An Open Label Extension Trial of Eculizumab in Relapsing NMO Patients

A Phase III, Open-label, Extension Trial of ECU-NMO-301 to Evaluate the Safety and Efficacy of Eculizumab in Patients With Relapsing Neuromyelitis Optica (NMO)

The purpose of this study is to determine whether eculizumab long-term use is safe and effective in patients with relapsing NMO.

Study Overview

• Status: Completed
• Conditions: Neuromyelitis Optica; Neuromyelitis Optica Spectrum Disorder
• Intervention / Treatment: Biological: eculizumab

Detailed Description

This study is an open label extension study to confirm the long term safety and efficacy of eculizumab in subjects with relapsing NMO who have completed the initial double-blind, randomized, placebo-controlled trial ECU-NMO-301.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma, Buenos Aires, Argentina, C1425AGP
    • Hospital General de Agudos Juan Antonio Fernandez
  • Ciudad Autonoma, Buenos Aires,, Argentina, C1221ADC
    • Hospital General de Agudos Dr. J. M. Ramos Mejia
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, B1629ODT
      • Hospital Universitario Austral
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000BZL
      • Fundacion Rosarina de Neuro Rehabilitacion
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia
      • Brain and Mind Research Institute
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
• Colombia
  • Santander
    • Floridablanca, Santander, Colombia
      • Fundacion Cardiovascular de Colombia
• Croatia
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb
• Czechia
  • Praha, Czechia
    • VFN v Praze
  • Teplice, Czechia, 415 01
    • Krajska zdravotni, a.s. - Nemocnice
• Denmark
  • Arhus, Denmark, 8000
    • Århus Universitetshospital
• Germany
  • Rostock, Germany, 18147
    • Universitaetsmedizin Rostock
  • Baden Wuerttemberg
    • Heidelberg, Baden Wuerttemberg, Germany, 69120
      • University Hospital Heidelberg
  • Bayern
    • Munich, Bayern, Germany, 81675
      • Neurologische Klinik und Poliklinik
  • Nordrhein Westfalen
    • Dusseldorf, Nordrhein Westfalen, Germany, 40225
      • University Hospital Heinrich Heine University
• Hong Kong
  • Shatin, Hong Kong
    • Prince of Wales Hospital
• Italy
  • Catania, Italy, 95123
    • Policlinico di Catania
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova
  • Rome, Italy, 00178
    • Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Tokio, Japan
    • National Center Hospital, NCNP
  • Chiba-Ken
    • Chiba-shi, Chiba-Ken, Japan, 260-8677
      • Chiba University Hospital
  • HyogoKen
    • Nishinomiya-shi, HyogoKen, Japan
      • Hyogo College of Medicine Hospital
  • Kyoto-Fu
    • Kyoto-shi, Kyoto-Fu, Japan, 604-8453
      • Kyoto Min-iren Chuo Hospital
  • Miyagi-Ken
    • Sendai-shi, Miyagi-Ken, Japan, 980-8574
      • Tohoku University Hospital
  • Yamaguchi-Ken
    • Ube-shi, Yamaguchi-Ken, Japan, 755-8505
      • Yamaguchi University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 136-705
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 110744
    • Seoul University National Hospital
  • Seoul, Korea, Republic of, 136-705
    • Severance Hospital, Yonsei University
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Hospital Umum Sarawak
• Russian Federation
  • Kazan, Russian Federation, 420021
    • Republican Clinical Hospital for Rehabilitation of Healthcare Ministry of Republic of Tatarstan
  • Krasnoyarsk, Russian Federation, 660037
    • SBEI "Krasnoyarsk SMU n.a. Prof. V.F. Voyno-Yasenetsky"
  • Novosibirsk, Russian Federation, 630068
    • Federal State Budget Institution of Healthcare - Siberian District Medical Center of FMBA of Russia
  • Rostov-on Don, Russian Federation
    • SEIHPE "Rostov SMU of MoH of RF"
• Spain
  • Cordoba, Spain, 14404
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28040
    • Hospital Universitario Clinico San Carlos
  • Bizkaia
    • Barakaldo, Bizkaia, Spain, 48903
      • Hospital de Cruces
• Taiwan
  • Taipei, Taiwan
    • Cheng Hsin General Hospital
• Thailand
  • Pathum Thani, Thailand
    • Thammasat University Hospital
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty
  • Edirne, Turkey
    • Trakya University Medical Faculty
  • Izmir, Turkey, 35340
    • Dokuz Eylul University Medicine Faculty
  • Kocaeli, Turkey
    • Kocaeli University Medical Faculty
  • Samsun, Turkey
    • Ondokuz Mayis Univ. Med. Fac.
• United Kingdom
  • Liverpool, United Kingdom, L97LJ
    • The Walton Centre
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • California
    • Oceanside, California, United States, 92056
      • The Research Center of Southern California
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami McKnight Brain Institute
    • Orlando, Florida, United States, 32806
      • Neurological Services of Orlando
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Allied Physicians Inc. of Fort Wayne
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Nicholasville, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10016
      • Multiple Sclerosis Comprehensive Care Center NYU Langone Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43214
      • Ohio Health Reserach Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania School of Medicine
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75246
      • Multiple Sclerosis Treatment Center of Dallas
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Patient completed the ECU-NMO-301 trial
2. Patient has given written informed consent

