Efficacy and Safety of MAA868 in Patients With Atrial Fibrillation

NCT03398434 | Withdrawn Phase 2 DMC

• 2 other identifiers: CMAA868A22022017-002741-29
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Atrial Fibrillation

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

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

  day 1 to day 91

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

  Days 31, 61 and 91

Study Arms (4)

MAA868 low dose regimen

EXPERIMENTAL

patients receive dose monthly.

Drug: MAA868

MAA868 middle dose regimen

EXPERIMENTAL

patients receive dose monthly.

Drug: MAA868

MAA868 high dose regimen

EXPERIMENTAL

patients receive dose monthly.

Drug: MAA868

Apixaban

ACTIVE COMPARATOR

Apixaban 5 mg b.i.d

Drug: Apixaban

Interventions

MAA868 DRUG

3 MAA868 doses, single administration, subcutaneous,

MAA868 high dose regimen; MAA868 low dose regimen; MAA868 middle dose regimen

Apixaban DRUG

Apixaban 5 mg b.i.d

Apixaban

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

MAA868; apixaban

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: blinded (with majuscule) endpoint evaluation
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: January 12, 2018
• Study Start: October 16, 2018
• Primary Completion: November 28, 2019
• Study Completion: January 30, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share