Brief Summary
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.
Brief Title
A Randomized Controlled Trial of Eculizumab in AQP4 Antibody-positive Participants With NMO (PREVENT Study)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Neuromyelitis Optica
Neuromyelitis Optica Spectrum Disorder
Eligibility Criteria
Key Inclusion Criteria:
1. Male or female participants ≥ 18 years old.
2. Diagnosis of NMO or NMOSD.
3. AQP4 antibody seropositive.
4. Historical relapse of at least 2 relapses in the last 12 months or 3 relapses in the last 24 months with at least 1 relapse in the 12 months prior to the screening.
5. Expanded Disability Status Scale score ≤ 7.
6. If a participant entered the study receiving immunosuppressive therapy (IST) for relapse prevention, the participant must have been on a stable maintenance dose of IST(s), as defined by the treating physician, prior to Screening and must have remained on that dose for the duration of the study, unless the participant experienced a relapse.
7. Female participants of childbearing potential were to have a negative pregnancy test (serum human chorionic gonadotropin). Participants were required to practice an effective, reliable, and medically approved contraceptive regimen during the study and for up to 5 months following discontinuation of treatment.
Key Exclusion Criteria:
1. Use of rituximab within 3 months prior to Screening.
2. Use of mitoxantrone within 3 months prior to Screening.
3. Use of intravenous immunoglobulin within 3 weeks prior to Screening.
1. Male or female participants ≥ 18 years old.
2. Diagnosis of NMO or NMOSD.
3. AQP4 antibody seropositive.
4. Historical relapse of at least 2 relapses in the last 12 months or 3 relapses in the last 24 months with at least 1 relapse in the 12 months prior to the screening.
5. Expanded Disability Status Scale score ≤ 7.
6. If a participant entered the study receiving immunosuppressive therapy (IST) for relapse prevention, the participant must have been on a stable maintenance dose of IST(s), as defined by the treating physician, prior to Screening and must have remained on that dose for the duration of the study, unless the participant experienced a relapse.
7. Female participants of childbearing potential were to have a negative pregnancy test (serum human chorionic gonadotropin). Participants were required to practice an effective, reliable, and medically approved contraceptive regimen during the study and for up to 5 months following discontinuation of treatment.
Key Exclusion Criteria:
1. Use of rituximab within 3 months prior to Screening.
2. Use of mitoxantrone within 3 months prior to Screening.
3. Use of intravenous immunoglobulin within 3 weeks prior to Screening.
Inclusion Criteria
Inclusion Criteria:
1. Male or female participants ≥ 18 years old.
2. Diagnosis of NMO or NMOSD.
3. AQP4 antibody seropositive.
4. Historical relapse of at least 2 relapses in the last 12 months or 3 relapses in the last 24 months with at least 1 relapse in the 12 months prior to the screening.
5. Expanded Disability Status Scale score ≤ 7.
6. If a participant entered the study receiving immunosuppressive therapy (IST) for relapse prevention, the participant must have been on a stable maintenance dose of IST(s), as defined by the treating physician, prior to Screening and must have remained on that dose for the duration of the study, unless the participant experienced a relapse.
7. Female participants of childbearing potential were to have a negative pregnancy test (serum human chorionic gonadotropin). Participants were required to practice an effective, reliable, and medically approved contraceptive regimen during the study and for up to 5 months following discontinuation of treatment.
1. Male or female participants ≥ 18 years old.
2. Diagnosis of NMO or NMOSD.
3. AQP4 antibody seropositive.
4. Historical relapse of at least 2 relapses in the last 12 months or 3 relapses in the last 24 months with at least 1 relapse in the 12 months prior to the screening.
5. Expanded Disability Status Scale score ≤ 7.
6. If a participant entered the study receiving immunosuppressive therapy (IST) for relapse prevention, the participant must have been on a stable maintenance dose of IST(s), as defined by the treating physician, prior to Screening and must have remained on that dose for the duration of the study, unless the participant experienced a relapse.
7. Female participants of childbearing potential were to have a negative pregnancy test (serum human chorionic gonadotropin). Participants were required to practice an effective, reliable, and medically approved contraceptive regimen during the study and for up to 5 months following discontinuation of treatment.
Gender
All
Gender Based
false
Keywords
Neuromyelitis Optica
Neuromyelitis Optica Spectrum Disorder
Devic's disease, Transverse Myelitis
Optic Neuritis
relapse
eculizumab
soliris
NMO-IgG
CNS Autoimmune Disorders
Demyelinating Disorders
NMO
NMOSD
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01892345
Org Class
Industry
Org Full Name
Alexion Pharmaceuticals, Inc.
Org Study Id
ECU-NMO-301
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Trial to Evaluate the Safety and Efficacy of Eculizumab in Patients With Relapsing Neuromyelitis Optica (NMO)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Participants With An Adjudicated On-trial Relapse
Outcome Time Frame
Baseline, Up To 211 Weeks (End of Study)
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Baseline, Up To 211 Weeks (End of Study)
Outcome Measure
Adjudicated On-trial Annualized Relapse Rate (ARR)
Outcome Description
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.
Outcome Time Frame
Baseline, Up To 211 Weeks (End of Study)
Outcome Measure
Change From Baseline In EDSS At End Of Study
Outcome Description
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.
Outcome Time Frame
Baseline, Up To 211 Weeks (End of Study)
Outcome Measure
Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study
Outcome Description
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.
Outcome Time Frame
Baseline, Up To 211 Weeks (End of Study)
Outcome Measure
Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study
Outcome Description
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.
Outcome Time Frame
Baseline, Up To 211 Weeks (End of Study)
Outcome Measure
Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At End Of Study
Outcome Description
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.
Outcome Time Frame
Baseline, Up To 211 Weeks (End of Study)
Outcome Measure
Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jerome Graber
Investigator Email
jgraber@montefiore.org
Investigator Phone
718-920-5505