Clinical trial NCT01892345: A Randomized Controlled Trial of Eculizumab in AQP4 Antibody-positive Participants With NMO (PREVENT Study)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Neuromyelitis Optica
Neuromyelitis Optica Spectrum Disorder
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
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-04
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Participants With An Adjudicated On-trial Relapse
timeFrame: Baseline, Up To 211 Weeks (End of Study)
Secondary outcomes:
measure: Adjudicated On-trial Annualized Relapse Rate (ARR)
timeFrame: Baseline, Up To 211 Weeks (End of Study)
measure: Change From Baseline In EDSS At End Of Study
timeFrame: Baseline, Up To 211 Weeks (End of Study)
measure: Change From Baseline In Modified Rankin Scale (mRS) Score At End Of Study
timeFrame: Baseline, Up To 211 Weeks (End of Study)
measure: Change From Baseline In Hauser Ambulation Index (HAI) Score At End of Study
timeFrame: Baseline, Up To 211 Weeks (End of Study)
measure: Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At End Of Study
timeFrame: Baseline, Up To 211 Weeks (End of Study)
measure: Change From Baseline In EuroQoL EQ-5D Index Score At End Of Study
timeFrame: Baseline, Up To 211 Weeks (End of Study)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Carlsbad
country: United States
facility: The Research Center of Southern California
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Miami
country: United States
facility: University of Miami McKnight Brain Institute
state: Florida
city: Orlando
country: United States
facility: Neurological Services of Orlando
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: John Hopkins University School of Medicine
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Multiple Sclerosis Comprehensive Care Center, NYU Langone Medical Center
state: New York
city: Gahanna
country: United States
facility: The Ohio State University, Wexner Medical Center, CarePoint at Gahanna
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: Multiple Sclerosis Treatment Center of Dallas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Care
state: Utah
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Ciudad Autonoma, Buenos Aires
country: Argentina
facility: Hospital General de Agudos Juan Antonio Fernandez
state: Buenos Aires
city: Ciudad Autonoma, Buenos Aires
country: Argentina
facility: Hospital J. M. Ramos Mejia
state: Buenos Aires
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
state: Buenos Aires
city: Rosario
country: Argentina
facility: Fundacion Rosarina de Neuro Rehabilitacion
state: Santa Fe
city: Camperdown
country: Australia
facility: University of Sydney, Brain and Mind Center
state: New South Wales
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice Neurologicka klinika
city: Århus
country: Denmark
facility: Århus Universitetshospital
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg, Abteilung Neuroonkologie
state: Baden Wuerttemberg
city: Munich
country: Germany
facility: Klinikum rechts der Isar der TU Muenchen, Neurologische Klinik und Poliklinik
state: Bayern
city: Rostock
country: Germany
facility: Universitaetsmedizin Rostock, Klinik für Neurologie
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Catania
country: Italy
facility: Universitaria Policlinico di Catania
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Rome
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Rome
country: Italy
facility: Neurological Centre of Latium Dipartimento di Neuroscienze
city: Chiba-shi
country: Japan
facility: Chiba University Hospital
state: Chiba
city: Nishinomiya-shi
country: Japan
facility: Hyogo College of Medicine Hospital
state: Hyogo
city: Kyoto-shi
country: Japan
facility: Kyoto Min-iren Chuo Hospital
state: Kyoto
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Bunkyo-ku
country: Japan
facility: Tokyo Medical and Dental University
state: Tokyo
city: Ube-shi
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Tokio
country: Japan
facility: National Center Hospital, NCNP
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul University National Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kazan
country: Russian Federation
facility: Republican Clinical Hospital for Rehabilitation of Healthcare Ministry of Republic of Tatarstan
city: Krasnoyarsk
country: Russian Federation
facility: FSBHI 'Siberian Clinical Center of FMBA'
city: Novosibirsk
country: Russian Federation
facility: Federal State Budget Institution of Healthcare - Siberian District Medical Center of FMBA of Russia
city: Rostov-on Don
country: Russian Federation
facility: SBEIHPE "Rostov SMU of MoH of RF"
city: St. Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of St.Petersburg
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Bizkaia
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Taipei
country: Taiwan
facility: Cheng Hsin General Hospital
city: Dusit
country: Thailand
facility: Navamindradhiraj University, Vajira Hospital
city: Pathumthani
country: Thailand
facility: Thammasat University Hospital
city: Ubon Ratchathani
country: Thailand
facility: Sunprasitthiprasong Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul Bilim Universty Medical Fac.
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medicine Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayis Univ. Med. Fac.
city: Liverpool
country: United Kingdom
facility: The Walton Centre
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.