An Open Label Extension Trial of Eculizumab in Relapsing NMO Patients

NCT02003144 | Completed Phase 3 Results DMC

• 2 other identifiers: ECU-NMO-3022013-001151-12
• Study Type: interventional
• Target: 119
• Locations: 20 countries
• Sites: 69

Brief Summary

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

Conditions

Neuromyelitis Optica; Neuromyelitis Optica Spectrum Disorder

Keywords

Long-term safety study; Extension trial; Eculizumab; Neuromyelitis Optica Spectrum Disorder; Devic's disease; Transverse Myelitis; Optic Neuritis; Relapse; NMO-IgG; CNS Autoimmune Disorders; Demyelinating Disorders

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• Change From Baseline in Expanded Disability Status Scale (EDSS) Score

  Baseline, Weeks 52, 104 and 156

• Change From Baseline in Modified Rankin Scale (mRS) Score

  Baseline, Weeks 52, 104 and 156

• Change From Baseline in Hauser Ambulation Index (HAI) in Participants With Abnormal Baseline Ambulatory Function

  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

  Baseline, Weeks 52, 104 and 156

• Change From Baseline in Kurtzke Visual Functional System Scores (FSS) in Participants With Abnormal Baseline Visual Function

  Baseline, Weeks 52, 104 and 156

Study Arms (1)

Eculizumab

EXPERIMENTAL

Eculizumab intravenous infusion every two weeks.

Biological: eculizumab

Interventions

eculizumab BIOLOGICAL

Also known as: Soliris

Eculizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient completed the ECU-NMO-301 trial
• Patient has given written informed consent

You may not qualify if:

• Patients who have withdrawn from the ECU-NMO-301 trial as a result of an AE related to trial drug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

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (69)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

The Research Center of Southern California

Oceanside, California, 92056, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Miami McKnight Brain Institute

Miami, Florida, 33136, United States

Location

Neurological Services of Orlando

Orlando, Florida, 32806, United States

Location

Allied Physicians Inc. of Fort Wayne

Fort Wayne, Indiana, 46805, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Baptist Health Lexington

Nicholasville, Kentucky, 40503, United States

Location

Johns Hopkins University Medical Center

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Multiple Sclerosis Comprehensive Care Center NYU Langone Medical Center

New York, New York, 10016, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Ohio Health Reserach Institute

Columbus, Ohio, 43214, United States

Location

University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Multiple Sclerosis Treatment Center of Dallas

Dallas, Texas, 75246, United States

Location

The University of Texas Health Science

San Antonio, Texas, 78229, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Hospital Universitario Austral

Pilar, Buenos Aires, B1629ODT, Argentina

Location

Fundacion Rosarina de Neuro Rehabilitacion

Rosario, Santa Fe Province, S2000BZL, Argentina

Location

Hospital General de Agudos Juan Antonio Fernandez

Ciudad Autonoma, Buenos Aires, C1425AGP, Argentina

Location

Hospital General de Agudos Dr. J. M. Ramos Mejia

Ciudad Autonoma, Buenos Aires,, C1221ADC, Argentina

Location

Brain and Mind Research Institute

Camperdown, New South Wales, Australia

Location

St. Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Fundacion Cardiovascular de Colombia

Floridablanca, Santander Department, Colombia

Location

Clinical Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

VFN v Praze

Prague, Czechia

Location

Krajska zdravotni, a.s. - Nemocnice

Teplice, 415 01, Czechia

Location

Århus Universitetshospital

Aarhus, 8000, Denmark

Location

University Hospital Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Neurologische Klinik und Poliklinik

Munich, Bavaria, 81675, Germany

Location

University Hospital Heinrich Heine University

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitaetsmedizin Rostock

Rostock, 18147, Germany

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Policlinico di Catania

Catania, 95123, Italy

Location

Azienda Ospedaliera Universitaria

Napoli, 80131, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza

Rome, 00178, Italy

Location

Chiba University Hospital

Chiba, Chiba, 260-8677, Japan

Location

Hyogo College of Medicine Hospital

Nishinomiya-shi, HyogoKen, Japan

Location

Kyoto Min-iren Chuo Hospital

Kyoto, Kyoto, 604-8453, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Yamaguchi University Hospital

Ube-shi, Yamaguchi, 755-8505, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

National Center Hospital, NCNP

Tokyo, Japan

Location

Hospital Umum Sarawak

Kuching, Sarawak, 93586, Malaysia

Location

Hospital Kuala Lumpur

Kuala Lumpur, 50586, Malaysia

Location

Republican Clinical Hospital for Rehabilitation of Healthcare Ministry of Republic of Tatarstan

Kazan', 420021, Russia

Location

SBEI "Krasnoyarsk SMU n.a. Prof. V.F. Voyno-Yasenetsky"

Krasnoyarsk, 660037, Russia

Location

Federal State Budget Institution of Healthcare - Siberian District Medical Center of FMBA of Russia

Novosibirsk, 630068, Russia

Location

SEIHPE "Rostov SMU of MoH of RF"

Rostov-on-Don, Russia

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 410-769, South Korea

Location

Seoul University National Hospital

Seoul, 110744, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Korea University Anam Hospital

Seoul, 136-705, South Korea

Location

Severance Hospital, Yonsei University

Seoul, 136-705, South Korea

Location

Hospital de Cruces

Barakaldo, Bizkaia, 48903, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14404, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, 28040, Spain

Location

Cheng Hsin General Hospital

Taipei, Taiwan

Location

Thammasat University Hospital

Pathum Thani, Thailand

Location

Hacettepe University Medical Faculty

Ankara, 06100, Turkey (Türkiye)

Location

Trakya University Medical Faculty

Edirne, Turkey (Türkiye)

Location

Dokuz Eylul University Medicine Faculty

Izmir, 35340, Turkey (Türkiye)

Location

Kocaeli University Medical Faculty

Kocaeli, Turkey (Türkiye)

Location

Ondokuz Mayis Univ. Med. Fac.

Samsun, Turkey (Türkiye)

Location

The Walton Centre

Liverpool, L97LJ, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 23623397 BACKGROUND

• 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.

  PMID: 34498507 DERIVED

• 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.

  PMID: 33676197 DERIVED

MeSH Terms

Conditions

Neuromyelitis Optica; Myelitis, Transverse; Optic Neuritis; Recurrence; Demyelinating Diseases

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases; Myelitis; Central Nervous System Infections; Infections; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Central Nervous System Diseases; Spinal Cord Diseases; Neurodegenerative Diseases; Neuroinflammatory Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

+1 855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2013
• First Posted: December 6, 2013
• Study Start: January 12, 2015
• Primary Completion: July 12, 2021
• Study Completion: July 12, 2021
• Last Updated: August 23, 2022
• Results First Posted: August 23, 2022

Record last verified: 2022-07

Locations

HK (1); AU (2); ES (3); CO (1); RU (4); KR (5); CR (1); US (19); TW (1); DK (1); TH (1); JP (7); GB (1); TU (5); AR (4); CZ (2); CA (1); IT (4); DE (4); MY (2)