An Open Label Extension Trial of Eculizumab in Relapsing NMO Patients

Neuromyelitis Optica Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02003144
• Other study ID #: ECU-NMO-302
• Secondary ID: 2013-001151-12
• Status: Completed
• Phase: Phase 3
• Start date: January 12, 2015
• Est. completion date: July 12, 2021

Study information

• Verified date: July 2022
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: July 12, 2021
• Est. primary completion date: July 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Patients who have withdrawn from the ECU-NMO-301 trial as a result of an AE related to trial drug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

Related Conditions & MeSH terms

• Neuromyelitis Optica
• Neuromyelitis Optica Spectrum Disorder

Intervention

Biological:
• eculizumab

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Colombia,  Croatia,  Czechia,  Denmark,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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