided (multiple language versions listed in the documents). There is no explicit text describing assent or consent by a legally authorised representative in the available data..

Pregnancy Exclusion
Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective contraception from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of her PCD therapy, whichever is longer
Vulnerable Population
The record indicates a vulnerable population was selected (isVulnerablePopulationSelected = true). Informed consent is required: each patient will be assigned a unique identifier after signing the Informed Consent Form (ICF). Country-specific subject information and ICF documents are provided (multiple language versions listed in the documents). There is no explicit text describing assent or consent by a legally authorised representative in the available data.

Inclusion criteria

  • {"criterion_text":"- AL amyloidosis stage IIIb based on the European Modification of the 2004 Standard Mayo Clinic Staging at the time of Screening, which includes NT-proBNP > 8,500 ng/L.\n- Measurable hematologic disease at Screening as defined by at least one of the following: a. Involved/uninvolved free light chain difference (dFLC) > 4 mg/dL OR b. Involved free light chain (iFLC) > 4 mg/dL with abnormal Kappa/Lambda ratio OR c. Serum protein electrophoresis (SPEP) m-spike > 0.5 g/dL\n- Histopathological diagnosis of amyloidosis based on polarizing light microscopy of green bi-refringent material in Congo red stained tissue specimens AND confirmation of AL derived amyloid deposits by at least one of the following: a. Immunohistochemistry/Immunofluorescence OR b. Mass spectrometry OR c. Characteristic electron microscopy appearance/Immunoelectron microscopy\n- Cardiac involvement as defined by: a. Documented clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure AND b. At least one of the following: I. Endomyocardial biopsy demonstrating AL cardiac amyloidosis OR ii. Echocardiogram demonstrating a mean left ventricular wall thickness (calculated as [IVSd+LPWd]/2) of > 12 mm at diastole in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening OR iii. Cardiac magnetic resonance imaging (MRI) with gadolinium contrast agent diagnostic of cardiac amyloidosis\n- Planned first-line treatment for plasma cell dyscrasia is cyclophosphamide-bortezomib-dexamethasone (CyBorD)-based regimen administered as SoC.\n- Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective contraception from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of her PCD therapy, whichever is longer\n- Men must be surgically sterile or must agree to use highly effective contraception and refrain from donating sperm from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of their PCD therapy, whichever is longer"}

Exclusion criteria

  • {"criterion_text":"- Have any other form of amyloidosis other than AL amyloidosis\n- Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 2 weeks of a CyBorD-based PCD treatment after Screening laboratory samples are obtained and prior to randomization is allowed.\n- Has POEMS syndrome OR multiple myeloma defined as clonal bone marrow plasma cells > 10% from a bone marrow biopsy (performed ≤ 3 months prior to signing the ICF or during Screening) OR biopsy-proven (performed ≤ 3 months prior to signing the ICF or during Screening) bony or extramedullary plasmacytoma AND any one or more of the following CRAB features: a. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, (eg, multiple myeloma and POEMS syndrome), specifically: i. Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the ULN or > 2.75 mmol/L (> 11 mg/dL) OR ii. Renal insufficiency: creatinine clearance < 40 mL per minute or serum creatinine > 177 μmol/L (> 2 mg/dL) OR iii. Anemia: hemoglobin value of > 20 g/L below the lowest limit of normal, or a hemoglobin value < 100 g/L OR iv. Bone lesions: one or more osteolytic lesion on imaging tests (performed ≤ 3 months prior to signing the ICF or during Screening): skeletal radiography, CT, or PET/CT, or MRI. If bone marrow has < 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement OR b. Any one of the following biomarkers of malignancy: i. 60% or greater clonal plasma cells on bone marrow examination OR ii. More than one focal lesion on MRI that is at least 5mm or greater in size\n- Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- A hierarchical combination of time to all-cause Mortality (ACM) and the frequency of cardiovascular hospitalizations (CVH). Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). Changes from baseline in vital signs, weight, clinical laboratory tests, and 12-lead electrocardiograms (ECGs).","definition_or_measurement_approach":"Primary endpoint is a hierarchical combination: time-to-event analysis for time to all-cause mortality (ACM) and count/frequency analysis for cardiovascular-related hospitalizations (CVH). Safety assessed by incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Additional assessments are changes from baseline in vital signs, weight, clinical laboratory tests and 12-lead ECGs."}

