Abelacimab versus Dalteparin in the treatment of gastrointestinal (GI)/urogenital (GU) cancer and associated venous thromboembolisms (VTE)

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

ID di studio ICTRP
EUCTR2021-003085-12 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
Eine multizentrische, randomisierte, offene Phase-III-Studie, mit verblindeter Auswertung der Zielparameter, die die Wirkung von Abelacimab im Verhältnis zu Dalteparin auf wiederkehrende venöse Thromboembolien (VTE) und Blutungen bei Patienten mit gastrointestinalem (GI)/urogenitalem (GU) Karzinom im Zusammenhang mit VTE vergleicht (Magnolia) (BASEC)

Titolo accademico
A multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 study comparing 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 (ICTRP)

Titolo pubblico
Abelacimab versus dalteparin in the treatment of GI/GU cancer and associated VTE (ICTRP)

Malattie studiate
venous thromboembolism (VTE) in patients with gastrointestinal/genitourinary cancer;Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14] (ICTRP)

Intervento studiato

Product Name: Abelacimab
Product Code: MAA868
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: ABELACIMAB
Current Sponsor code: MAA868
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-

Trade Name: Fragmin
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Dalteparin sodium
Other descriptive name: DALTEPARIN SODIUM
Concentration unit: IU/kg international unit(s)/kilogram
Concentration type: up to
Concentration number: 18000-

(ICTRP)

Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)

Disegno dello studio
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2 (ICTRP)

Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes

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:
o Unresectable, locally advanced, metastatic, or non-metastatic GI/GU cancer and
o No intended curative surgery during the study
? Confirmed symptomatic or incidental proximal lower limb DVT (i.e., popliteal, femoral, iliac, and/or inferior vena cava vein thrombosis) and/or a confirmed symptomatic 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


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 510
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 510
(ICTRP)

Exclusion criteria:
? Thrombectomy, insertion of a caval filter or use of a fibrinolytic agent to treat the current (index) 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 that for VTE treatment prior to randomization (e.g., AF, mechanical heart valve, prior VTE)
? PE leading to hemodynamic instability (blood pressure [BP] <90 mmHg or shock)
? Acute ischemic or hemorrhagic stroke or intracranial hemorrhage within 4 weeks of screening
? Brain trauma or a cerebral or 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 >100 mg/day or any other antiplatelet agent alone or in combination with aspirin
? Bleeding requiring medical attention at the time of randomization or within 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 <3 months at randomization
? Calculated creatinine clearance (CrCl) <30 mL/min (Cockcroft-Gault equation) 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 (ALT) =3 x and/or bilirubin =2 x upper limit of normal (ULN) at the screening visit in absence of clinical explanation
? Uncontrolled hypertension (systolic 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 (See Section 5.3.6 for highly effective contraceptive measures)
? 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 Investigator?s judgement 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 PD effect has returned to baseline, whichever is longer. Participation in academic non-interventional studies or interventional studies testing different strategies or different combinations of registered drugs is permitted.


Endpoint primari e secondari
Main Objective: The primary objective of this study is to assess whether abelacimab is non-inferior to dalteparin for preventing VTE recurrence through 6 months post randomization in patients with GI or GU cancer and recently diagnosed VTE. If non-inferiority is demonstrated, then superiority will be assessed.;Secondary Objective: 1. To assess whether abelacimab is superior to dalteparin for preventing occurrence of the composite of major or CRNM bleeding
2. To assess whether abelacimab is superior to dalteparin on net clinical benefit defined as survival without VTE recurrence, or major or CRNM bleeding events
3. To assess whether abelacimab is superior to dalteparin on the rate of permanent treatment discontinuation not due to death
4. To assess whether abelacimab is superior to dalteparin for preventing occurrence of CRNM bleeding events
5. To assess whether abelacimab is superior to dalteparin for preventing occurrence of major bleeding events
6. To assess whether abelacimab is superior to dalteparin for preventing occurrence of the composite of GI major and CRNM bleeding
7. To evaluate safety and tolerability of abelacimab relative to dalteparin and to assess the incidence rate of injection site reactions, hypersensitivity reactions and immunogenicity in patients treated with abelacimab
;Primary end point(s): Time to first event of centrally adjudicated VTE recurrence;Timepoint(s) of evaluation of this end point: 6 months post randomization (ICTRP)

Secondary end point(s): 1. Time to first event of ISTH-adjudicated major or CRNM bleeding events
2. Time to first event of VTE recurrence, ISTH-adjudicated major or ISTH-adjudicated CRNM bleeding events
3. Time to event of permanent treatment discontinuation not due to death
4. Time to first event of ISTH-adjudicated CRNM bleeding events
5. Time to first event of ISTH-adjudicated major bleeding events
6. Time to first event of GI ISTH-adjudicated major and GI CRNM bleeding events
7. All-cause death, vascular death, serious adverse events, adverse events leading to drug discontinuation, other adverse events, abnormal lab tests, etc. presented as rate per 100 patient-years
?For patients treated with abelacimab:
oPercentage of patients with injection site reactions
oPercentage of patients with injection site reactions by severity status
oPercentage of patients with hypersensitivity reactions
oPercentage of patients with hypersensitivity reactions by severity status
oPercentage of patients with ADA formation
oPercentage of patients with persistent ADA formation
oPercentage of patients with neutralizing antibody (NAb) formation.
;Timepoint(s) of evaluation of this end point: 6 months post randomization (ICTRP)

Data di registrazione
05.04.2022 (ICTRP)

Inclusione del primo partecipante
25.10.2022 (ICTRP)

Sponsor secondari
non disponibile

Contatti aggiuntivi
Information Desk, info@anthostherapeutics.com, +1617430-6940, Anthos Therapeutics (ICTRP)

ID secondari
ANT-008, 2021-003085-12-LV (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-003085-12 (ICTRP)