Key Exclusion Criteria:

1. Patients who have withdrawn from the ECU-NMO-301 trial as a result of an AE related to trial drug
2. Female patients who are pregnant, breastfeeding, or intend to conceive during the course of the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eculizumab; Eculizumab intravenous infusion every two weeks.	Biological: eculizumab; Other Names: Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events	An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-emergent adverse events (TEAEs) were defined as an AE with onset on or after the first study drug dose in Study ECU-NMO-302. A serious adverse event (SAE) was defined as an untoward medical occurrence that at any dose either results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.	Baseline up to end of study (up to 6.5 years)
Number of Participants With At Least 1 Post Baseline Columbia-Suicide Severity Rating Scale (C-SSRS) Assessment (Suicide-Related Thoughts or Behaviours) Abnormality	The C-SSRS is a validated questionnaire to capture occurrence, severity, and frequency of suicide-related thoughts and behaviours, and has a binary response (yes/no). Suicidal Ideation: a "yes" answer to any one of 5 suicidal ideation questions: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Planned) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; and Active Suicidal Ideation with Specific Plan and Intent. Suicidal Behaviour: a "yes" answer to any of 5 suicidal behaviour questions: Preparatory Acts or Behaviour, Aborted Attempt, Interrupted Attempt, Actual Attempt (non-fatal), and Completed Suicide. Suicidal Ideation or Behaviour: a "yes" answer to the following question: Self-injurious behaviour without suicidal intent.	Baseline up to end of study (up to 6.5 years)
Number of Participants With An On-trial Relapse as Determined by The Treating Physician	An On-trial Relapse was defined as a new onset of neurologic symptoms or worsening of existing neurologic symptoms with an objective change (clinical sign) on neurologic examination that persisted for more than 24 hours as confirmed by the treating physician.	Baseline up to end of study (up to 6.5 years)
On-Trial Annualized Relapse Rate (ARR) as Determined by The Treating Physician	The On-trial ARR was computed as the total number of relapses divided by the total number of participant years in the study period.	Baseline up to end of study (up to 6.5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Expanded Disability Status Scale (EDSS) Score	Disease-related disability was measured by the EDSS. The EDSS quantifies disability in 8 Functional Systems (FS) and allows neurologists to assign a Functional System Score (FSS) in each of these. The Functional Systems are pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other. The EDSS is an ordinal clinical rating scale that ranges from 0 (normal neurologic examination) to 10 (death) in half-point increments. A decrease in score indicates improvement. Baseline was defined as the last available assessment prior to the first study drug infusion in Study ECU-NMO-302.	Baseline, Weeks 52, 104 and 156
Change From Baseline in Modified Rankin Scale (mRS) Score	Disease-related disability was measured by the mRS score. The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered from a neurological disability. The scale ranges from 0 (no symptoms at all) to 6 (death) in whole-point increments. A decrease in score indicates improvement. Baseline was defined as the last available assessment prior to the first study drug infusion in Study ECU-NMO-302.	Baseline, Weeks 52, 104 and 156
Change From Baseline in Hauser Ambulation Index (HAI) in Participants With Abnormal Baseline Ambulatory Function	The HAI evaluates gait and was used to assess the time and effort used by the participant to walk 25 feet (8 meters). The scale ranges from 0 to 9, with 0 being the best score (asymptomatic; fully active) and 9 being the worst (restricted to wheelchair; unable to transfer self independently). A decrease in score indicates improvement. Baseline is defined as the last available assessment prior to the first study drug infusion in Study ECU-NMO-302.	Baseline, Weeks 52, 104 and 156
Change From Baseline in European Quality of Life (EuroQoL) 5-Dimension Visual Analog Scale (EQ-5D VAS) Health Status Score	The EQ-5D is a generic, standardized participant self-administered health status instrument. EQ-5D general health status can also be measured by a visual analog scale (EQ-5D VAS). EQ-5D-VAS recorded the participant's self-rated health on a vertical visual analog scale (VAS) that allowed the participants to indicate their health state that ranged from 0 (worst imaginable) to 100 (best imaginable). Baseline is defined as the last available assessment prior to the first study drug infusion in Study ECU-NMO-302.	Baseline, Weeks 52, 104 and 156
Change From Baseline in Kurtzke Visual Functional System Scores (FSS) in Participants With Abnormal Baseline Visual Function	The EDSS assesses multiple Kurtzke functional systems in the context of a standard neurological exam, including visual function. The visual score ranges from 0 to 6. A score of 0 implies the participant has normal visual function. Higher scores represent worse disability. Baseline is defined as the last available assessment prior to the first study drug infusion in Study EC-NMO-302.	Baseline, Weeks 52, 104 and 156

