Neuromyelitis Optica Spectrum Disorders, NMOSD
Conditions
Keywords
NMOSD, Neuromyelitis Optica Spectrum Disorders, eculizumab, anti-AQP4
Brief summary
The primary objective of this study is to evaluate the efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of Eculizumab in Chinese Adults with Neuromyelitis Optica Spectrum Disorders (NMOSD).
Interventions
DRUGeculizumab
Participants will receive eculizumab by intravenous (IV) infusion for 52 weeks.
Sponsors
AstraZeneca
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Participants with diagnosis of NMOSD as defined by the 2015 international consensus diagnostic criteria * Anti-AQP4 antibody positive * At least 1 attack or relapse in the last 12 months prior to the Screening Period * EDSS score ≤ 7 * If a participant enters the study receiving IST(s) for relapse prevention, the participant must be on a stable maintenance dose of IST(s) as follows, prior to screening and must remain on that dose for the duration of the study, unless the participant experiences a relapse * Female participants of childbearing potential must have a negative pregnancy test (serum HCG at screening * Male participants are eligible to participate if they agree to the following during the study intervention Treatment Period and for at least 5 months after the last dose of study intervention: * Refrain from donating fresh unwashed semen. PLUS, either, * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR * Must agree to use barrier as detailed below: * Agree to use a male condom when having sexual intercourse with a WOCBP who is not currently pregnant.
Exclusion criteria
* Pregnant, breastfeeding, or intending to conceive during the course of the study * Prior history of N meningitidis infection or unresolved meningococcal disease * Any systemic bacterial or other infection which is clinically significant in the opinion of the Investigator and has not been treated with appropriate antibiotics * Presence of fever ≥ 38 C within 7 days prior to study intervention administration on Day 1 * Hypersensitivity to murine proteins or to one of the excipients of study intervention * Use of rituximab, inebilizumab, or other B cell-depleting therapy within 6 months prior to Day 1 and during the study * Use of mitoxantrone or satralizumab within 3 months prior to screening and during the study * Use of IVIg within 3 weeks prior to screening * If a participant enters the study receiving oral corticosteroid(s) with or without other ISTs, the daily corticosteroid dose must be no more than prednisone 20 mg/day (or equivalent) prior to screening and the participant must remain on that dose for the duration of the study or until the participant experiences a relapse (specific medications listed in Section 6.9.1 may be allowed) * Has previously received treatment with C5 inhibitors * Participation in any other investigational drug study or exposure to an investigational drug or device within 5 half-lives of treatment (if known) or 30 days, which is longer, before the first dose administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The efficacy of eculizumab in anti-AQP4 antibody positive participants with NMOSD measured by Adjudicated On-trial annualized relapse rate (ARR). | Baseline through Week 52 | The mean (95% Confidence Interval) of patient-level Adjudicated On-trial annualized relapse rate (ARR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The efficacy of eculizumab by assessing change from baseline to end of study in Ambulatory Function as Measured by Hauser Ambulation Index (HAI) | Baseline through Week 52 | Intercurrent Event (ICE): * ICE1: Premature discontinuation of study intervention * ICE2: Initiation of disallowed therapy or medicine * Summary measure: The mean (95% Confidence Interval) change from baseline to end of study in ambulatory function as measured by Hauser ambulation index (HAI) |
| The efficacy of eculizumab by assessing change from baseline to end of study in European Quality of Life 5-Dimension Questionnaire (EQ-5D) Index Score | Baseline through Week 52 | Intercurrent Event (ICE): * ICE1: Premature discontinuation of study intervention * ICE2: Initiation of disallowed therapy or medicine * Summary measure: The mean (95% Confidence Interval) change from baseline to end of study in EQ-5D index score |
| Change From Baseline to end of study in EQ-5D Visual Analogue Scale (VAS) Score | Baseline through Week 52 | Intercurrent Event (ICE): * ICE1: Premature discontinuation of study intervention * ICE2: Initiation of disallowed therapy or medicine * Summary measure: The mean (95% Confidence Interval) change from baseline to end of study in EQ-5D VAS |
| The efficacy of eculizumab by assessing change from baseline to end of study in Expanded Disability Status Scale (EDSS) Score | Baseline through Week 52 | Intercurrent Event (ICE): * ICE1: Premature discontinuation of study intervention * ICE2: Initiation of disallowed therapy or medicine * Summary measure: The mean (95% Confidence Interval) change from baseline to end of study in EDSS score |
| Serum Free Complement Component 5 (C5) Concentrations Over Time | Baseline through Week 52 | Intercurrent Event (ICE): * ICE1: Premature discontinuation of study intervention * ICE2: Initiation of disallowed therapy or medicine * Summary measure: Mean changes in serum free C5 concentrations at all scheduled visits |
| Number of Treatment-emergent Antidrug Antibody (ADA) Positive Participants | Baseline through Week 52 | Intercurrent Event (ICE): * ICE1: Premature discontinuation of study intervention * ICE2: Initiation of disallowed therapy or medicine * Summary measure: Proportion of treatment-emergent ADA positive participants |
| To characterize the overall safety of eculizumab in the treatment of NMOSD | Baseline through Week 52 | Number of participants with TEAEs, SAEs, and TEAEs leading to study intervention discontinuation, with abnormal vital signs, abnormal ECG readings, and abnormal laboratory tests results |
| Serum Eculizumab Concentrations Over Time | Baseline through Week 52 | Intercurrent Event (ICE): * ICE1: Premature discontinuation of study intervention * ICE2: Initiation of disallowed therapy or medicine * Summary measure: Mean serum eculizumab concentrations at all scheduled visits |
Countries
China
Outcome results
None listed