Efficacy of Bevacizumab (Avastin) in Treatment of Acute NMO Exacerbations
This is a phase 1b interventional trial of bevacizumab (Avastin®) to evaluate the tolerability/safety and preliminary efficacy of bevacizumab (Avastin®) as add-on therapy for treatment of acute optic neuritis and/or transverse myelitis in neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD). A single infusion of Avastin® is added to standard-of-care high dose steroids and an additional dose of Avastin® is added to plasma exchange (if necessary). The primary outcomes are clinical changes in the Expanded Disability Severity Scale, Timed 25-foot Walk and Low Contrast Visual Acuity, MRI parameters and safety.
Neuromyelitis Optica Spectrum Disorder
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label Phase 1b Study of Avastin® (Bevacizumab) for the Treatment of Acute Optic Neuritis and/or Transverse Myelitis in Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD).|
- Composite change in Expanded Disability Status Score (EDSS), Low Contrast Visual Acuity (LCVA) and Timed 25-Foot Walk [ Time Frame: 91 days ] [ Designated as safety issue: No ]
The EDSS provides a total score on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.
Low Contrast Visual Acuity: Low-contrast Sloan letter charts are readily available and provide a practical, quantitative, and standardized assessment of visual function. 2.5% low contrast visual acuity will be measured daily during the steroid phase and weekly during the plasma exchange phase, the day after a bevacizumab (Avastin®) infusion.
Timed 25-Foot Walk
Timed 25-foot walking trials will be assessed every day during the steroid phase and weekly in the plasma exchange phase, the day after a bevacizumab (Avastin®) infusion.
- Safety Assessment [ Time Frame: 91 days ] [ Designated as safety issue: Yes ]
- Frequency and severity of adverse events.
- Frequency of serious adverse events.
- Percentage of subjects withdrawing due to adverse events.
- Change from baseline in hematology, chemistry, and urinalysis parameters.
- MRI changes [ Time Frame: 91 days ] [ Designated as safety issue: No ]MRIs will be performed for standard of care purposes and will be used to make clinical decisions about escalation of immunosuppressive treatment. For this study, the MRIs will also be analyzed for two parameters: length of T2 hyperintensity in the spinal cord and optic nerve and volume and pattern of T1 post-contrast enhancement if available.
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Bevacizumab 10 mg/kg intravenous infusion at onset of exacerbation and, if needed, a second time during the plasma exchange phase.
Other Name: Avastin
Study Objective: The overall objective is to evaluate the tolerability/safety and efficacy of adding bevacizumab (Avastin®) to standard of care therapy in improving clinical and radiologic outcomes of acute optic neuritis and/or transverse myelitis in neuromyelitis optica and neuromyelitis optica spectrum disorders.
Primary Objective: To compare the clinical and radiographic outcome following acute optic neuritis and/or transverse myelitis in NMO/NMOSD in patients who receive 1-2 doses of 10 mg/kg dose of bevacizumab (Avastin®) in addition to standard medical therapy.
- To determine the effect of Avastin on NMO clinical scores (Expanded Disability Status Scale, Timed 25-foot Walk and Low Contrast Visual Acuity [LCVA]).
- To evaluate the safety and tolerability of a 10 mg/kg dose of intravenous Avastin.
- To determine the frequency of adverse events with Avastin in this patient population.
- To determine the effect of Avastin on MRI lesion size and extent.
The duration of the investigation is 1-2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01777412
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Michael Levy, MD, PhD||Johns Hopkins University|