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

Phase 3

Terminated

Conditions: Neuromyelitis Optica Spectrum Disorder
Neuromyelitis Optica

Interventions: Drug: Eculizumab
Drug: Placebo

Registration Number: NCT01892345

Lead Sponsor: Alexion Pharmaceuticals, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 143

Inclusion Criteria

Male or female participants ≥ 18 years old.
Diagnosis of NMO or NMOSD.
AQP4 antibody seropositive.
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.
Expanded Disability Status Scale score ≤ 7.
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.
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

Use of rituximab within 3 months prior to Screening.
Use of mitoxantrone within 3 months prior to Screening.
Use of intravenous immunoglobulin within 3 weeks prior to Screening.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Eculizumab	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	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.

Primary Outcome Measures

Name	Time	Method
Participants With An Adjudicated On-trial Relapse	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.

Secondary Outcome Measures

Name	Time	Method
Adjudicated On-trial Annualized Relapse Rate (ARR)	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.
Change From Baseline In EDSS At End Of Study	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.
Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study	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.
Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study	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.
Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At End Of Study	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.
Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study	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.

Trial Locations

Locations (70): John Hopkins University School of Medicine
🇺🇸
Baltimore, Maryland, United States
University of Sydney, Brain and Mind Center
🇦🇺
Camperdown, New South Wales, Australia
St. Vincent's Hospital Melbourne
🇦🇺
Fitzroy, Victoria, Australia
Hospital of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Vseobecna fakultni nemocnice Neurologicka klinika
🇨🇿
Praha, Czechia
Multiple Sclerosis Treatment Center of Dallas
🇺🇸
Dallas, Texas, United States
Klinikum rechts der Isar der TU Muenchen, Neurologische Klinik und Poliklinik
🇩🇪
Munich, Bayern, Germany
The Research Center of Southern California
🇺🇸
Carlsbad, California, United States
University of Maryland Medical Center
🇺🇸
Baltimore, Maryland, United States
Neurological Services of Orlando
🇺🇸
Orlando, Florida, United States
Mayo Clinic - Rochester
🇺🇸
Rochester, Minnesota, United States
Fort Wayne Neurological Center
🇺🇸
Fort Wayne, Indiana, United States
Multiple Sclerosis Comprehensive Care Center, NYU Langone Medical Center
🇺🇸
New York, New York, United States
Universitaria Policlinico di Catania
🇮🇹
Catania, Italy
Baptist Health Lexington
🇺🇸
Lexington, Kentucky, United States
Universitaetsmedizin Rostock, Klinik für Neurologie
🇩🇪
Rostock, Germany
Navamindradhiraj University, Vajira Hospital
🇹🇭
Dusit, Thailand
Azienda Ospedaliera Universitaria Federico II
🇮🇹
Napoli, Italy
Severance Hospital, Yonsei University
🇰🇷
Seoul, Korea, Republic of
The Walton Centre
🇬🇧
Liverpool, United Kingdom
FSBHI 'Siberian Clinical Center of FMBA'
🇷🇺
Krasnoyarsk, Russian Federation
Kyoto Min-iren Chuo Hospital
🇯🇵
Kyoto-shi, Kyoto, Japan
Universitaetsklinikum Heidelberg, Abteilung Neuroonkologie
🇩🇪
Heidelberg, Baden Wuerttemberg, Germany
Hospital General de Agudos Juan Antonio Fernandez
🇦🇷
Ciudad Autonoma, Buenos Aires, Buenos Aires, Argentina
Hyogo College of Medicine Hospital
🇯🇵
Nishinomiya-shi, Hyogo, Japan
Clinical Hospital Centre Zagreb
🇭🇷
Zagreb, Croatia
Republican Clinical Hospital for Rehabilitation of Healthcare Ministry of Republic of Tatarstan
🇷🇺
Kazan, Russian Federation
Hospital Universitario Austral
🇦🇷
Pilar, Buenos Aires, Argentina
The Ohio State University, Wexner Medical Center, CarePoint at Gahanna
🇺🇸
Gahanna, Ohio, United States
Hacettepe University Medical Faculty
🇹🇷
Ankara, Turkey
Dokuz Eylul University Medicine Faculty
🇹🇷
Izmir, Turkey
Yamaguchi University Hospital
🇯🇵
Ube-shi, Yamaguchi, Japan
Seoul University National Hospital
🇰🇷
Seoul, Korea, Republic of
First Pavlov State Medical University of St.Petersburg
🇷🇺
St. Petersburg, Russian Federation
Hospital Universitario Reina Sofia
🇪🇸
Cordoba, Spain
Hospital Universitario Clinico San Carlos
🇪🇸
Madrid, Spain
Hospital de Cruces
🇪🇸
Barakaldo, Bizkaia, Spain
Cheng Hsin General Hospital
🇨🇳
Taipei, Taiwan
SBEIHPE "Rostov SMU of MoH of RF"
🇷🇺
Rostov-on Don, Russian Federation
Korea University Anam Hospital
🇰🇷
Seoul, Korea, Republic of
University of Miami McKnight Brain Institute
🇺🇸
Miami, Florida, United States
University of Utah Health Care
🇺🇸
Salt Lake City, Utah, United States
Swedish Neuroscience Institute
🇺🇸
Seattle, Washington, United States
Århus Universitetshospital
🇩🇰
Århus, Denmark
Azienda Ospedaliera San Camillo Forlanini
🇮🇹
Rome, Italy
Neurological Centre of Latium Dipartimento di Neuroscienze
🇮🇹
Rome, Italy
Istanbul University Cerrahpasa Medical Faculty
🇹🇷
Istanbul, Turkey
Kocaeli University Medical Faculty
🇹🇷
Kocaeli, Turkey
National Center Hospital, NCNP
🇯🇵
Tokio, Japan
National Cancer Center
🇰🇷
Goyang-si, Gyeonggi-do, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
Hospital J. M. Ramos Mejia
🇦🇷
Ciudad Autonoma, Buenos Aires, Buenos Aires, Argentina
Georgetown University Hospital
🇺🇸
Washington, District of Columbia, United States
University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Chiba University Hospital
🇯🇵
Chiba-shi, Chiba, Japan
Kyushu University Hospital
🇯🇵
Fukuoka, Japan
Tohoku University Hospital
🇯🇵
Sendai-shi, Miyagi, Japan
Federal State Budget Institution of Healthcare - Siberian District Medical Center of FMBA of Russia
🇷🇺
Novosibirsk, Russian Federation
Ondokuz Mayis Univ. Med. Fac.
🇹🇷
Samsun, Turkey
Istanbul Bilim Universty Medical Fac.
🇹🇷
Istanbul, Turkey
John Radcliffe Hospital
🇬🇧
Oxford, United Kingdom
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Tokyo Medical and Dental University
🇯🇵
Bunkyo-ku, Tokyo, Japan
Hospital Kuala Lumpur
🇲🇾
Kuala Lumpur, Malaysia
Sunprasitthiprasong Hospital
🇹🇭
Ubon Ratchathani, Thailand
Thammasat University Hospital
🇹🇭
Pathumthani, Thailand
Fundacion Rosarina de Neuro Rehabilitacion
🇦🇷
Rosario, Santa Fe, Argentina
Mayo Clinic Arizona
🇺🇸
Scottsdale, Arizona, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States
Prince of Wales Hospital
🇭🇰
Shatin, Hong Kong