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

Study Timeline

• Study First Submitted: 2013-06-20
• Study First Submitted QC: 2013-07-01
• Study First Posted: 2013-07-04
• Study Start: 2014-04-11
• Primary Completion: 2018-07-17
• Study Completion: 2018-07-17
• Status Verified: 2019-06
• Results First Submitted: 2019-06-07
• Results First Submitted QC: 2019-06-07
• Last Update Submitted: 2019-06-07
• Results First Posted: 2019-06-26
• Last Update Posted: 2019-06-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 143

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 & 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)

Mayo Clinic Arizona; 🇺🇸 Scottsdale, Arizona, United States

The Research Center of Southern California; 🇺🇸 Carlsbad, California, United States

Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

University of Miami McKnight Brain Institute; 🇺🇸 Miami, Florida, United States

Neurological Services of Orlando; 🇺🇸 Orlando, Florida, United States

Fort Wayne Neurological Center; 🇺🇸 Fort Wayne, Indiana, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

Baptist Health Lexington; 🇺🇸 Lexington, Kentucky, United States

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

John Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States

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