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

NCT04213807 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ANT-004
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Atrial Fibrillation

Keywords

atrial fibrillation; flutter; paroxysmal atrial fibrillation; stroke; cardiac arrhythmia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

  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

  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

  Day 1 through end of study, up to 170 days

• Immunogenicity of MAA868

  Days 1, 31, 61, 71, 91, 121 and 170

Study Arms (2)

MAA868

EXPERIMENTAL

Subcutaneous injection on Day 1 with two subsequent monthly injections

Biological: MAA868 Cohort 1; Biological: MAA868 Cohort 2; Biological: MAA868 Cohort 3

Placebo

PLACEBO COMPARATOR

Subcutaneous injection: Placebo on Day 1 with two subsequent monthly injections

Other: Placebo

Interventions

MAA868 Cohort 1 BIOLOGICAL

Subcutaneous injection: low dose

MAA868

MAA868 Cohort 2 BIOLOGICAL

Subcutaneous injection: high dose

MAA868

MAA868 Cohort 3 BIOLOGICAL

Subcutaneous injection: Dose to be determined.

MAA868

Placebo OTHER

Subcutaneous injection: Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

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. (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

Sponsors & Collaborators

• Anthos Therapeutics, Inc.: lead
• Covance: collaborator

Study Sites (6)

Anthos Investigative Site

Beverly Hills, California, 90211, United States

Location

Anthos Investigative Site

Wichita, Kansas, 67207, United States

Location

Anthos Investigative Site

Alexandria, Louisiana, 71301, United States

Location

Anthos Investigative Site

Lansing, Michigan, 48912, United States

Location

Anthos Investigative Site

Wynnewood, Pennsylvania, 19096, United States

Location

Anthos Investigative Site

McKinney, Texas, 75069, United States

Location

MeSH Terms

Conditions

Atrial Fibrillation; Stroke; Arrhythmias, Cardiac

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Results Point of Contact

• Title: Debra Freedholm
• Organization: Anthos Therapeutics

Deb.f@anthostherapeutics.com

609-439-8246

Study Officials

• Norman E Lepor, MD FACC FAHA FSCAI

  Westside Medical Associates of Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2019
• First Posted: December 30, 2019
• Study Start: December 11, 2019
• Primary Completion: December 29, 2020
• Study Completion: March 8, 2021
• Last Updated: January 11, 2022
• Results First Posted: December 7, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)