Efficacy of Bevacizumab (Avastin) in Treatment of Acute NMO Exacerbations

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Johns Hopkins University
Sponsor:
Collaborators:
Genentech
Guthy Jackson Charitable Foundation
Information provided by (Responsible Party):
Michael Levy, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01777412
First received: January 21, 2013
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Neuromyelitis Optica
Neuromyelitis Optica Spectrum Disorder
Drug: Bevacizumab
Phase 1

Study Type: Interventional
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).

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • 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 ]

    EDSS

    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.

    LCVA

    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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 10
Study Start Date: June 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab
Bevacizumab 10 mg/kg intravenous infusion at onset of exacerbation and, if needed, a second time during the plasma exchange phase.
Drug: Bevacizumab
Other Name: Avastin

Detailed Description:

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.

Secondary Objectives:

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01777412

Contacts
Contact: Maureen Mealy, RN 410-502-8672 mmealy1@jhmi.edu
Contact: Michael Levy, MD, PhD 443-287-4412 nmo@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Maureen Mealy, RN    410-502-8672    mmealy1@jhmi.edu   
Contact: Michael Levy, MD, PhD    443-287-4412    nmo@jhmi.edu   
Principal Investigator: Michael Levy, MD, PhD         
Sponsors and Collaborators
Johns Hopkins University
Genentech
Guthy Jackson Charitable Foundation
Investigators
Principal Investigator: Michael Levy, MD, PhD Johns Hopkins University
  More Information

Additional Information:
No publications provided

Responsible Party: Michael Levy, Assistant Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01777412     History of Changes
Other Study ID Numbers: Avastin_NMO_1
Study First Received: January 21, 2013
Last Updated: May 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
NMO
NMOSD
NMO-IgG
Aquaporin-4
AQP4
anti-AQP4

Additional relevant MeSH terms:
Neuromyelitis Optica
Disease
Multiple Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Myelitis, Transverse
Optic Neuritis
Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014