A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE

Pulmonary Embolism Clinical Trial

— MAGNOLIA  

Official title:

A Multicenter, Randomized, Open-label, Blinded Endpoint Evaluation, Phase 3 Study Comparing the Effect of Abelacimab vs. Dalteparin on Venous Thromboembolism (VTE) Recurrence and Bleeding in Patients With GI/GU Associated VTE

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05171075
• Other study ID #: ANT-008
• Secondary ID: 2021-003085-12
• Status: Recruiting
• Phase: Phase 3
• Start date: September 27, 2022
• Est. completion date: September 2025

Study information

• Verified date: January 2024
• Source: Anthos Therapeutics, Inc.
• Contact: Nancy Widener
• Phone: 239-284-3741
• Email: Nancy.w[@]anthostherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3, multicenter, open-label, blinded endpoint study to evaluate the effect of abelacimab relative to dalteparin on venous thromboembolism (VTE) recurrence and bleeding in patients with gastrointestinal (GI)/genitourinary (GU) cancer associated VTE (Magnolia)

Description:

Cancer associated thrombosis (CAT) is a severe medical condition which is characterized by high incidence of Venous thromboembolism (VTE) recurrence and high risk for bleeding. Patients with intact GI and GU cancer have increased bleeding risk with oral direct anticoagulants (DOACs), Guidelines advice caution with those DOACs or state preference for low molecular weight heparin (LMWH) in this population. The ANT-008 study will compare treatment with abelacimab monthly administration to LMWH daily subcutaneous (sc) administration over 6-month treatment. The study outcomes include VTE recurrence, bleeding event and treatment discontinuation at 6 months

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1020
• Est. completion date: September 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female subjects =18 years old or other legal maturity age according to the country of residence
• Confirmed GI (colorectal, pancreatic, gastric, esophageal, gastro-esophageal junction or hepatobiliary) or confirmed GU (renal, ureteral, bladder, prostate, or urethra)

cancers if:

• Unresectable, locally advanced, metastatic, or non-metastatic GI/GU cancer and
• No intended curative surgery during the study
• Confirmed symptomatic or incidental proximal lower limb deep vein thrombosis (DVT) (i.e., popliteal, femoral, iliac, and/or inferior vena cava vein thrombosis) and/or a confirmed symptomatic pulmonary embolism (PE), or an incidental PE in a segmental, or larger pulmonary artery. Patients are eligible within 120 hours from diagnosis of the qualifying VTE.
• Anticoagulation therapy with LMWH for at least 6 months is indicated
• Able to provide written informed consent

Exclusion Criteria:

• Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current (index) occurrence of DVT and/or PE
• More than 120 hours of pre-treatment with therapeutic doses of UFH, LMWH, or other anticoagulants
• An indication to continue treatment with therapeutic doses of an anticoagulant other than for VTE treatment prior to randomization (e.g., atrial fibrillation, mechanical heart valve, prior VTE)
• PE leading to hemodynamic instability (systolic BP <90 mmHg or shock).
• Acute ischemic or hemorrhagic stroke or intracranial hemorrhage, in the last 4 weeks preceding screening.
• Brain trauma, or cerebral or a spinal cord surgery or spinal procedures such as lumbar puncture or epidural/spinal anesthesia within 4 weeks of screening
• Need for aspirin in a dosage of more than 100 mg/day or, any other antiplatelet agent alone or in combination with aspirin
• Bleeding requiring medical attention at the time of randomization or in the preceding 4 weeks
• Planned brain, spinal cord, cardiac, vascular, major thoracic and/or major abdominal surgery in the 4 weeks following randomization
• History of heparin induced thrombocytopenia
• Infective acute or subacute endocarditis at the time of presentation
• Primary brain cancer or untreated intracranial metastasis
• Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening
• Life expectancy of <3 months at randomization
• Calculated creatinine clearance (CrCl) <30 mL/min at the screening visit
• Platelet count <50,000/ mm3 at the screening visit
• Hemoglobin <8 g/dL at the screening visit
• Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase =3 times and/or bilirubin =2 times the upper limit of normal (ULN) at the screening visit in the absence of clinical explanation
• Uncontrolled hypertension (systolic blood pressure [BP] > 180 mm Hg or diastolic BP >100 mm Hg despite antihypertensive treatment)
• Women of child-bearing potential (WOCBP) who are unwilling or unable to use highly effective contraceptive measures during the study from screening up to 3 days after last treatment of dalteparin or 100 days after administration of abelacimab
• Sexually active males with sexual partners of childbearing potential must agree to use a condom or other reliable contraceptive measure up to 3 days after last treatment of dalteparin or 100 days after administration of abelacimab
• Pregnant or breast-feeding women
• History of hypersensitivity to any of the study drugs (including dalteparin) or its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for dalteparin
• Subjects with any condition that in the judgement of the Investigator would place the subject at increased risk of harm if he/she participated in the study
• Use of other investigational (not-registered) drugs within 5 half-lives prior to enrollment or until the expected pharmacodynamic effect has returned to baseline, whichever is longer. Participation in academic non-interventional studies or interventional studies, comprising testing different strategies or different combinations of registered drugs is permitted.

