Effectiveness and safety of MAA868 in patients with irregular heartbeat

Phase 1

Conditions: atrial fibrillation
MedDRA version: 20.0Level: PTClassification code 10003658Term: Atrial fibrillationSystem Organ Class: 10007541 - Cardiac disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2017-002741-29-DE

Lead Sponsor: ovartis Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 600

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.
- See full inclusion criteria in study protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 420

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.
- See full exclusion criteria in study protocol.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Occurrence of achieving =80% inhibition of FXI (< 20% free FXI) following 3 months of treatment.;Secondary Objective: - Occurrence of achieving =80% inhibition of FXI (< 20% free FXI) at trough on Month 1 and Month 2.<br>- Incidence of major or clinically relevant non-major bleeding events.<br>- Change from baseline to Day 31, Day 61 and Day 91 in thrombogenesis biomarkers (D-dimer, prothrombin fragment 1.2 (F1.2), thrombinantithrombin III-complexes (TAT), fibrinogen).;Primary end point(s): Number of patients achieving FXI inhibition =80% at trough after monthly dosing at 3 dose levels of MAA868 inhibition.;Timepoint(s) of evaluation of this end point: month 3

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Number of patients achieving FXI inhibition = 80% at trough after the first and second dose at 3 dose levels of MAA868.<br>- Number of patients with incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period.<br>- The effect of MAA868 on D-dimer and other thrombogenesis biomarkers as indicators of efficacy compared to comparator.;Timepoint(s) of evaluation of this end point: - Month 1 and 2.<br>- Day 1 to day 91.<br>- Days 31, 61 and 91.