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

Primary Purpose

Atrial Fibrillation

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

MAA868 Cohort 1

MAA868 Cohort 2

MAA868 Cohort 3

Placebo

About this trial

This is an interventional prevention trial for Atrial Fibrillation focused on measuring atrial fibrillation, flutter, paroxysmal atrial fibrillation, stroke, cardiac arrhythmia

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Anthos Investigative Site
Anthos Investigative Site
Anthos Investigative Site
Anthos Investigative Site
Anthos Investigative Site
Anthos Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

MAA868

Placebo

Arm Description

Subcutaneous injection on Day 1 with two subsequent monthly injections

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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.

Full Information

NCT ID

NCT04213807

First Posted

December 23, 2019

Last Updated

December 24, 2021

Sponsor

Anthos Therapeutics, Inc.

Collaborators

Covance

1. Study Identification

Unique Protocol Identification Number

NCT04213807

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

December 11, 2019 (Actual)

Primary Completion Date

December 29, 2020 (Actual)

Study Completion Date

March 8, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Anthos Therapeutics, Inc.

Collaborators

Covance

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

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

Atrial Fibrillation

Keywords

atrial fibrillation, flutter, paroxysmal atrial fibrillation, stroke, cardiac arrhythmia

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MAA868

Arm Type

Experimental

Arm Description

Subcutaneous injection on Day 1 with two subsequent monthly injections

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

MAA868 Cohort 1

Intervention Description

Subcutaneous injection: low dose

Intervention Type

Biological

Intervention Name(s)

MAA868 Cohort 2

Intervention Description

Subcutaneous injection: high dose

Intervention Type

Biological

Intervention Name(s)

MAA868 Cohort 3

Intervention Description

Subcutaneous injection: Dose to be determined.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Subcutaneous injection: Placebo

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Day 91

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Day 31 and Day 61

Title

Overall Number of Participants Who Experienced Adverse Events, Including Serious Adverse Events, During the Treatment Period and Through End of Study

Description

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

Time Frame

Day 1 through end of study, up to 170 days

Title

Incidence of Major Bleeding Events, Clinically Relevant Non-major Bleeding Events and Total Bleeding With MAA868 Relative to Placebo

Description

Occurrence of confirmed major bleeding events, clinically relevant non-major bleeding events and total bleeding events during the treatment period

Time Frame

Day 1 through end of study, up to 170 days

Title

Immunogenicity of MAA868

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Norman E Lepor, MD FACC FAHA FSCAI

Organizational Affiliation

Westside Medical Associates of Los Angeles

Official's Role

Principal Investigator

Facility Information:

Facility Name

Anthos Investigative Site

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211

Country

United States

Facility Name

Anthos Investigative Site

City

Wichita

State/Province

Kansas

ZIP/Postal Code

67207

Country

United States

Facility Name

Anthos Investigative Site

City

Alexandria

State/Province

Louisiana

ZIP/Postal Code

71301

Country

United States

Facility Name

Anthos Investigative Site

City

Lansing

State/Province

Michigan

ZIP/Postal Code

48912

Country

United States

Facility Name

Anthos Investigative Site

City

Wynnewood

State/Province

Pennsylvania

ZIP/Postal Code

19096

Country

United States

Facility Name

Anthos Investigative Site

City

McKinney

State/Province

Texas

ZIP/Postal Code

75069

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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