Related Conditions & MeSH terms

• Deep Venous Thrombosis
• Embolism
• Pulmonary Embolism
• Thromboembolism
• Thrombosis
• Venous Thromboembolism
• Venous Thrombosis

Intervention

Biological:
• Abelacimab
Abelacimab 150 mg

Drug:
• Dalteparin
Dalteparin 200 IU/kg/day followed by 150 IU/kg/day

Locations

Country	Name	City	State
Australia	Blacktown Hospital	Blacktown	New South Wales
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Concord Repatriation General Hospital	Concord
Australia	Northern Health	Epping	Victoria
Australia	Perth Blood Institute	Perth
Australia	The Alfred Hospital	Prahran
Australia	Westmead Hospital	Westmead	New South Wales
Austria	LKH - Universitätsklinikum Graz	Graz
Austria	LK Wiener Neustadt	Neustadt
Austria	Medical University of Vienna	Vienna
Canada	University of Calgary	Calgary
Canada	Hamilton Health Sciences, Juravinski Hospital and Cancer Centre	Hamilton	Ontario
Canada	Sault Area Hospital	Marie
Canada	Jewish General Hospital	Montréal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Ottawa Hospital Research Instituite	Ottawa	Ontario
Canada	Ottawa Hospital Research Instituite	Ottawa	Ontario
Canada	Niagara Health System	Saint Catharines	Ontario
Canada	Toronto General Hospital	Toronto
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	University Hospital Hradec Kralove	Hradec Králové
Czechia	Nemocnice Na Pleši s.r.o.	Nová Ves Pod Pleší
Czechia	Onkologická klinika VFN a 1. LF UK	Prague
Czechia	Thomayerova nemocnice	Praha
France	CHU Amiens - Hopital Nord	Amiens
France	CHU Angers - Hôpital Hôtel Dieu	Angers
France	CHU de Brest - Hôpital de la Cavale Blanche	Brest	Cedex
France	CHU Clermont Ferrand - Hopital Gabriel Montpied	Clermont-Ferrand
France	Hôpital Louis Mourier	Colombes	Renouiflers
France	CHU Dijon - Hôpital Bocage Central	Dijon
France	CHU de Grenoble - Hôpital Albert Michallon	Grenoble
France	CH Le Puy en Velay	Le Puy-en-Velay	Chantemesse
France	CHU de Limoges - Hôpital Dupuytren	Limoges
France	CHU de Limoges - Hôpital Dupuytren	Limoges	Cedex
France	Hopital Timone Adultes	Marseille
France	Groupe Hospitalier Pitie-Salpetriere	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud	Pierre-Bénite
France	CHU de Rouen - Hôpital de Bois Guillaume	Rouen
France	CHU de Saint-Etienne - Hopital Nord	Saint-Étienne
France	CHU Strasbourg - Nouvel Hôpital Civil	Strasbourg
France	Nouvel Hôpital Civil de Strasbourg	Strasbourg
France	Centre Hospitalier Intercommunal de Toulon	Toulon
France	CHU de Nancy - Hôpital de Brabois Adultes	Vandœuvre-lès-Nancy
France	CHU de Nancy - Hôpital de Brabois Adultes	Vandœuvre-lès-Nancy	Rue Du Morvan
Germany	Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt	Dresden
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Praxis für Gefäßmedizin	Görlitz
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinik der Christian-Albrechts-Universität	Kiel
Germany	Universitätsklinik Leipzig	Leipzig
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Debreceni Egyetem	Debrecen
Hungary	Markhot Ferenc Oktatokorhaz es Rendelointezet	Eger
Hungary	Bacs-Kiskun County Hospital	Kecskemét
Hungary	University of Pécs	Pécs
Ireland	Bon Secour Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	University Hospital, Limerick	Limerick
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII	Bergamo
Italy	Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia	Bologna
Italy	Presidio Ospedaliero di Castelfranco Veneto	Castelfranco Veneto
Italy	SS. ma Annunziata	Chieti
Italy	Ospedale Civile Dell Annunziata	Cosenza
Italy	Ospedale Degli Infermi	Faenza
Italy	Azienda Ospedaliero Universitaria San Martino	Genova
Italy	Presidio Ospedaliero della Misericordia	Grosseto
Italy	Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo	Milano
Italy	A.O.U. Policlinico di Modena	Modena
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Azienda Ospedale - Università Padova	Padova
Italy	Ospedale Universitario	Padova
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Universit degli Studi di Perugia - Azienda Ospedaliera di Perugia	Perugia
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia	Reggio Emilia
Italy	Fondazione Policlinico Universitario A. Gemelli IRCCS.	Roma
Italy	Istituto Clinico Humanitas	Rozzano
Italy	Ospedale Santa Maria di Cà Foncello	Treviso
Italy	Azienda Ospedaliero-Universitaria Santa Maria della Misericordia	Udine
Italy	Università dell'Insubria	Varese
Italy	Ospedale SS. Giovanni e Paolo	Venezia
