Efficacy of Bevacizumab (Avastin) in Treatment of Acute NMO Exacerbations
Condition: Neuromyelitis Optica; Neuromyelitis Optica Spectrum Disorder
MeSH terms: Neuromyelitis Optica
Intervention: Bevacizumab
Intervention MeSH terms: Bevacizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: NMO; NMOSD; NMO-IgG; Aquaporin-4; AQP4; anti-AQP4

Summary:

      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.
    

Eligibility criteria:

        Subjects eligible for enrollment must meet all of the following criteria:

          1. Able and willing to provide written informed consent.

          2. 18-70 years of age.

          3. New acute optic neuritis and/or transverse myelitis. A clinical event is defined as an
             episode of inflammation in the spinal cord and/or optic nerve leading to neurologic
             symptoms not ascribed to another disease process.

          4. Known or suspected diagnosis of NMO according to the 2006 revisions of the Wingerchuk
             diagnostic criteria for NMO or AQP4 positive NMOSD per the EFNS Guidelines. For NMO,
             subjects must have two absolute criteria:

               1. optic neuritis

               2. myelitis and at least two of three supportive criteria:

               3. presence of a contiguous spinal cord MRI lesion extending over three or more
                  vertebral segments,

               4. MRI criteria NOT satisfying the revised McDonald diagnostic criteria for MS
                  [Polman, 2011]

               5. NMO-IgG (AQP4) in serum. For NMOSD, subjects must have longitudinally extensive
                  transverse myelitis (LETM) recurrent isolated optic neuritis (RION)/bilateral
                  optic neuritis (BON), or opticospinal multiple sclerosis (OSMS) that is AQP4
                  antibody positive

          5. A female subject is eligible to enter the study if she is:

        A. Not pregnant or nursing; B. Of non-childbearing potential (i.e. women who have had a
        hysterectomy, are postmenopausal, which is defined as >2 years without menses (female
        subjects who have been post-menopausal for <2 years must be confirmed with Follicle
        Stimulating Hormone (FSH) and estradiol levels), have both ovaries surgically removed or
        have current documented tubal ligation); or,

        C. Of childbearing potential (i.e. women with functional ovaries and no documented
        impairment of oviductal or uterine function that would cause sterility). This category
        includes women with oligomenorrhoea (even severe), women who are perimenopausal or have
        just begun to menstruate. The subject must have a negative serum pregnancy test at
        screening and agrees to one of the following:

        i. Complete abstinence from intercourse for the period from consent into the study until 6
        months after the last dose of investigational product; or, ii. Consistent and correct use
        of one of the following acceptable methods of birth control for the period from consent
        into the study until 6 months after the last dose of investigational product:

          1. Oral contraceptives (either combined or progesterone only)

          2. Injectable progesterone

          3. Levonorgestrel implants

          4. Estrogenic vaginal ring

          5. Percutaneous contraceptive patches

          6. Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate
             of <1% per year

          7. Male partner sterilization (vasectomy with documentation of azoospermia) prior to the
             female subject's entry into the study; this male must be the sole partner for the
             subject

          8. Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps)
             with a vaginal spermicidal agent (foam/gel/film/cream/suppository).

        Subjects meeting any of the following criteria are not eligible and cannot enroll in the
        study:

          1. Evidence or history of clinically significant infection including:

               1. Chronic or ongoing active infectious disease requiring long term systemic
                  treatment such as, but not limited to: PML, chronic renal infection, chronic
                  chest infection with bronchiectasis, tuberculosis, or active hepatitis C.

               2. Positive test for HBsAg.

               3. Prior history, or suspicion, of tuberculosis (TB)

               4. History of positive serology for HIV.

          2. Past or current malignancy, except for

               1. Cervical carcinoma Stage 1B or less

               2. Non-invasive basal cell and squamous cell skin carcinoma

               3. Cancer diagnoses with a duration of complete response (remission) >5 years

               4. A history of hematologic malignancy excludes a subject from participation,
                  regardless of response.

          3. Recent major surgery within the last 28 days.

          4. Significant concurrent, uncontrolled medical condition including, but not limited to,
             cardiac, renal, hepatic, hematological, gastrointestinal, endocrine, immunodeficiency
             syndrome, pulmonary, cerebral, psychiatric, or neurological disease which could affect
             the subject's safety, impair the subject's reliable participation in the trial, impair
             the evaluation of endpoints, or necessitate the use of medication not allowed by the
             protocol.

          5. Use of an investigational drug or other experimental therapy for a condition other
             than NMO within 4 weeks, 5 pharmacokinetic half lives or duration of biological effect
             (whichever is longer) prior to screening.

          6. Current participation in any other interventional clinical trial. Participation in
             non-interventional trial requires approval of the protocol by investigator.