Safety and Tolerability of Abelacimab (MAA868) vs. Rivaroxaban in Patients With Atrial Fibrillation (AZALEA-TIMI 71)

• ClinicalTrials.gov Identifier: NCT04755283
• Recruitment Status: Active, not recruiting
• First Posted: February 16, 2021
• Last Update Posted: March 18, 2024
• Sponsor: Anthos Therapeutics, Inc.
• Collaborators: The TIMI Study Group; Laboratory Corporation of America
• Information provided by (Responsible Party): Anthos Therapeutics, Inc.

Tracking Information

• First Submitted Date: February 11, 2021
• First Posted Date: February 16, 2021
• Last Update Posted Date: March 18, 2024
• Actual Study Start Date: February 2, 2021
• Actual Primary Completion Date: December 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 11, 2021)

Evaluate effect of abelacimab relative to rivaroxaban on the rate of major or clinically relevant non-major (CRNM) bleeding events [ Time Frame: From randomization through study completion, an average of 17 months ]

Time to first event of composite of International Society on Thrombosis and Haemostasis (ISTH)-defined major bleeding or CRNM bleeding events

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 11, 2021)

• Evaluate effect of abelacimab relative to rivaroxaban on the rate of major bleeding events [ Time Frame: From randomization through study completion, an average of 17 months ]
  Time to first event ISTH-defined major bleeding events
• Evaluate the effect of abelacimab relative to rivaroxaban on the rate of major or minor bleeding events [ Time Frame: From randomization through study completion, an average of 17 months ]
  Time to first event ISTH-defined major or minor bleeding events

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Tolerability of Abelacimab (MAA868) vs. Rivaroxaban in Patients With Atrial Fibrillation
• Official Title: A Multicenter, RandomiZed, Active-ControLled Study to Evaluate the Safety and Tolerability of Two Blinded Doses of Abelacimab (MAA868) Compared With Open-Label Rivaroxaban in Patients With Atrial Fibrillation (AZALEA)
• Brief Summary: The purpose of the ANT-006 study is to evaluate the bleeding profile of abelacimab relative to rivaroxaban in patients with atrial fibrillation (AF) at moderate-to-high risk of stroke.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is an event-driven, randomized, active-controlled, blinded endpoint, parallel-group study to evaluate the effect of two blinded doses of abelacimab relative to open-label rivaroxaban on the rate of major or clinically relevant non-major (CRNM) bleeding events in patients with atrial fibrillation (AF) who are at moderate-to-high risk of stroke.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

All care providers are blinded with the exception of the pharmacist and study team member assigned to administer the subcutaneous injection of abelacimab.

Primary Purpose: Supportive Care

Condition

• Atrial Fibrillation (AF)
• Stroke

Intervention

• Biological: Abelacimab
  Abelacimab provided as liquid in vial (150 mg/mL)
  Other Name: MAA868
• Drug: Rivaroxaban
  Rivaroxaban 15 mg and 20 mg provided as commercially available film-coated tablets

Study Arms

• Experimental: Abelacimab (MAA868)

  Treatment group 1: Abelacimab middle dose subcutaneous (s.c.) monthly

  Treatment group 2: Abelacimab high dose subcutaneous (s.c.) monthly

  Extension Treatment Group: Abelacimab high dose subcutaneous (s.c.) monthly

  Intervention: Biological: Abelacimab
• Active Comparator: Rivaroxaban

  Treatment group 3: Rivaroxaban 20 mg by mouth; orally (p.o.) once per day with the evening meal

  Patients with a Creatinine Clearance (CrCl) ≤50 ml/min by the Cockcroft-Gault equation will have a dose adaptation to rivaroxaban 15 mg p.o. daily.

  Intervention: Drug: Rivaroxaban

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 11, 2021): 1200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2025
• Actual Primary Completion Date: December 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female patients ≥ 55 years old
• Patients with a history of atrial fibrillation (AF) or atrial flutter with planned indefinite anticoagulation

• Patients with a CHA2DS2-VASc of ≥4 OR a CHA2DS2-VASc of ≥3 with at least 1 of the following:

  1. Planned concomitant use of antiplatelet medication use (i.e., aspirin and/or P2Y12 inhibitor) for the duration of the trial
  2. Creatinine Clearance (CrCl) ≤50 ml/min by the Cockcroft-Gault equation

Exclusion Criteria:

• History of hypersensitivity to any of the study drugs (including rivaroxaban) or its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for rivaroxaban
• Patients with an intracranial or intraocular bleed within the 3 months prior to screening
• Clinically significant mitral stenosis (valve area <1.5 cm2)
• Mechanical heart valve or other indication for anticoagulation therapy other than atrial fibrillation (e.g., venous thromboembolism)
• Known presence of an atrial myxoma or left ventricular thrombus
• History of left atrial appendage closure or removal
• Active endocarditis

Other protocol defined Inclusion/Exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, Hungary, Korea, Republic of, Poland, Taiwan, United States

Administrative Information

• NCT Number: NCT04755283
• Other Study ID Numbers: ANT-006; 2020-004507-13 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Anthos Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Anthos Therapeutics, Inc.
• Original Study Sponsor: Same as current

Collaborators

• The TIMI Study Group
• Laboratory Corporation of America

• Investigators: Not Provided
• PRS Account: Anthos Therapeutics, Inc.
• Verification Date: March 2024