Prevention of Thromboembolic Events in Total Knee Replacement Patients

A Multicenter, Randomized, Open-label, Blinded Endpoint Evaluation, Active-controlled Phase 2 Study to Compare the Efficacy and Safety of s.c. MAA868 Versus s.c. Enoxaparin in Adult Patients Undergoing Unilateral Total Knee Arthroplasty

The purpose of the study is to find out whether MAA868, is able to prevent blood clots following your medical condition (surgery for knee replacement)

Study Overview

• Status: Withdrawn
• Conditions: Thrombotic Disorders
• Intervention / Treatment: Drug: MAA868; Drug: Enoxaparin

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Scheduled to undergo elective unilateral total knee arthroplayts (TKA)
• Willing to comply with study requirements including bilateral venography at Day 12 ± 2 days
• Body weight between 50 kg and 130 kg inclusive.
• Normal aPTT, PT, INR at screening

Exclusion Criteria:

History of arterial or venous thromboembolism; abnormally extended primary or secondary bleeding after trauma or intervention, stroke, transient ischemic attack or traumatic or non-traumatic intracranial bleed; bleeding disorder; MI or unstable angina pectoris within 12 months of the screening; Uncontrolled hypertension (SBP/DBP ≥ 150/95 mmHg at the screening).

Medications that increase the risk of bleeding, including antiplatelet (such as aspirin), anticoagulant and fibrinolytic agents; eGFR < 60 mL/min/1.73m2; Poorly controlled diabetes (HbA1C >10%); Liver dysfunction (ALT/AST >3 xULN or TBL >2 x ULN); BMI ≥ 40 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MAA868 dose 1; MAA868 dose 1, single administration, subcutaneous	Drug: MAA868; MAA868 dose 1 and dose 2, single administration, subcutaneous,
EXPERIMENTAL: MAA868 dose 2; MAA868 dose 2, single administration, subcutaneous	Drug: MAA868; MAA868 dose 1 and dose 2, single administration, subcutaneous,
ACTIVE_COMPARATOR: Enoxaparin; Enoxaparin 40mg, once daily (o.d.) for 10 days	Drug: Enoxaparin; Enoxaparin 40 mg, o.d X 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with confirmed composite endpoint	Occurrence of confirmed composite endpoint of asymptomatic deep vein thrombosis (DVT), confirmed symptomatic venous thromboembolic events (VTE), fatal pulmonary embolism (PE) or unexplained death	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with composite bleeding	Occurrence of confirmed composite endpoint of major bleeding and clinically relevant non-major (CRNM) bleeding events	Day 1 to Day 50
Number of patients with composite venous thromboembolic events (VTE)	Occurrence of confirmed composite endpoint of asymptomatic deep vein thrombosis (DVT), Confirmed symptomatic venous thromboembolic events (VTE), fatal pulmonary embolism (PE) or unexplained death	Day 1 to Day 110

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 3, 2018
• Primary Completion (ANTICIPATED): January 8, 2020
• Study Completion (ANTICIPATED): April 17, 2020

Study Registration Dates

• First Submitted: January 3, 2018
• First Submitted That Met QC Criteria: January 3, 2018
• First Posted (ACTUAL): January 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: biologic,; venous thromboembolism,; unilateral knee arthroplasty
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: CMAA868A2201; 2017-002925-39 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No