Italy	Ospedalemichele e Pietro ferrer	Verduno
Italy	Ospedale San Bortolo di Vicenza	Vicenza
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang-Si
Korea, Republic of	SoonChunHyang University Hospital Bucheon	Bucheon
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Daegu Catholic University Medical Center	Daegu
Korea, Republic of	Yongin Severance Hospital, Yonsei University Health System	Gyeonggi-do
Korea, Republic of	Jeonbuk National University Hospital	Jeonju
Korea, Republic of	Myongji Hospital	Jeonju
Korea, Republic of	Dong-A University Hospital	Pusan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital at Gangdong	Seoul
Korea, Republic of	Soonchunhyang University Seoul Hospital	Seoul
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	Liepaja Regional Hospital	Liepaja
Latvia	Pauls Stradins CUH	Riga
Latvia	Riga East University Hospital	Riga
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Onze Lieve Vrouwe Gasthuis, Locatie Oost	Amsterdam
Netherlands	Rode Kruis Ziekenhuis	Beverwijk
Netherlands	Haga Ziekenhuis	Den Haag
Netherlands	Albert Schweitzer Ziekenhuis, Dordwijk	Dordrecht
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Spaarne Gasthuis (Kennemer Gasthuis) - Haarlem-Zuid	Haarlem
Netherlands	Tergooiziekenhuizen, Hilversum	Hilversum
Netherlands	Amsterdam University Medical Center	Holland
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen
Netherlands	Ikazia Ziekenhuis	Rotterdam
Norway	Østfold Hospital Kalnes	Fredrikstad
Norway	Akershus Univeristy Hospital	Lørenskog
Norway	Oslo University Hospital	Oslo
Spain	Hospital Universitario Del Vinalopo	Alicante
Spain	Complejo Hospital Vall D'Hebron	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu I Sant Pau	Barcelona
Spain	Hospital Universitario Reina Sofia	Córdoba
Spain	Hospital General Universitario de Elche	Elche
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Universitario Ciudad de Jaen	Jaén
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	MD Anderson Cancer Centre	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda
Spain	Complejo Hospitalario Universitario de Ourense	Ourense
Spain	Hospital Universitario Central de Asturia	Oviedo
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Corporacio Sanitaria Parc Tauli	Sabadell
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Complejo Hospitalario Universitario de Santiago	Santiago De Compostela
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Sweden	Länssjukhuset Sundsvall-Härnösand	Sundsvall
Switzerland	Hopital Universitaire Geneve	Geneve
Switzerland	University of Zürich	Zürich
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Far Eastern Memorial Hospital	New Taipei City
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University (NCKU) Hospital	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	Tri-Service General Hospital	Taipei
United Kingdom	University Hospital of Wales	Cardiff	England
United Kingdom	Castle Hill Hospital, Department of Oncology & Haematology	Cottingham	ENG
United Kingdom	Queen Elizabeth University Hospital Campus	Glasgow	SCO
United Kingdom	Barts Health NHS Trust	London	England
United Kingdom	The Newcastle Upon Tyne Hospitals	Newcastle Upon Tyne	ENG
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	NorthShore University Health System	Evanston	Illinois
United States	University of Miami Health System/Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Temple University	Philadelphia	Pennsylvania
United States	University of Pennsylvania - Penn Blood Disorders Center	Philadelphia	Pennsylvania
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	University of Texas Mays Cancer Center	San Antonio	Texas
United States	Washington DC VAMC	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Anthos Therapeutics, Inc.	Itreas

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Czechia,  France,  Germany,  Hungary,  Ireland,  Italy,  Korea, Republic of,  Latvia,  Netherlands,  Norway,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first event of centrally adjudicated VTE recurrence consisting of new proximal deep venous thrombosis, new pulmonary embolism (PE) or fatal PE, including unexplained death for which PE cannot be ruled out		6 months
Secondary	Time to first event of ISTH-adjudicated major or clinically relevant non-major (CRNM) bleeding events		6 months
Secondary	Net clinical benefit defined as survival without VTE recurrence, or major or CRNM bleeding		6 months