Secondary endpoints

  • {"endpoint_text":"- Time to ACM in Primary Evaluation Treatment Period (PETP)","definition_or_measurement_approach":"Time-to-event analysis measuring time from randomization (or treatment initiation) to all-cause mortality during the PETP."}
  • {"endpoint_text":"- Frequency of CVH in PETP","definition_or_measurement_approach":"Count/frequency of cardiovascular-related hospitalizations during the PETP."}
  • {"endpoint_text":"- Changes from baseline to Week 50 in the KCCQ-OS.","definition_or_measurement_approach":"Change from baseline to Week 50 in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS)."}
  • {"endpoint_text":"- Change from baseline to Week 50 in NTproBNP","definition_or_measurement_approach":"Change from baseline to Week 50 in NT-proBNP blood concentration."}
  • {"endpoint_text":"- Changes from baseline to Week 50 in GLS%.","definition_or_measurement_approach":"Change from baseline to Week 50 in global longitudinal strain percentage (GLS%) measured by echocardiography."}
  • {"endpoint_text":"- Changes from baseline to Week 50 in the 6MWT","definition_or_measurement_approach":"Change from baseline to Week 50 in distance walked in the six-minute walk test (6MWT)."}
  • {"endpoint_text":"- Change from baseline to Week 50 in the SF-36v2 PCS","definition_or_measurement_approach":"Change from baseline to Week 50 in the Short Form 36 Health Survey Physical Component Score (SF-36v2 PCS)."}

Recruitment

Planned Sample Size
69
Recruitment Window Months
77
Consent Approach
Informed consent is required; each patient signs an Informed Consent Form (ICF) and is assigned a unique identifier thereafter. Country-specific ICF and subject information documents are provided (documents include multiple language versions such as Greek, German, Polish, Czech, Spanish, French, Italian, Dutch, English). Separate 'Pregnant Partner' ICF versions are also provided in some countries. The record does not specify assent procedures or consent by legally authorised representatives in the available data.

Geography

Total Number Of Sites
43
Total Number Of Participants
56

Greece

Earliest CTIS Part Ii Submission Date
16-04-2024
Latest Decision Or Authorization Date
19-06-2024
Processing Time Days
64
Number Of Sites
2
Number Of Participants
7

Sites

Site Name
Alexandra Hospital
Department Name
Plasma Cell Dyscrasia Unit/ Therapeutic Clinic, Medical School
Contact Person Name
Efstathios Kastritis
Contact Person Email
ekastritis@med.uoa.gr
Site Name
General University Hospital Of Patras
Department Name
Hematology Department of the Department of Internal Medicine of the General Hospital of Patras
Contact Person Name
Alexandros Spyridonidis
Contact Person Email
spyridonidis@upatras.gr

Austria

Earliest CTIS Part Ii Submission Date
16-04-2024
Latest Decision Or Authorization Date
21-05-2024
Processing Time Days
35
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Ordensklinikum Linz GmbH
Department Name
Internal 1 - Hematology with stem cell transplantation, hemostaseology and medical oncology
Contact Person Name
Irene Strassl
Site Name
Medical University Of Vienna
Department Name
Department of internal Medicine I, Division of Hematology and Haemostaseology
Contact Person Name
Hermine Agis
Contact Person Email
hermine.agis@meduniwien.ac.at

Poland

Earliest CTIS Part Ii Submission Date
16-04-2024
Latest Decision Or Authorization Date
31-05-2024
Processing Time Days
45
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Uniwersyteckie Centrum Kliniczne
Department Name
Klinika Hematologii i Transplantologii
Contact Person Name
Monika Szarejko
Contact Person Email
monasza1@gumed.edu.pl
Site Name
Medical University Of Warsaw
Department Name
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
Contact Person Name
Krzysztof Jamroziak
Contact Person Email
k.m.jamroziak@gmail.com
Site Name
Uniwersytecki Szpital Kliniczny W Poznaniu
Department Name
Oddział Hematologii i Chorób Rozrostowych Układu Krwiotwórczego, Pododdział Transplantacji Szpiku
Contact Person Name
Dominik Dytfled
Contact Person Email
dytfeld@me.com

Belgium

Earliest CTIS Part Ii Submission Date
16-04-2024
Latest Decision Or Authorization Date
15-05-2024
Processing Time Days
29
Number Of Sites
2
Number Of Participants
3

Sites

Site Name
UZ Leuven
Department Name
Departement of Haematology
Contact Person Name
Michel DELFORGE
Contact Person Email
michel.delforge@uzleuven.be
Site Name
Institut Jules Bordet
Department Name
Department of Haematology
Contact Person Name
Nathalie MEULEMAN

