Efficacy and Safety of MAA868 in Patients With Atrial Fibrillation

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

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

Study Overview

• Status: Withdrawn
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: MAA868; Drug: Apixaban

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): October 16, 2018
• Primary Completion (Anticipated): November 28, 2019
• Study Completion (Anticipated): January 30, 2020

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 8, 2018
• First Posted (Actual): January 12, 2018

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: atrial fibrillation; anticoagulant; D-dimer; apixaban; Factor XI; MAA868; systemic thromboembolic events
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban
• Other Study ID Numbers: CMAA868A2202; 2017-002741-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No