Efficacy and Safety of MAA868 in Patients With Atrial Fibrillation

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

Official Title
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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

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: MAA868
* Drug: Apixaban


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, open-label, blinded endpoint evaluation, active controlled, dose-range finding study.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAA868 low dose regimen<br>patients receive dose monthly. | Drug: MAA868<br>* 3 MAA868 doses, single administration, subcutaneous,<br>|
| Experimental: MAA868 middle dose regimen<br>patients receive dose monthly. | Drug: MAA868<br>* 3 MAA868 doses, single administration, subcutaneous,<br>|
| Experimental: MAA868 high dose regimen<br>patients receive dose monthly. | Drug: MAA868<br>* 3 MAA868 doses, single administration, subcutaneous,<br>|
| Active Comparator: Apixaban<br>Apixaban 5 mg b.i.d | Drug: Apixaban<br>* Apixaban 5 mg b.i.d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients achieving FXI inhibition ≥ 80% at trough after monthly dosing at 3 dose levels of MAA868 inhibition | Occurrence of achieving ≥ 80% inhibition of FXI (< 20% free FXI) following 3 months of treatment. | month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients achieving FXI inhibition ≥ 80% at trough after the first and second dose at 3 dose levels of MAA868 | Occurrence of achieving ≥ 80% inhibition of FXI (< 20% free FXI) at trough on Month 1 and Month 2 | Month 1 and 2 | 
| Number of patients with incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. | Incidence of major or clinically relevant non-major bleeding events | day 1 to day 91 | 
| the effect of MAA868 on D dimer and other thrombogenesis biomarkers as indicators of efficacy compared to compotator | Change from baseline to Day 31, Day 61 and Day 91 in thrombogenesis biomarkers (D-dimer, prothrombin fragment 1.2 (F1.2), thrombin-antithrombin III-complexes (TAT), fibrinogen). | Days 31, 61 and 91 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MAA868, apixaban, atrial fibrillation, anticoagulant, Factor XI, D-dimer, systemic thromboembolic events