A Phase 3 interventional study of Eculizumab and Placebo in Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorder, sponsored by Alexion Pharmaceuticals, Inc.. Terminated at 70 sites in 18 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-06-26.
Sponsored by Alexion Pharmaceuticals, Inc. (part of AstraZeneca) · Phase 3, Interventional, and Treatment
The objectives of this time-to-event study were to assess the efficacy and safety of eculizumab as compared with placebo in participants with neuromyelitis optica spectrum disorder (NMOSD) who were anti-aquaporin-4 (AQP4) antibody-positive.
168 studies on the registry are indexed under Neuromyelitis Optica; 72 are open to participants now.
This study's enrollment of 143 is above the median of 26 across 100 interventional studies indexed under Neuromyelitis Optica.
Browse Neuromyelitis Optica studies →Alexion Pharmaceuticals, Inc. is the lead sponsor of 255 studies on the registry; 24 are open to participants now.
Of its 101 completed or terminated interventional studies of FDA-regulated products, 73 (72%) have results posted.
First submitted before Alexion Pharmaceuticals, Inc. became part of AstraZeneca.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Biological/Vaccine: Eculizumab; Induction Period: Participants received eculizumab (900 milligrams \[mg\]) via intravenous (IV) infusion once a week (every 7 ± 2 days) for 4 weeks followed by eculizumab 1200 mg for the fifth dose (Week 4). This was followed by the Maintenance Period: Participants received eculizumab (1200 mg) via IV infusion every 2 weeks (every 14 ± 2 days) from the sixth dose (Week 6) onwards.
Drug: Eculizumab
Placebo contains the same buffer components without the active ingredient. Induction Period: Participants received matching placebo (900 mg) via IV infusion once a week (every 7 ± 2 days) for 4 weeks, followed by matching placebo (1200 mg) for the fifth dose (Week 4). This was followed by the Maintenance Period: Participants received matching placebo (1200 mg) via IV infusion every 2 weeks (every 14 ± 2 days) from the sixth dose (Week 6) onwards.
Drug: Placebo
Induction Phase: 900 mg IV weekly for 4 weeks, followed by 1200 mg for the fifth dose; Maintenance Phase: 1200 mg IV every 2 weeks
Also known as: Soliris
Induction Phase: matching placebo (900 mg) IV weekly for 4 weeks, followed by matching placebo (1200 mg) for the fifth dose; Maintenance Phase: matching placebo (1200 mg) IV every 2 weeks
Participants With An Adjudicated On-trial Relapse
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. An adjudicated On-trial Relapse was defined by the protocol and positively adjudicated by the relapse adjudication committee.
Time frame: Baseline, Up To 211 Weeks (End of Study)
Adjudicated On-trial Annualized Relapse Rate (ARR)
The adjudicated On-trial ARR was computed as the total number of relapses divided by the total number of patient years in the study period. A central independent committee was used to adjudicate all On-trial Relapses as determined by the treating physician. Results reported as adjusted adjudicated On-trial ARR based on a Poisson regression adjusted for randomization strata and historical ARR in 24 months prior to Screening.
Time frame: Baseline, Up To 211 Weeks (End of Study)
Change From Baseline In EDSS At End Of Study
Disease-related disability was measured by the EDSS. 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.
Time frame: Baseline, Up To 211 Weeks (End of Study)
Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study
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 disability) to 6 (death) in whole-point increments. A decrease in score indicates improvement.
Time frame: Baseline, Up To 211 Weeks (End of Study)
Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study
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 ambulatory with no assistance) and 9 being the worst (restricted to wheel chair; unable to transfer self independently). A decrease in score indicates improvement.
Time frame: Baseline, Up To 211 Weeks (End of Study)
Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At End Of Study
The EuroQoL EQ-5D is a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. Assessments were made using the EQ-5D Visual Analogue Scale, which captures the self-rating of current health status using a visual "thermometer" with the endpoints of 100 (best imaginable health state) at the top and zero (worst imaginable health state) at the bottom. An increase in score indicates improvement.
Time frame: Baseline, Up To 211 Weeks (End of Study)
Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study
The EuroQoL EQ-5D is a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. Index scores range from less than 0 to 1, with higher scores representing a better health status.
Time frame: Baseline, Up To 211 Weeks (End of Study)
| Milestone | Eculizumab | Placebo |
|---|---|---|
| Started | 96 | 47 |
| Received at least 1 dose of study drug | 96 | 47 |
| Completed | 80 | 44 |
| Not completed | 16 | 3 |
| Withdrew: Adverse event | 0 | 2 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Lost to follow-up | 3 | 0 |
| Withdrew: Withdrawal by subject | 12 | 1 |
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. An adjudicated On-trial Relapse was defined by the protocol and positively adjudicated by the relapse adjudication committee.
| Participants | Eculizumab | Placebo |
|---|---|---|
| Participants With An Adjudicated On-trial Relapse | 3 | 20 |
The adjudicated On-trial ARR was computed as the total number of relapses divided by the total number of patient years in the study period. A central independent committee was used to adjudicate all On-trial Relapses as determined by the treating physician. Results reported as adjusted adjudicated On-trial ARR based on a Poisson regression adjusted for randomization strata and historical ARR in 24 months prior to Screening.
