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Efficacy and Safety of MAA868 in Patients With Atrial Fibrillation

Primary Purpose

Atrial Fibrillation

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

MAA868

Apixaban

About this trial

This is an interventional basic science trial for Atrial Fibrillation focused on measuring MAA868, apixaban, atrial fibrillation, anticoagulant, Factor XI, D-dimer, systemic thromboembolic events

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

MAA868 low dose regimen

MAA868 middle dose regimen

MAA868 high dose regimen

Apixaban

Arm Description

patients receive dose monthly.

Apixaban 5 mg b.i.d

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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

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).

Full Information

NCT ID

NCT03398434

First Posted

January 8, 2018

Last Updated

October 5, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03398434

Brief Title

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

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Trial cancelled before First Patient First Visit (no patient enrolled)

Study Start Date

October 16, 2018 (Anticipated)

Primary Completion Date

November 28, 2019 (Anticipated)

Study Completion Date

January 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atrial Fibrillation

Keywords

MAA868, apixaban, atrial fibrillation, anticoagulant, Factor XI, D-dimer, systemic thromboembolic events

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

Outcomes Assessor

Masking Description

blinded (with majuscule) endpoint evaluation

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MAA868 low dose regimen

Arm Type

Experimental

Arm Description

patients receive dose monthly.

Arm Title

MAA868 middle dose regimen

Arm Type

Experimental

Arm Description

patients receive dose monthly.

Arm Title

MAA868 high dose regimen

Arm Type

Experimental

Arm Description

patients receive dose monthly.

Arm Title

Apixaban

Arm Type

Active Comparator

Arm Description

Apixaban 5 mg b.i.d

Intervention Type

Drug

Intervention Name(s)

MAA868

Intervention Description

3 MAA868 doses, single administration, subcutaneous,

Intervention Type

Drug

Intervention Name(s)

Apixaban

Intervention Description

Apixaban 5 mg b.i.d

Primary Outcome Measure Information:

Title

number of patients achieving FXI inhibition ≥ 80% at trough after monthly dosing at 3 dose levels of MAA868 inhibition

Description

Occurrence of achieving ≥ 80% inhibition of FXI (< 20% free FXI) following 3 months of treatment.

Time Frame

month 3

Secondary Outcome Measure Information:

Title

number of patients achieving FXI inhibition ≥ 80% at trough after the first and second dose at 3 dose levels of MAA868

Description

Occurrence of achieving ≥ 80% inhibition of FXI (< 20% free FXI) at trough on Month 1 and Month 2

Time Frame

Month 1 and 2

Title

Number of patients with incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period.

Description

Incidence of major or clinically relevant non-major bleeding events

Time Frame

day 1 to day 91

Title

the effect of MAA868 on D dimer and other thrombogenesis biomarkers as indicators of efficacy compared to compotator

Description

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).

Time Frame

Days 31, 61 and 91

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

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

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Learn more about this trial

Efficacy and Safety of MAA868 in Patients With Atrial Fibrillation

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