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Withdrawn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
Sponsored by
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
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
Experimental
Experimental
Active Comparator
Arm Label
MAA868 low dose regimen
MAA868 middle dose regimen
MAA868 high dose regimen
Apixaban
Arm Description
patients receive dose monthly.
patients receive dose monthly.
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
No
Studies a U.S. FDA-regulated Device Product
No
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
No
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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