| relapses/years on study | Eculizumab | Placebo |
|---|---|---|
| Adjudicated On-trial Annualized Relapse Rate (ARR) | 0.016 (0.005 to 0.050) | 0.350 (0.199 to 0.616) |
Disease-related disability was measured by the EDSS. 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.
| units on a scale | Eculizumab | Placebo |
|---|---|---|
| Change From Baseline In EDSS At End Of Study | -0.18 ± 0.814 | 0.12 ± 0.945 |
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 disability) to 6 (death) in whole-point increments. A decrease in score indicates improvement.
| units on a scale | Eculizumab | Placebo |
|---|---|---|
| Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study | -0.2 ± 0.72 | 0.1 ± 0.75 |
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 ambulatory with no assistance) and 9 being the worst (restricted to wheel chair; unable to transfer self independently). A decrease in score indicates improvement.
| units on a scale | Eculizumab | Placebo |
|---|---|---|
| Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study | -0.4 ± 1.08 | 0.5 ± 1.61 |
The EuroQoL EQ-5D is a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. Assessments were made using the EQ-5D Visual Analogue Scale, which captures the self-rating of current health status using a visual "thermometer" with the endpoints of 100 (best imaginable health state) at the top and zero (worst imaginable health state) at the bottom. An increase in score indicates improvement.
| units on a scale | Eculizumab | Placebo |
|---|---|---|
| Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At End Of Study | 5.4 ± 18.53 | 0.6 ± 16.39 |
The EuroQoL EQ-5D is a generic, standardized, self-administered instrument that provides a simple, descriptive profile and a single index value for health status. Index scores range from less than 0 to 1, with higher scores representing a better health status.
| units on a scale | Eculizumab | Placebo |
|---|---|---|
| Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study | 0.05 ± 0.179 | -0.04 ± 0.212 |
Collected over From Day 1 to End of Study (211 Weeks). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Eculizumab | 1/96 (1%) | 30/96 (31.3%) | 86/96 (89.6%) |
| Placebo | 0/47 (0%) | 26/47 (55.3%) | 43/47 (91.5%) |
| Event | Eculizumab | Placebo |
|---|---|---|
| Neuromyelitis optica spectrum disorderNervous system disorders | 7/96 | 16/47 |
| PneumoniaInfections and infestations | 3/96 | 1/47 |
| PancytopeniaBlood and lymphatic system disorders | 0/96 | 1/47 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/96 | 1/47 |
| Myocardial ischaemiaCardiac disorders | 0/96 | 1/47 |
| VertigoEar and labyrinth disorders | 0/96 | 1/47 |
| Abdominal painGastrointestinal disorders | 0/96 | 1/47 |
| PancreatitisGastrointestinal disorders | 0/96 | 1/47 |
| Cholecystitis acuteHepatobiliary disorders | 1/96 | 1/47 |
| BronchitisInfections and infestations | 1/96 | 1/47 |
| Event | Eculizumab | Placebo |
|---|---|---|
| Upper respiratory tract infectionInfections and infestations | 28/96 | 6/47 |
| NauseaGastrointestinal disorders | 16/96 | 12/47 |
| HeadacheNervous system disorders | 22/96 | 11/47 |
| Urinary tract infectionInfections and infestations | 11/96 | 10/47 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 10/96 | 10/47 |
| NasopharyngitisInfections and infestations | 20/96 | 9/47 |
| VomitingGastrointestinal disorders | 9/96 | 8/47 |
| DiarrhoeaGastrointestinal disorders | 15/96 | 7/47 |
| CoughRespiratory, thoracic and mediastinal disorders | 10/96 | 7/47 |
| Back painMusculoskeletal and connective tissue disorders | 14/96 | 6/47 |
Full Analysis Set (FAS): all participants who were randomized to treatment and who received at least 1 dose of study drug.
| Age, Continuous(years) | Eculizumab | Placebo | Total |
|---|---|---|---|
| Mean | 43.9 ± 13.32 | 45.0 ± 13.29 | 44.3 ± 13.27 |
| Sex: Female, Male(Participants) | Eculizumab | Placebo | Total |
|---|---|---|---|
| Female | 88 | 42 | 130 |
| Male | 8 | 5 | 13 |
| Ethnicity (NIH/OMB)(Participants) | Eculizumab | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 13 | 3 | 16 |
| Not Hispanic or Latino | 78 | 41 | 119 |
| Unknown or Not Reported | 5 | 3 | 8 |
| Race/Ethnicity, Customized(Participants) | Eculizumab | Placebo | Total |
|---|---|---|---|
| Asian | 37 | 15 | 52 |
| Black or African American | 9 | 8 | 17 |
| White | 46 | 24 | 70 |
| Other or Unknown | 4 | 0 | 4 |
| Overall Stratification Groupings (4 strata) at Randomization(Participants) | Eculizumab | Placebo | Total |
|---|---|---|---|
| Low EDSS (≤ 2.0) | 11 | 5 | 16 |
| High EDSS (≥ 2.5 to ≤ 7) and Treatment Naive | 12 | 5 | 17 |
| High EDSS (≥ 2.5 to ≤ 7): Same IST | 44 | 22 | 66 |
| High EDSS (≥ 2.5 to ≤ 7): Change in IST | 29 | 15 | 44 |
Documents are hosted by the registry — open the source record to download them.
Ran from Apr 2014 to primary completion in Jul 2018, 51 months.
Results were first posted in Jun 2019, 11 months after primary completion.
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Studies of the drug tested here: Eculizumab
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