A Randomized Controlled Trial of Eculizumab in AQP4 Antibody-positive Participants With NMO (PREVENT Study)

June 7, 2019 updated by: Alexion Pharmaceuticals

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Trial to Evaluate the Safety and Efficacy of Eculizumab in Patients With Relapsing Neuromyelitis Optica (NMO)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

143

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
    • Buenos Aires
      • Ciudad Autonoma, Buenos Aires, Buenos Aires, Argentina, 1425
        • Hospital General de Agudos Juan Antonio Fernandez
      • Ciudad Autonoma, Buenos Aires, Buenos Aires, Argentina, C1221
        • Hospital J. M. Ramos Mejía
      • Pilar, Buenos Aires, Argentina, B1629ODT
        • Hospital Universitario Austral
    • Santa Fe
      • Rosario, Santa Fe, Argentina, S2000BZL
        • Fundacion Rosarina de Neuro Rehabilitacion
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • University of Sydney, Brain and Mind Center
    • Victoria
      • Fitzroy, Victoria, Australia, 3065
        • St. Vincent's Hospital Melbourne
  • Croatia
      • Zagreb, Croatia, 10000
        • Clinical Hospital Centre Zagreb
  • Czechia
      • Praha, Czechia, 128 21
        • Vseobecna fakultni nemocnice Neurologicka klinika
  • Denmark
      • Århus, Denmark, 8000
        • Århus Universitetshospital
  • Germany
      • Rostock, Germany, 18147
        • Universitaetsmedizin Rostock, Klinik für Neurologie
    • Baden Wuerttemberg
      • Heidelberg, Baden Wuerttemberg, Germany, 69120
        • Universitaetsklinikum Heidelberg, Abteilung Neuroonkologie
    • Bayern
      • Munich, Bayern, Germany, 81675
        • Klinikum rechts der Isar der TU Muenchen, Neurologische Klinik und Poliklinik
  • Hong Kong
      • Shatin, Hong Kong
        • Prince of Wales Hospital
  • Italy
      • Catania, Italy, 95123
        • Universitaria Policlinico di Catania
      • Napoli, Italy, 80131
        • Azienda Ospedaliera Universitaria Federico II
      • Rome, Italy, 00151
        • Azienda Ospedaliera San Camillo Forlanini
      • Rome, Italy, 00178
        • Neurological Centre of Latium Dipartimento di Neuroscienze
  • Japan
      • Fukuoka, Japan, 812-8582
        • Kyushu University Hospital
      • Tokio, Japan, 187-8551
        • National Center Hospital, NCNP
    • Chiba
      • Chiba-shi, Chiba, Japan, 260-8677
        • Chiba University Hospital
    • Hyogo
      • Nishinomiya-shi, Hyogo, Japan, 663-8501
        • Hyogo College of Medicine Hospital
    • Kyoto
      • Kyoto-shi, Kyoto, Japan, 604-8453
        • Kyoto Min-iren Chuo Hospital
    • Miyagi
      • Sendai-shi, Miyagi, Japan, 980-8574
        • Tohoku University Hospital
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8519
        • Tokyo Medical and Dental University
    • Yamaguchi
      • Ube-shi, Yamaguchi, Japan, 755-8505
        • Yamaguchi University Hospital
  • Korea, Republic of
      • Seoul, Korea, Republic of, 02841
        • Korea University Anam Hospital
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University
      • Seoul, Korea, Republic of, 03080
        • Seoul University National Hospital
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
        • National Cancer Center
  • Malaysia
      • Kuala Lumpur, Malaysia, 50586
        • Hospital Kuala Lumpur
  • Russian Federation
      • Kazan, Russian Federation, 420021
        • Republican Clinical Hospital for Rehabilitation of Healthcare Ministry of Republic of Tatarstan
      • Krasnoyarsk, Russian Federation, 630037
        • FSBHI 'Siberian Clinical Center of FMBA'
      • Novosibirsk, Russian Federation, 630067
        • Federal State Budget Institution of Healthcare - Siberian District Medical Center of FMBA of Russia
      • Rostov-on Don, Russian Federation, 344022
        • SBEIHPE "Rostov SMU of MoH of RF"
      • St. Petersburg, Russian Federation, 197022
        • First Pavlov State Medical University of St.Petersburg
  • Spain
      • Cordoba, Spain, 14011
        • Hospital Universitario Reina Sofia
      • Madrid, Spain, 28040
        • Hospital Universitario Clínico San Carlos
    • Bizkaia
      • Barakaldo, Bizkaia, Spain, 48903
        • Hospital De Cruces
  • Taiwan
      • Taipei, Taiwan, 112
        • Cheng Hsin General Hospital
  • Thailand
      • Dusit, Thailand, 10300
        • Navamindradhiraj University, Vajira Hospital
