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

Neuromyelitis Optica Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01892345
• Other study ID #: ECU-NMO-301
• Status: Terminated
• Phase: Phase 3
• Start date: April 11, 2014
• Est. completion date: July 17, 2018

Study information

• Verified date: June 2019
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 143
• Est. completion date: July 17, 2018
• Est. primary completion date: July 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neuromyelitis Optica
• Neuromyelitis Optica Spectrum Disorder

Intervention

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
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Croatia,  Czechia,  Denmark,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants With An Adjudicated On-trial Relapse	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	Adjudicated On-trial Annualized Relapse Rate (ARR)	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)
Secondary	Change From Baseline In EDSS At 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)
Secondary	Change From Baseline In Modified Rankin Scale (mRS) Score At 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)
Secondary	Change From Baseline In Hauser Ambulation Index (HAI) Score At 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)
Secondary	Change From Baseline In European Quality Of Life (EuroQoL) Health 5-Dimension Questionnaire (EQ-5D) Visual Analogue Scale At 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)
Secondary	Change From Baseline In EuroQoL EQ-5D Index Score At 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)

External Links

•   Alexion Clinical Trials Website