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NCT02003144

An Open Label Extension Trial of Eculizumab in Relapsing NMO Patients

Completed Phase 3 Results posted Last updated 23 August 2022
What this trial tests

Phase 3 trial testing eculizumab in Neuromyelitis Optica in 119 participants. Completed in 12 July 2021.

Timeline
12 January 2015
Primary endpoint
12 July 2021
12 July 2021

Quick facts

Lead sponsorAlexion Pharmaceuticals, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment119
Start date12 January 2015
Primary completion12 July 2021
Estimated completion12 July 2021
Sites69 locations across Hong Kong, Colombia, Italy, Japan, Malaysia, Taiwan, South Korea, Croatia

Drugs / interventions tested

Conditions studied

Sponsor

Alexion Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Neuromyelitis Optica or Neuromyelitis Optica Spectrum Disorder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events Primary · Baseline up to end of study (up to 6.5 years)

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 exi

TEAEs
GroupValue95% CI
Placebo/Eculizumab41
Eculizumab/Eculizumab70
SAEs
GroupValue95% CI
Placebo/Eculizumab14
Eculizumab/Eculizumab26
Number of Participants With At Least 1 Post Baseline Columbia-Suicide Severity Rating Scale (C-SSRS) Assessment (Suicide-Related Thoughts or Behaviours) Abnormality Primary · Baseline up to end of study (up to 6.5 years)

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: Preparato

Suicidal Ideation
GroupValue95% CI
Placebo/Eculizumab4
Eculizumab/Eculizumab5
Suicidal Behavior
GroupValue95% CI
Placebo/Eculizumab0
Eculizumab/Eculizumab1
Suicidal Ideation or Behavior
GroupValue95% CI
Placebo/Eculizumab4
Eculizumab/Eculizumab5
Number of Participants With An On-trial Relapse as Determined by The Treating Physician Primary · Baseline up to end of study (up to 6.5 years)

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.

GroupValue95% CI
Placebo/Eculizumab5
Eculizumab/Eculizumab8
On-Trial Annualized Relapse Rate (ARR) as Determined by The Treating Physician Primary · Baseline up to end of study (up to 6.5 years)

The On-trial ARR was computed as the total number of relapses divided by the total number of participant years in the study period.

GroupValue95% CI
Placebo/Eculizumab0.128± 0.4576
Eculizumab/Eculizumab0.061± 0.2186
Change From Baseline in Expanded Disability Status Scale (EDSS) Score Secondary · Baseline, Weeks 52, 104 and 156

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-

Baseline
GroupValue95% CI
Placebo/Eculizumab4.34± 1.879
Eculizumab/Eculizumab3.97± 1.736
Change from Baseline at Week 52
GroupValue95% CI
Placebo/Eculizumab-0.24± 0.721
Eculizumab/Eculizumab0.01± 0.571
Change from Baseline at Week 104
GroupValue95% CI
Placebo/Eculizumab-0.39± 0.830
Eculizumab/Eculizumab-0.11± 0.536
Change from Baseline at Week 156
GroupValue95% CI
Placebo/Eculizumab-0.38± 1.003
Eculizumab/Eculizumab-0.38± 1.057
Change From Baseline in Modified Rankin Scale (mRS) Score Secondary · Baseline, Weeks 52, 104 and 156

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
GroupValue95% CI
Placebo/Eculizumab2.39± 1.358
Eculizumab/Eculizumab1.88± 1.269
Change from Baseline at Week 52
GroupValue95% CI
Placebo/Eculizumab-0.27± 0.932
Eculizumab/Eculizumab-0.04± 0.458
Change from Baseline at Week 104
GroupValue95% CI
Placebo/Eculizumab-0.41± 1.182
Eculizumab/Eculizumab-0.14± 0.543
Change from Baseline at Week 156
GroupValue95% CI
Placebo/Eculizumab-0.62± 1.446
Eculizumab/Eculizumab-0.31± 0.602
Change From Baseline in Hauser Ambulation Index (HAI) in Participants With Abnormal Baseline Ambulatory Function Secondary · Baseline, Weeks 52, 104 and 156

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
GroupValue95% CI
Placebo/Eculizumab2.83± 2.123
Eculizumab/Eculizumab2.35± 2.257
Change from Baseline at Week 52
GroupValue95% CI
Placebo/Eculizumab-0.44± 1.132
Eculizumab/Eculizumab0.08± 0.816
Change from Baseline at Week 104
GroupValue95% CI
Placebo/Eculizumab-0.57± 1.777
Eculizumab/Eculizumab0.07± 1.033
Change from Baseline at Week 156
GroupValue95% CI
Placebo/Eculizumab-1.08± 1.706
Eculizumab/Eculizumab0.07± 1.269
Change From Baseline in European Quality of Life (EuroQoL) 5-Dimension Visual Analog Scale (EQ-5D VAS) Health Status Score Secondary · Baseline, Weeks 52, 104 and 156

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
GroupValue95% CI
Placebo/Eculizumab62.00± 22.012
Eculizumab/Eculizumab72.27± 20.941
Change from Baseline at Week 52
GroupValue95% CI
Placebo/Eculizumab2.22± 13.294
Eculizumab/Eculizumab-0.78± 12.388
Change from Baseline at Week 104
GroupValue95% CI
Placebo/Eculizumab0.05± 18.867
Eculizumab/Eculizumab1.28± 11.295
Change from Baseline at Week 156
GroupValue95% CI
Placebo/Eculizumab11.00± 19.374
Eculizumab/Eculizumab-4.13± 18.421
Change From Baseline in Kurtzke Visual Functional System Scores (FSS) in Participants With Abnormal Baseline Visual Function Secondary · Baseline, Weeks 52, 104 and 156