      • Pathumthani, Thailand, 12120
        • Thammasat University Hospital
      • Ubon Ratchathani, Thailand, 34000
        • Sunprasitthiprasong Hospital
  • Turkey
      • Ankara, Turkey, 06100
        • Hacettepe University Medical Faculty
      • Istanbul, Turkey, 34098
        • Istanbul University Cerrahpasa Medical Faculty
      • Istanbul, Turkey, 34381
        • Istanbul Bilim Universty Medical Fac.
      • Izmir, Turkey, 35340
        • Dokuz Eylul University Medicine Faculty
      • Kocaeli, Turkey, 41380
        • Kocaeli University Medical Faculty
      • Samsun, Turkey, 55139
        • Ondokuz Mayis Univ. Med. Fac.
  • United Kingdom
      • Liverpool, United Kingdom, L9 7LJ
        • The Walton Centre
      • Oxford, United Kingdom, OX3 9DU
        • John Radcliffe Hospital
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Arizona
    • California
      • Carlsbad, California, United States, 92011
        • The Research Center of Southern California
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Hospital
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami McKnight Brain Institute
      • Orlando, Florida, United States, 32806
        • Neurological Services of Orlando
    • Indiana
      • Fort Wayne, Indiana, United States, 46804
        • Fort Wayne Neurological Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Baptist Health Lexington
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
      • Baltimore, Maryland, United States, 21287
        • John Hopkins University School Of Medicine
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic - Rochester
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10016
        • Multiple Sclerosis Comprehensive Care Center, NYU Langone Medical Center
    • Ohio
      • Gahanna, Ohio, United States, 43230
        • The Ohio State University, Wexner Medical Center, CarePoint at Gahanna
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Texas
      • Dallas, Texas, United States, 75246
        • Multiple Sclerosis Treatment Center of Dallas
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Health Care
    • Washington
      • Seattle, Washington, United States, 98122
        • Swedish Neuroscience Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: 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
Other Names:
  • Soliris
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.
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participants With An Adjudicated On-trial Relapse
Time Frame: Baseline, Up To 211 Weeks (End of Study)
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.
Baseline, Up To 211 Weeks (End of Study)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adjudicated On-trial Annualized Relapse Rate (ARR)
Time Frame: Baseline, Up To 211 Weeks (End of Study)
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.
Baseline, Up To 211 Weeks (End of Study)
Change From Baseline In EDSS At End Of Study
Time Frame: Baseline, Up To 211 Weeks (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.
Baseline, Up To 211 Weeks (End of Study)
Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study
Time Frame: Baseline, Up To 211 Weeks (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.
Baseline, Up To 211 Weeks (End of Study)
Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study
Time Frame: Baseline, Up To 211 Weeks (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.
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
Time Frame: Baseline, Up To 211 Weeks (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.
Baseline, Up To 211 Weeks (End of Study)
Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study
Time Frame: Baseline, Up To 211 Weeks (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.
Baseline, Up To 211 Weeks (End of Study)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 11, 2014

Primary Completion (Actual)

July 17, 2018

Study Completion (Actual)

July 17, 2018

Study Registration Dates

First Submitted

June 20, 2013

First Submitted That Met QC Criteria

July 1, 2013

First Posted (Estimate)

July 4, 2013

Study Record Updates

Last Update Posted (Actual)

June 26, 2019

Last Update Submitted That Met QC Criteria

June 7, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ECU-NMO-301

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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