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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01892345
Registration number
NCT01892345
Ethics application status
Date submitted
20/06/2013
Date registered
4/07/2013
Date last updated
26/06/2019
Titles & IDs
Public title
A Randomized Controlled Trial of Eculizumab in AQP4 Antibody-positive Participants With NMO (PREVENT Study)
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Scientific 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)
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Secondary ID [1]
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ECU-NMO-301
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Neuromyelitis Optica
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Neuromyelitis Optica Spectrum Disorder
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Condition category
Condition code
Inflammatory and Immune System
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Autoimmune diseases
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Neurological
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Other neurological disorders
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Eye
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Diseases / disorders of the eye
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Eculizumab
Treatment: Drugs - Placebo
Experimental: Eculizumab - 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.
Placebo comparator: Placebo - 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.
Treatment: Drugs: Eculizumab
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
Treatment: Drugs: Placebo
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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Participants With An Adjudicated On-trial Relapse
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Up To 211 Weeks (End of Study)
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Secondary outcome [1]
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Adjudicated On-trial Annualized Relapse Rate (ARR)
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Up To 211 Weeks (End of Study)
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Secondary outcome [2]
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Change From Baseline In EDSS At End Of Study
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline, Up To 211 Weeks (End of Study)
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Secondary outcome [3]
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Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study
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Assessment method [3]
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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.
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Timepoint [3]
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Baseline, Up To 211 Weeks (End of Study)
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Secondary outcome [4]
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Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study
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Assessment method [4]
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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.
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Timepoint [4]
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Baseline, Up To 211 Weeks (End of Study)
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Secondary outcome [5]
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Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At End Of Study
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Assessment method [5]
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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.
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Timepoint [5]
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Baseline, Up To 211 Weeks (End of Study)
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Secondary outcome [6]
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Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study
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Assessment method [6]
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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.
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Timepoint [6]
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Baseline, Up To 211 Weeks (End of Study)
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Eligibility
Key inclusion criteria
Key
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.
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Minimum age
18
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
11/04/2014
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Date of last participant enrolment
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Actual
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Date of last data collection
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Actual
17/07/2018
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Sample size
Target
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Accrual to date
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Final
143
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
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University of Sydney, Brain and Mind Center - Camperdown
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Recruitment hospital [2]
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St. Vincent's Hospital Melbourne - Fitzroy
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2050 - Camperdown
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Recruitment postcode(s) [2]
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3065 - Fitzroy
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Recruitment outside Australia
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Funding & Sponsors
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Name
Alexion Pharmaceuticals, Inc.
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT01892345
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Trial related presentations / publications
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. Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, Nakashima I, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Fujita KP, Armstrong R, Wingerchuk DM. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019 Aug 15;381(7):614-625. doi: 10.1056/NEJMoa1900866. Epub 2019 May 3. Singh P, Gao X, Kleijn HJ, Bellanti F, Pelto R. Eculizumab Pharmacokinetics and Pharmacodynamics in Patients With Neuromyelitis Optica Spectrum Disorder. Front Neurol. 2021 Nov 3;12:696387. doi: 10.3389/fneur.2021.696387. eCollection 2021. 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. 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. Palace J, Wingerchuk DM, Fujihara K, Berthele A, Oreja-Guevara C, Kim HJ, Nakashima I, Levy M, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Yountz M, Miller L, Armstrong R, Pittock S; PREVENT Study Group. Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial. Mult Scler Relat Disord. 2021 Jan;47:102641. doi: 10.1016/j.msard.2020.102641. Epub 2020 Nov 26.
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Public notes
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Contacts
Principal investigator
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No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/45/NCT01892345/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/45/NCT01892345/SAP_001.pdf
Results publications and other study-related documents
Type
Citations or Other Details
Journal
Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M...
[
More Details
]
Results are available at
https://clinicaltrials.gov/study/NCT01892345
Download to PDF