Clinical trial NCT04213807: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
Keywords: atrial fibrillation
flutter
paroxysmal atrial fibrillation
stroke
cardiac arrhythmia
Lead sponsor: Anthos Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Covance
First posted: 2019-12-30
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: 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
timeFrame: Day 91
Secondary outcomes:
measure: 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
timeFrame: Day 31 and Day 61
measure: Overall Number of Participants Who Experienced Adverse Events, Including Serious Adverse Events, During the Treatment Period and Through End of Study
timeFrame: Day 1 through end of study, up to 170 days
measure: Incidence of Major Bleeding Events, Clinically Relevant Non-major Bleeding Events and Total Bleeding With MAA868 Relative to Placebo
timeFrame: Day 1 through end of study, up to 170 days
measure: Immunogenicity of MAA868
timeFrame: Days 1, 31, 61, 71, 91, 121 and 170
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Anthos Investigative Site
state: California
city: Wichita
country: United States
facility: Anthos Investigative Site
state: Kansas
city: Alexandria
country: United States
facility: Anthos Investigative Site
state: Louisiana
city: Lansing
country: United States
facility: Anthos Investigative Site
state: Michigan
city: Wynnewood
country: United States
facility: Anthos Investigative Site
state: Pennsylvania
city: McKinney
country: United States
facility: Anthos Investigative Site
state: Texas
Study officials:
affiliation: Westside Medical Associates of Los Angeles
name: Norman E Lepor, MD FACC FAHA FSCAI
role: PRINCIPAL_INVESTIGATOR
References: