C1-esterase Inhibitor (Cinryze) for Acute Treatment of Neuromyelitis Optica Exacerbation
Condition: Neuromyelitis Optica
MeSH terms: Neuromyelitis Optica
Intervention: C1-esterase inhibitor (Cinryze)
Intervention MeSH terms: Complement C1s; Complement C1 Inhibitor Protein; Complement C1 Inactivator Proteins
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: 65 Years
Healthy volunteers: No
Keywords: Neuromyelitis optica; Devic's disease; NMO; Devic

Summary:

      The overall objective is to evaluate the tolerability/safety and preliminary efficacy of
      CINRYZE® (C1 esterase inhibitor [human]) as add-on therapy for treatment of acute optic
      neuritis and/or transverse myelitis in NMO and NMOSD.

      Primary Objective: To evaluate the safety and tolerability of 3-5 doses of 1000 - 2000 Units
      intravenous CINRYZE in NMO/NMOSD patients during an acute exacerbation.

      Secondary Objectives:

        -  To determine the frequency of adverse events with CINRYZE in this patient population.

        -  To determine the effect of CINRYZE on NMO clinical scores (Expanded Disability Status
           Scale and Low Contrast Visual Acuity).

        -  To compare the change in MRI lesion size and extent following a course of CINRYZE.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Able and willing to provide written informed consent.

          2. 18-65 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. Diagnosis of NMO according to the 2006 revisions of the Wingerchuk diagnostic criteria
             for NMO (Wingerchuk, 2006), 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 post-menopausal, which is defined as >2 years without menses or, in
        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 Of child-bearing 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.

        C. Subject has a negative serum pregnancy test at screening and agrees to one of the
        following:

          1. Complete abstinence from intercourse for the period from consent into the study until
             6 months after the last dose of investigational product; or,

          2. 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:

        i. Oral contraceptives (either combined or progesterone only) ii. Injectable progesterone
        iii. Levonorgestrel implants iv. Estrogenic vaginal ring v. Percutaneous contraceptive
        patches vi. Intrauterine device (IUD) or intrauterine system (IUS) with a documented
        failurerate of <1% per year vii. 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 viii. Double barrier method: condom and an occlusive cap
        (diaphragm or cervical/vault caps) with a vaginal spermicidal agent
        (foam/gel/film/cream/suppository).

        Exclusion Criteria:

          1. Current evidence or known 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. Previous serious opportunistic or atypical infections.

               3. History of positive serology for hepatitis B.

               4. Prior history, or suspicion, of tuberculosis (TB)

               5. History of positive serology for HIV.

          2. History of clinically significant CNS trauma (e.g. traumatic brain injury, cerebral
             contusion, spinal cord compression).

          3. History or presence of myelopathy due to spinal cord compression by disc or vertebral
             disease.

          4. Past or current history of medically significant adverse effects (including allergic
             reactions) from:

             a. Corticosteroids

          5. 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.

          6. 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, as determined by the PI of the study.

          7. 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.

          8. Current participation in any other interventional clinical trial. Participation in
             non-interventional trial requires approval of the protocol by investigator.