Efficacy and Safety of MAA868 in Patients With Atrial Fibrillation

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT03398434

Collaborator

(none)

Enrollment

Arms

15.5

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: MAA868 Drug: Apixaban	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a randomized, open-label, blinded endpoint evaluation, active controlled, dose-range finding study.This is a randomized, open-label, blinded endpoint evaluation, active controlled, dose-range finding study.

Masking:

Single (Outcomes Assessor)

Masking Description:

blinded (with majuscule) endpoint evaluation

Primary Purpose:

Basic Science

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

Anticipated Study Start Date :

Oct 16, 2018

Anticipated Primary Completion Date :

Nov 28, 2019

Anticipated Study Completion Date :

Jan 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MAA868 low dose regimen patients receive dose monthly.	Drug: MAA868 3 MAA868 doses, single administration, subcutaneous,
Experimental: MAA868 middle dose regimen patients receive dose monthly.	Drug: MAA868 3 MAA868 doses, single administration, subcutaneous,
Experimental: MAA868 high dose regimen patients receive dose monthly.	Drug: MAA868 3 MAA868 doses, single administration, subcutaneous,
Active Comparator: Apixaban Apixaban 5 mg b.i.d	Drug: Apixaban Apixaban 5 mg b.i.d

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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