C1-esterase Inhibitor (Cinryze) for Acute Treatment of Neuromyelitis Optica Exacerbation

Neuromyelitis Optica Clinical Trial

Official title: Phase 1b Study of C1-esterase Inhibitor (Cinryze) With Standard of Care for Acute Treatment of Neuromyelitis Optica Exacerbations

Status Completed

Clinical Trial Summary

The overall objective is to evaluate the tolerability/safety and preliminary efficacy of CINRYZE® (C1 esterase inhibitor [human]) as add-on therapy for treatment of acute optic neuritis and/or transverse myelitis in NMO and NMOSD.

Primary Objective: To evaluate the safety and tolerability of 3-5 doses of 1000 - 2000 Units intravenous CINRYZE in NMO/NMOSD patients during an acute exacerbation.

Secondary Objectives:

• To determine the frequency of adverse events with CINRYZE in this patient population.

• To determine the effect of CINRYZE on NMO clinical scores (Expanded Disability Status Scale and Low Contrast Visual Acuity).

• To compare the change in MRI lesion size and extent following a course of CINRYZE.

Clinical Trial Description

The rationale for using C1-esterase inhibitor (CINRYZE) in NMO is based on pathology showing a role for complement in active NMO lesions. NMO is not unique in involving complement, which may have a pathogenic role in other demyelinating diseases including multiple sclerosis. However, NMO is characterized by its complement involvement depositing in a rim or rosette pattern in all/most active lesions. In vitro, complement mediates damage initiated by anti-AQP4 antibody binding to astrocytes. The effector of antibody triggered cell damage is the complement cascade and blocking the complement cascade with C1-inhibitor prevents damage ex vivo. Based on mounting evidence, the consensus in the field is that prevention of the complement cascade in the CNS would ameliorate the damage caused in NMO inflammatory attacks. In contrast to a prevention trial, this study would provide for complement inhibition only during an active NMO attack. This approach is designed to administer the inhibitory drug when complement damage is at its peak which minimizes adverse effects from prolonged complement inhibition.

Patients with NMO do not lack natural C1-esterase inhibitor, but artificially tipping the balance to suppress the complement pathways using purified human C1-esterase inhibitor in patients with hyperactive complement activation has been shown to be beneficial in myocardial infarction and sepsis. Similarly, the rationale for adding human C1-esterase inhibitor to the treatment for NMO acute exacerbations is to tip the balance toward complement suppression in an effort to reduce complement-mediated neurologic damage.

This is a phase 1b open-label, interventional proof-of-concept study in which all subjects will receive 3 daily infusions of 2000 Units of intravenous CINRYZE at the onset of an NMO exacerbation, plus an additional 2 infusions of 1000 Units of intravenous CINRYZE during a second treatment phase with plasma exchange, if necessary. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuromyelitis Optica

• NCT number: NCT01759602
• Study type: Interventional
• Source: Johns Hopkins University
• Status: Completed
• Phase: Phase 1
• Start date: January 2013
• Completion date: November 2013