Effectiveness and safety of MAA868 in patients with irregular heartbeat

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2017-002741-29-SE
• Date of registration: 16/01/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma AG
• Public title: Effectiveness and safety of MAA868 in patients with irregular heartbeat
• Scientific 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
• Date of first enrolment: 04/04/2018
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002741-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Randomized, open-label study with blinded endpoint evaluation; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Finland, Germany, Hungary, Iceland, Japan, Netherlands, Russian Federation, Sweden, Switzerland, United States

Contacts

• Name: Medical information
• Affiliation: Novartis Sverige AB

• Name: Medical information
• Affiliation: Novartis Sverige AB

Key inclusion & exclusion 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.
- 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

atrial fibrillation
MedDRA version: 20.0 Level: PT Classification code 10003658 Term: Atrial fibrillation System Organ Class: 10007541 - Cardiac disorders

Intervention(s)

Product Code: MAA868
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: not available
Current Sponsor code: MAA868
Other descriptive name: MAA868
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-

Trade Name: Eliquis
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: APIXABAN
Other descriptive name: Eliquis
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Eliquis
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: APIXABAN
Other descriptive name: Eliquis
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Main Objective: Occurrence of achieving =80% inhibition of FXI (< 20% free FXI) following 3 months of treatment.

Primary end point(s): Number of patients achieving FXI inhibition =80% at trough after monthly dosing at 3 dose levels of MAA868 inhibition.

Secondary Objective: - Occurrence of achieving =80% inhibition of FXI (< 20% free FXI) at trough on Month 1 and Month 2.
- Incidence of major or clinically relevant non-major bleeding events.
- 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).

Timepoint(s) of evaluation of this end point: month 3

Secondary Outcome(s)

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.
- Number of patients with incidence of major or clinically relevant non-major (CRNM) bleeding events during the treatment period.
- 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.
- Day 1 to day 91.
- Days 31, 61 and 91.

Secondary ID(s)

CMAA868A2202

2017-002741-29-DE

Source(s) of Monetary Support

Novartis Pharma AG