Italy

Earliest CTIS Part Ii Submission Date
16-04-2024
Latest Decision Or Authorization Date
29-05-2024
Processing Time Days
43
Number Of Sites
4
Number Of Participants
6

Sites

Site Name
Universita' Degli Studi Di Napoli Federico II
Department Name
UOC Ematologia con TMO
Contact Person Name
Fabrizio Pane
Contact Person Email
fabrizio.pane@unina.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
UOC Medicina generale 2
Contact Person Name
Giovanni Palladini
Contact Person Email
giovanni.palladini@unipv.it
Site Name
Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
Department Name
UOS DH Ematologico
Contact Person Name
Ombretta Annibali
Contact Person Email
o.annibali@unicampus.it
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
UO Ematologia
Contact Person Name
Gabriele Buda
Contact Person Email
gabriele.buda@unipi.it

Czechia

Earliest CTIS Part Ii Submission Date
16-04-2024
Latest Decision Or Authorization Date
09-05-2024
Processing Time Days
23
Number Of Sites
2
Number Of Participants
1

Sites

Site Name
Fakultni Nemocnice Ostrava
Department Name
Klinika hematoonkologie FNO a LF OU
Contact Person Name
Roman Hájek
Contact Person Email
roman.hajek@fno.cz
Site Name
Vseobecna Fakultni Nemocnice V Praze
Department Name
Interní klinika - klinika hematologie 1.LF a VFN
Contact Person Name
František Sedlák
Contact Person Email
frantisek.sedlak@vfn.cz

Spain

Earliest CTIS Part Ii Submission Date
16-04-2024
Latest Decision Or Authorization Date
09-05-2024
Processing Time Days
23
Number Of Sites
11
Number Of Participants
8

Sites

Site Name
Clinica Universidad De Navarra
Department Name
Haematology Department
Contact Person Name
Ramon Lecumberri Villamediana
Contact Person Email
rlecumber@unav.es
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Hematology
Contact Person Name
Eusebio Narciso Martín Chacón
Site Name
Hospital Clinic De Barcelona
Department Name
Hematology
Contact Person Name
Maria Teresa Cibeira López
Contact Person Email
mcibeira@clinic.cat
Site Name
Hospital La Luz Grupo Quironsalud
Department Name
Cardiology
Contact Person Name
Roberto Martín Reyes
Contact Person Email
RmartinR@quironsalud.es
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Hematology
Contact Person Name
Francisco Javier de la Rubia Comos
Contact Person Email
delarubia_jav@gva.es
Site Name
Hospital Universitario De Salamanca
Department Name
Hematology
Contact Person Name
Verónica González de la Calle
Contact Person Email
vgcalle@saludcastillayleon.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Hematology
Contact Person Name
Mercedes Gironella Mesa
Contact Person Email
mgironel@vhebron.net
Site Name
Hospital Universitario De Cabuenes
Department Name
Hematology
Contact Person Name
Maria Esther Gonzalez García
Contact Person Email
gonzalezesther@uniovi.es
Site Name
Hospital Universitario Virgen De Las Nieves
Department Name
Hematology
Contact Person Name
María Esther Clavero Sánchez
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Hematology
Contact Person Name
Irene Romera Martinez
Contact Person Email
irene.romera@salud.madrid.org
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Hematology
Contact Person Name
Elham Askari
Contact Person Email
EAskari@quironsalud.es

Germany

Earliest CTIS Part Ii Submission Date
16-04-2024
Latest Decision Or Authorization Date
10-05-2024
Processing Time Days
24
Number Of Sites
6
Number Of Participants
9

Sites

Site Name
HOPA MVZ GmbH
Department Name
Hematology and Oncology
Contact Person Name
Timo Hansen
Contact Person Email
timon.hansen@hopa.de
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Oncology and clinical immunology
Contact Person Name
Roland Fenk
Contact Person Email
fenk@med.uni-duesseldorf.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Hematology
Contact Person Name
Alexander Carpinteiro
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Hematology, Oncology and Tumor Immunology (CBF)
Contact Person Name
Stephan Bohl
Contact Person Email
Stephan.Bohl@charite.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Internal Medicine 5, Amyloidosis Center
Contact Person Name
Stefan Schönland
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
Medical Clinic and Polyclinic II
Contact Person Name
Maximilian Johannes Steinhardt
Contact Person Email
steinhardt_M@ukw.de

France

Earliest CTIS Part Ii Submission Date
16-04-2024
Latest Decision Or Authorization Date
14-05-2024
Processing Time Days
28
Number Of Sites
11
Number Of Participants
15

