Atrial Fibrillation
Conditions
Keywords
MAA868, apixaban, atrial fibrillation, anticoagulant, Factor XI, D-dimer, systemic thromboembolic events
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.
Interventions
DRUGMAA868
3 MAA868 doses, single administration, subcutaneous,
DRUGApixaban
Apixaban 5 mg b.i.d
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Masking description
blinded (with majuscule) endpoint evaluation
Intervention model description
This is a randomized, open-label, blinded endpoint evaluation, active controlled, dose-range finding study.
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| number of patients achieving FXI inhibition ≥ 80% at trough after monthly dosing at 3 dose levels of MAA868 inhibition | month 3 | Occurrence of achieving ≥ 80% inhibition of FXI (\< 20% free FXI) following 3 months of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| number of patients achieving FXI inhibition ≥ 80% at trough after the first and second dose at 3 dose levels of MAA868 | Month 1 and 2 | Occurrence of achieving ≥ 80% inhibition of FXI (\< 20% free FXI) at trough on Month 1 and Month 2 |
| Number of patients with incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. | day 1 to day 91 | Incidence of major or clinically relevant non-major bleeding events |
| the effect of MAA868 on D dimer and other thrombogenesis biomarkers as indicators of efficacy compared to compotator | Days 31, 61 and 91 | 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). |
Outcome results
None listed