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals

Publications and helpful links

General Publications

• Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, O'Toole O, Wingerchuk DM. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013 Jun;12(6):554-62. doi: 10.1016/S1474-4422(13)70076-0. Epub 2013 Apr 26.
• Pittock SJ, Fujihara K, Palace J, Berthele A, Kim HJ, Oreja-Guevara C, Nakashima I, Levy M, Shang S, Yountz M, Miller L, Armstrong R, Wingerchuk DM; PREVENT Study Group. Eculizumab monotherapy for NMOSD: Data from PREVENT and its open-label extension. Mult Scler. 2022 Mar;28(3):480-486. doi: 10.1177/13524585211038291. Epub 2021 Sep 9.
• Kim HJ, Nakashima I, Viswanathan S, Wang KC, Shang S, Miller L, Yountz M, Wingerchuk DM, Pittock SJ, Levy M, Berthele A, Totolyan N, Palace J, Barnett MH, Fujihara K; PREVENT Study Group. Eculizumab in Asian patients with anti-aquaporin-IgG-positive neuromyelitis optica spectrum disorder: A subgroup analysis from the randomized phase 3 PREVENT trial and its open-label extension. Mult Scler Relat Disord. 2021 May;50:102849. doi: 10.1016/j.msard.2021.102849. Epub 2021 Feb 20.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2015
• Primary Completion (Actual): July 12, 2021
• Study Completion (Actual): July 12, 2021

Study Registration Dates

• First Submitted: November 18, 2013
• First Submitted That Met QC Criteria: December 2, 2013
• First Posted (Estimate): December 6, 2013

Study Record Updates

• Last Update Posted (Actual): August 23, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Relapse; Eculizumab; Optic Neuritis; Transverse Myelitis; Devic's disease; NMO-IgG; Neuromyelitis Optica Spectrum Disorder; CNS Autoimmune Disorders; Demyelinating Disorders; Long-term safety study; Extension trial
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Optic Neuritis; Neuromyelitis Optica; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: ECU-NMO-302; 2013-001151-12 (EudraCT Number)