Sites

Site Name
Institut Paoli Calmettes
Department Name
Departement d'Hematologie
Contact Person Name
Jean-Marc SCHIANO DE COLELLA
Contact Person Email
schianojm@ipc.unicancer.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Unité Hémopathies Lymphoïdes
Contact Person Name
Karim BELHADJ
Contact Person Email
karim.belhadj@aphp.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Service de Néphrologie-Transplantation
Contact Person Name
Antoine HUART
Contact Person Email
huart.a@chu-toulouse.fr
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Service d’Hématologie Clinique et Thérapie Cellulaire
Contact Person Name
Arnaud JACCARD
Contact Person Email
arnaud.jaccard@chu-limoges.fr
Site Name
Hospices Civils De Lyon
Department Name
Service d'hematologie clinique
Contact Person Name
Lionel KARLIN
Contact Person Email
lionel.karlin@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
Hématologie Clinique
Contact Person Name
Margaret MACRO
Contact Person Email
macro-m@chu-caen.fr
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
Service de Néphrologie et transplantation rénale
Contact Person Name
Estelle DESPORT
Site Name
Assistance Publique Hopitaux De Paris (Paris site)
Department Name
Service d’Immuno-Hématologie
Contact Person Name
Bertrand ARNULF
Contact Person Email
bertrand.arnulf@aphp.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Service de médecine interne et maladies infectieuses
Contact Person Name
Jean-François VIALLARD
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Département d’Hématologie
Contact Person Name
Salomon MANIER
Contact Person Email
salomon.manier@chru-lille.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Hématologie et Thérapie cellulaire
Contact Person Name
Thomas CHALOPIN
Contact Person Email
t.chalopin@chu-tours.fr

Sponsor

Primary sponsor

Full Name
Alexion Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
IQVIA Limited
Responsibilities
Maintain eTMF, manage ePRO and Central Lab, Periodic safety reporting responsibilities to Investigators in France; multiple sponsorDuties codes listed
Name
Almac Clinical Services LLC
Responsibilities
Sponsor duties listed (code 14) — specific textual responsibility not provided in dataset
Name
Labcorp Central Laboratory Services S.a.r.l.
Responsibilities
Statistical programming, biostatistical support
Name
Biotel Research LLC
Responsibilities
ECG analysis/review
Name
Signant Health LLC
Responsibilities
Electronic patient-reported outcome (ePRO)
Name
4g Clinical LLC
Responsibilities
Sponsor duties listed (code 3) — specific textual responsibility not provided in dataset
Name
Medidata Solutions Inc.
Responsibilities
Sponsor duties listed (code 7) — specific textual responsibility not provided in dataset
Name
IQVIA RDS Hellas Single Member S.A.
Responsibilities
Sponsor duties listed (codes 1,12,2) — specific textual responsibilities not provided in dataset

Third parties

  • {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"Statistical programming, biostatistical support; sponsorDuties codes: 15, 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Biotel Research LLC","duties_or_roles":"ECG analysis/review","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Multiple roles including: maintain eTMF, manage ePRO and Central Lab, Periodic safety reporting responsibilities to Investigators in France; sponsorDuties codes: 1,12,13,15,2,5,6,9","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"Electronic patient-reported outcome (ePRO)","organisation_type":"Pharmaceutical company"}
  • {"country":"Greece","full_name":"IQVIA RDS Hellas Single Member S.A.","duties_or_roles":"sponsorDuties codes: 1,12,2","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Resolian Bioanalytics","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Industry"}
  • {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Yourway Transport Inc.","duties_or_roles":"Management/Shipment of standard of care CyBorD for those sites that require it; sponsorDuties codes: 14, 15","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"The Brigham And Women’s Hospital Inc.","duties_or_roles":"Echocardiogram (GLS%)","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp (listed above as Labcorp Central Laboratory Services S.a.r.l.)","duties_or_roles":"Central laboratory and statistical support (as listed)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
CAEL-101
Active Substance
ANSELAMIMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous use
Route
Intravenous
Authorisation Status
Not authorised
Orphan Designation
Yes
Maximum Dose
1000 mg/m2
Investigational Product Name
SODIUM CHLORIDE
Active Substance
POTASSIUM CHLORIDE PH. EUR., SODIUM CHLORIDE PH. EUR.
Modality
Other
Routes Of Administration
Intravenous use
Route
Intravenous
Authorisation Status
Authorised
Combination Treatment
Yes

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