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
GroupValue95% CI
Placebo/Eculizumab3.75± 2.030
Eculizumab/Eculizumab3.60± 2.031
Change from Baseline at Week 52
GroupValue95% CI
Placebo/Eculizumab-0.08± 0.392
Eculizumab/Eculizumab-0.06± 0.569
Change from Baseline at Week 104
GroupValue95% CI
Placebo/Eculizumab-0.13± 0.352
Eculizumab/Eculizumab-0.10± 0.651
Change from Baseline at Week 156
GroupValue95% CI
Placebo/Eculizumab0.00± 0.000
Eculizumab/Eculizumab-0.29± 0.994

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to end of study (up to 6.5 years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo/Eculizumab
Serious: 14/41 (34%)
Deaths: 0/41
Eculizumab/Eculizumab
Serious: 26/78 (33%)
Deaths: 0/78
Eculizumab (Combined Total)
Serious: 40/119 (34%)
Deaths: 0/119

Serious adverse events (64 terms)

ReactionSystemPlacebo/EculizumabEculizumab/EculizumabEculizumab (Combined Total)
Urinary tract infectionInfections and infestations
Neuromyelitis optica spectrum disorderNervous system disorders
Cholecystitis acuteHepatobiliary disorders
Optic neuritisNervous system disorders
PneumoniaInfections and infestations
Pyelonephritis acuteInfections and infestations
UrosepsisInfections and infestations
Femoral neck fractureInjury, poisoning and procedural complications
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
OsteonecrosisMusculoskeletal and connective tissue disorders
LymphadenopathyBlood and lymphatic system disorders
Ventricular fibrillationCardiac disorders
GlaucomaEye disorders
Irritable bowel syndromeGastrointestinal disorders
AstheniaGeneral disorders
Chest painGeneral disorders
Oedema peripheralGeneral disorders
Abscess limbInfections and infestations
Bacterial sepsisInfections and infestations
COVID-19Infections and infestations
COVID-19 pneumoniaInfections and infestations
Device related infectionInfections and infestations
Escherichia pyelonephritisInfections and infestations
GastroenteritisInfections and infestations
GonorrhoeaInfections and infestations
Other adverse events (47 terms — click to expand)

ReactionSystemPlacebo/EculizumabEculizumab/EculizumabEculizumab (Combined Total)
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
Urinary tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
InfluenzaInfections and infestations
PyrexiaGeneral disorders
Back painMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
ContusionInjury, poisoning and procedural complications
Muscle spasmsMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
CystitisInfections and infestations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Oral herpesInfections and infestations
DizzinessNervous system disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
BronchitisInfections and infestations
HypoaesthesiaNervous system disorders
DyspepsiaGastrointestinal disorders
ToothacheGastrointestinal disorders
Thermal burnInjury, poisoning and procedural complications
ParaesthesiaNervous system disorders
InsomniaPsychiatric disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Dental cariesGastrointestinal disorders
Oedema peripheralGeneral disorders
Peripheral swellingGeneral disorders
Herpes zosterInfections and infestations
PharyngitisInfections and infestations
Muscular weaknessMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
AsthmaRespiratory, thoracic and mediastinal disorders
PeriodontitisInfections and infestations

Most-reported serious reactions: Urinary tract infection, Neuromyelitis optica spectrum disorder, Cholecystitis acute, Optic neuritis, Pneumonia, Pyelonephritis acute, Urosepsis, Femoral neck fracture.

Data from ClinicalTrials.gov NCT02003144 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Outcome prediction models in AQP4-IgG positive neuromyelitis optica spectrum disorders.
    Palace J, Lin DY, Zeng D, Majed M, et al · · 2019 · cited 160× · PMID 30938427 · DOI 10.1093/brain/awz054
  2. Targeting the complement system for the management of retinal inflammatory and degenerative diseases.
    Xu H, Chen M. · · 2016 · cited 129× · PMID 26948311 · DOI 10.1016/j.ejphar.2016.03.001
  3. Long-Term Safety and Efficacy of Eculizumab in Aquaporin-4 IgG-Positive NMOSD.
    Wingerchuk DM, Fujihara K, Palace J, Berthele A, et al · · 2021 · cited 74× · PMID 33586143 · DOI 10.1002/ana.26049
  4. Eculizumab: A Review in Neuromyelitis Optica Spectrum Disorder.
    Frampton JE. · · 2020 · cited 47× · PMID 32266705 · DOI 10.1007/s40265-020-01297-w
  5. Eculizumab monotherapy for NMOSD: Data from PREVENT and its open-label extension.
    Pittock SJ, Fujihara K, Palace J, Berthele A, et al · · 2022 · cited 46× · PMID 34498507 · DOI 10.1177/13524585211038291
  6. The role of the complement system in Multiple Sclerosis: A review.
    Saez-Calveras N, Stuve O. · · 2022 · cited 33× · PMID 36032156 · DOI 10.3389/fimmu.2022.970486
  7. Treatment of Rare Inflammatory Kidney Diseases: Drugs Targeting the Terminal Complement Pathway.
    Anliker-Ort M, Dingemanse J, van den Anker J, Kaufmann P. · · 2020 · cited 33× · PMID 33362783 · DOI 10.3389/fimmu.2020.599417
  8. Precision Medicine in Neurology: The Inspirational Paradigm of Complement Therapeutics.
    Gavriilaki M, Kimiskidis VK, Gavriilaki E. · · 2020 · cited 21× · PMID 33114553 · DOI 10.3390/ph13110341

Verify or expand the search:

Other trials of eculizumab

Trials testing the same drug.

Other recruiting trials for Neuromyelitis Optica

Currently open trials in the same condition.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02003144.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing