The primary objective of this study is to evaluate the proportion of patients achieving FXI inhibition * 80% at trough (Day 91) after monthly dosing at 3 dose levels of MAA868.
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
FXI-inhibition * 80% at trough (Day 91) after having received MAA868 3 times
Secondary outcome
Objective 1:
To evaluate the proportion of patients achieving FXI inhibition * 80% at trough
after the first and second dose (Day 31 and Day 61) at 3 dose levels of MAA868.
Objective 2:
To evaluate the incidence of major bleeding events, clinically relevant
non-major bleeding events and total bleeding with MAA868 relative to apixaban
during the treatment period.
Objective 3:
To assess the effect of MAA868 on D-dimer and other thrombogenesis biomarkers
as indicators of efficacy at Day 31, Day 61 and Day 91 compared to apixaban.
Objective 4:
To evaluate the safety and tolerability of MAA868 compared to apixaban.
Background summary
Atrium Fibrillation is the most common cardiac arrhythmia, which effects more
than 6 million people in Europe and is associated with a 4-5 fold increase in
embolic stroke.
Vit K antagonists (e.g. Warfarine) and NOAC's are effective in reducing stroke
and systemic embolism, however, bleeding risk continues to be high.
Factor XI holds important roles in both the intrinsic and extrinsic coagulation
pathways and in brdiging the initiation and amplification phases of plasmatic
hemostasis, yet plays a minor role in hemostasis after vessel injury and is
therefore associated with a lower incidence of ischemic stroke, cardiovascular
and venous thrombotic events.
This hypothesis is supported by the existence of people with a Factor XI
deficiency. These people have reduced risk of developing thrombosis and related
complications.
Study objective
The primary objective of this study is to evaluate the proportion of patients
achieving FXI inhibition * 80% at trough (Day 91) after monthly dosing at 3
dose levels of MAA868.
Study design
This is a randomized, open-label, blinded endpoint evaluation, active
controlled, dose-range finding study. After a screening period of 1 to 2 weeks,
patients will be randomized to 1 of 4 treatment groups (low, medium or high
dose MAA868 or apixaban) in a 1:1:1:1 ratio and followed during a 90-day
treatment period. Randomization will be stratified by country and whether
patients are anticoagulant naïve (Yes/No) at screening. Patients will be
transitioned to a NOAC and/or other standard of care therapy at the
investigator's discretion on Day 91 and followed up to Day 170.
Intervention
- MAA868 180 mg s.c 3x (once monthly)
- MAA868 150 mg s.c. 3x (once monthly)
- MAA868 150 mg s.c. 1x + 120 mg s.c. 2x (once mothly)
- Apixaban 5 mg b.i.d. during 90 days
Study burden and risks
Adverse effects of study medication and study procedures.
Change of anti-coagulation medication.
Physical examination: 9x
Length: 1x
Weight: 3x
Vital functions (RR/Pulse/Bodyteperature): 9x
Triple ECG: 6x
Collection of bloodsamples: 9x
Urine test (dipstick): 9x
Pregnancy test (urine), when applicable: 6x
S.c.administration of MAA868: 3x, when applicable.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002741-29-NL |
| ClinicalTrials.gov | NCT03398434 |
| CCMO | NL63967.018.17 |