Clinical trial NCT03398434: Efficacy and Safety of MAA868 in Patients With Atrial Fibrillation
Official title: A Multicenter, Randomized, Open-label, Active-controlled, Dose-range Finding Study to Assess the Pharmacodynamic Parameters, Safety and Tolerability of MAA868 and Its Effect on Thrombogenesis Biomarkers Compared to Apixaban in Patients With Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Atrial Fibrillation
Keywords: MAA868
apixaban
atrial fibrillation
anticoagulant
Factor XI
D-dimer
systemic thromboembolic events
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-01-12
Enrollment: 0
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, open-label, blinded endpoint evaluation, active controlled, dose-range finding study.
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of MAA868 compared to apixaban in patients with atrial fibrillation.


Eligibility criteria: Inclusion Criteria:

* Male and female patients ≥ 55 and \< 85 years old
* Body weight between 50 and 130 kg inclusive
* Atrial fibrillation or atrial flutter, as documented by electrocardiography
* CHA2DS2-VASc risk score ≥ 2 for male and female patients. Male patients with CHA2DS2VASc risk score of 1 can be included if anticoagulation therapy is warranted.
* Either anticoagulant-naïve or receiving a stable treatment of a recommended dose of a new oral anticoagulant (NOAC) over the 8 weeks prior to screening.

Exclusion Criteria:

* History of stroke, transient ischemic attack or systemic embolism
* History of major bleeding during treatment with an anticoagulant or antiplatelet therapy in the last 12 months
* History of traumatic or non-traumatic intracranial, intraspinal or intra-ocular bleeding
* Known bleeding diathesis or any known active bleeding site at screening or baseline
* Family history of bleeding disorder
* Known active GI lesions predisposing to bleeding events
* Myocardial infarction, unstable angina pectoris or coronary artery bypass graft (CABG) surgery within 12 months prior to the screening period
* Known hemodynamically significant valvular heart disease
* Uncontrolled hypertension defined as SBP/DBP ≥ 160/100 mmHg at the screening visit
* Heart failure NYHA class IV in the 3 months prior to the screening visit
* Dual antiplatelet therapy. Treatment with a P2Y12 inhibitor or low dose aspirin (≤ 100 mg/d) is allowed but not both.
* Severe renal impairment (creatinine clearance \< 30 mL/min) at the screening visit

Primary outcomes:
measure: number of patients achieving FXI inhibition ≥ 80% at trough after monthly dosing at 3 dose levels of MAA868 inhibition
timeFrame: month 3
Secondary outcomes:
measure: number of patients achieving FXI inhibition ≥ 80% at trough after the first and second dose at 3 dose levels of MAA868
timeFrame: Month 1 and 2
measure: Number of patients with incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period.
timeFrame: day 1 to day 91
measure: the effect of MAA868 on D dimer and other thrombogenesis biomarkers as indicators of efficacy compared to compotator
timeFrame: Days 31, 61 and 91
Other outcomes:
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