A Dose-range Finding Study of MAA868 in Patients With Atrial Fibrillation

A Randomized, Placebo-controlled, Dose-range Finding Study to Assess the Pharmacokinetic and Pharmacodynamic Parameters, Safety, Tolerability, and Immunogenicity of MAA868 in Patients With Atrial Fibrillation

This study is a multicenter, randomized, subject and Investigator-blinded, placebo-controlled, parallel-group, multiple ascending dose-ranging study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) effects of MAA868 in patients with atrial fibrillation (AF) or flutter at low risk of thromboembolic stroke or peripheral embolism.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Biological: MAA868 Cohort 1; Biological: MAA868 Cohort 2; Biological: MAA868 Cohort 3; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Anthos Investigative Site
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Anthos Investigative Site
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Anthos Investigative Site
  • Michigan
    • Lansing, Michigan, United States, 48912
      • Anthos Investigative Site
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Anthos Investigative Site
  • Texas
    • McKinney, Texas, United States, 75069
      • Anthos Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients ≥ 18 and < 85 years old with paroxysmal atrial fibrillation (PAF) or atrial flutter on 12 lead electrocardiography at Screening Or
• Patients with a history of PAF or atrial flutter, as documented by (telemetry, 12 lead electrocardiography or ambulatory [e.g. Holter] monitor) and not due to a reversible condition (e.g. alcohol binge drinking) can be entered even if they do not have PAF at Screening. There is not time-limit for this.
• Patients with a Congestive heart failure, Hypertension, Age ( > 65 = 1 point, > 75 = 2 points), Diabetes, previous Stroke/transient ischemic attack (2 points) (CHA2DS2-VASc) risk score (tool as a predictor for estimating the risk of stroke in patients with atrial fibrillation (AF); Lip et al 2010) of 0-1 for men and 1-2 for women and in whom, in the investigator's judgment, the use of an anticoagulant for stroke prevention is not indicated

Exclusion Criteria:

• History of stroke, transient ischemic attack or systemic embolism
• History of major bleeding during treatment with an anticoagulant or antiplatelet therapy. (Patients who have had major bleeding on anticoagulants or antiplatelet therapy more than a year ago can be enrolled only if the bleeding was due to a reversible cause, e.g. gastro-duodenal ulcer that was successfully treated.)
• History of traumatic or non-traumatic intracranial, intraspinal or intraocular 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 clinically significant valvular heart disease including moderate or severe mitral stenosis (valve area <1.5 cm2)
• Patients with a prosthetic heart valve

Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MAA868; Subcutaneous injection on Day 1 with two subsequent monthly injections	Biological: MAA868 Cohort 1; Subcutaneous injection: low dose; Biological: MAA868 Cohort 2; Subcutaneous injection: high dose; Biological: MAA868 Cohort 3; Subcutaneous injection: Dose to be determined.
PLACEBO_COMPARATOR: Placebo; Subcutaneous injection: Placebo on Day 1 with two subsequent monthly injections	Other: Placebo; Subcutaneous injection: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Achieved More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After the Third Dose (Day 91) at Different Dose Levels of MAA868	Number of participants achieving more than or equal to 50%, 80%, and 90% inhibition of factor XI (less than 50%, 20%, or 10% free factor XI) at trough after the third dose on Day 91 at different dose levels of MAA868	Day 91

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving More Than or Equal to 50%, 80%, and 90% Factor XI Inhibition at Trough After First (Day 31) and Second Doses (Day 61) at Different Dose Levels of MAA868	Number of participants achieving more than or equal to 50%, 80%, and 90% inhibition of factor XI (less than 50%, 20%, or 10% free factor XI) at trough on Day 31 (after first dose) and Day 61 (after second dose) at different dose levels of MAA868	Day 31 and Day 61
Overall Number of Participants Who Experienced Adverse Events, Including Serious Adverse Events, During the Treatment Period and Through End of Study	Overall number of participants who experienced adverse events following multiple subcutaneous administration of MAA868 compared to placebo in participants with atrial fibrillation or atrial flutter	Day 1 through end of study, up to 170 days
Incidence of Major Bleeding Events, Clinically Relevant Non-major Bleeding Events and Total Bleeding With MAA868 Relative to Placebo	Occurrence of confirmed major bleeding events, clinically relevant non-major bleeding events and total bleeding events during the treatment period	Day 1 through end of study, up to 170 days
Immunogenicity of MAA868	Number of participants with anti-drug (MAA868) antibodies for all participants who received MAA868 120 mg or MAA868 180 mg. "Non-evaluable observation" refers to participants who had no sample collected (due to no visit or remote visit) or for whom the sample was not frozen.	Days 1, 31, 61, 71, 91, 121 and 170

Collaborators and Investigators

• Sponsor: Anthos Therapeutics, Inc.
• Collaborators: Covance
• Investigators: Principal Investigator: Norman E Lepor, MD FACC FAHA FSCAI, Westside Medical Associates of Los Angeles

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 11, 2019
• Primary Completion (ACTUAL): December 29, 2020
• Study Completion (ACTUAL): March 8, 2021

Study Registration Dates

• First Submitted: December 23, 2019
• First Submitted That Met QC Criteria: December 26, 2019
• First Posted (ACTUAL): December 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 24, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: stroke; atrial fibrillation; paroxysmal atrial fibrillation; cardiac arrhythmia; flutter
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: ANT-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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