Efficacy and Safety of MAA868 in Patients With Atrial Fibrillation

• ClinicalTrials.gov Identifier: NCT03398434
• Recruitment Status: Withdrawn
• First Posted: January 12, 2018
• Last Update Posted: October 8, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The purpose of this study is to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of MAA868 compared to apixaban in patients with atrial fibrillation.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation	Drug: MAA868; Drug: Apixaban	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a randomized, open-label, blinded endpoint evaluation, active controlled, dose-range finding study.
• Masking: Single (Outcomes Assessor)
• Masking Description: blinded (with majuscule) endpoint evaluation
• Primary Purpose: Basic Science
• Official Title: A Multicenter, Randomized, Open-label, Active-controlled, Dose-range Finding Study to Assess the Pharmacodynamic Parameters, Safety and Tolerability of MAA868 and Its Effect on Thrombogenesis Biomarkers Compared to Apixaban in Patients With Atrial Fibrillation
• Estimated Study Start Date: October 16, 2018
• Estimated Primary Completion Date: November 28, 2019
• Estimated Study Completion Date: January 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: MAA868 low dose regimen; patients receive dose monthly.	Drug: MAA868; 3 MAA868 doses, single administration, subcutaneous,
Experimental: MAA868 middle dose regimen; patients receive dose monthly.	Drug: MAA868; 3 MAA868 doses, single administration, subcutaneous,
Experimental: MAA868 high dose regimen; patients receive dose monthly.	Drug: MAA868; 3 MAA868 doses, single administration, subcutaneous,
Active Comparator: Apixaban; Apixaban 5 mg b.i.d	Drug: Apixaban; Apixaban 5 mg b.i.d

Outcome Measures

Primary Outcome Measures :

1. number of patients achieving FXI inhibition ≥ 80% at trough after monthly dosing at 3 dose levels of MAA868 inhibition [ Time Frame: month 3 ]
   Occurrence of achieving ≥ 80% inhibition of FXI (< 20% free FXI) following 3 months of treatment.

Secondary Outcome Measures :

1. number of patients achieving FXI inhibition ≥ 80% at trough after the first and second dose at 3 dose levels of MAA868 [ Time Frame: Month 1 and 2 ]
   Occurrence of achieving ≥ 80% inhibition of FXI (< 20% free FXI) at trough on Month 1 and Month 2
2. Number of patients with incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period. [ Time Frame: day 1 to day 91 ]
   Incidence of major or clinically relevant non-major bleeding events
3. the effect of MAA868 on D dimer and other thrombogenesis biomarkers as indicators of efficacy compared to compotator [ Time Frame: Days 31, 61 and 91 ]
   Change from baseline to Day 31, Day 61 and Day 91 in thrombogenesis biomarkers (D-dimer, prothrombin fragment 1.2 (F1.2), thrombin-antithrombin III-complexes (TAT), fibrinogen).

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male and female patients ≥ 55 and < 85 years old
• Body weight between 50 and 130 kg inclusive
• Atrial fibrillation or atrial flutter, as documented by electrocardiography
• CHA2DS2-VASc risk score ≥ 2 for male and female patients. Male patients with CHA2DS2VASc risk score of 1 can be included if anticoagulation therapy is warranted.
• Either anticoagulant-naïve or receiving a stable treatment of a recommended dose of a new oral anticoagulant (NOAC) over the 8 weeks prior to screening.

Exclusion Criteria:

• History of stroke, transient ischemic attack or systemic embolism
• History of major bleeding during treatment with an anticoagulant or antiplatelet therapy in the last 12 months
• History of traumatic or non-traumatic intracranial, intraspinal or intra-ocular 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 hemodynamically significant valvular heart disease
• Uncontrolled hypertension defined as SBP/DBP ≥ 160/100 mmHg at the screening visit
• Heart failure NYHA class IV in the 3 months prior to the screening visit
• Dual antiplatelet therapy. Treatment with a P2Y12 inhibitor or low dose aspirin (≤ 100 mg/d) is allowed but not both.
• Severe renal impairment (creatinine clearance < 30 mL/min) at the screening visit

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03398434
• Other Study ID Numbers: CMAA868A2202; 2017-002741-29 ( EudraCT Number )
• First Posted: January 12, 2018
• Last Update Posted: October 8, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

MAA868; apixaban; atrial fibrillation; anticoagulant; Factor XI; D-dimer; systemic thromboembolic events

Additional relevant MeSH terms:

Atrial Fibrillation; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Apixaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants