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

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).

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01777412
Enrollment
10
Registered
2013-01-28
Start date
2013-06-30
Completion date
2015-05-31
Last updated
2015-08-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorder

Keywords

NMO, NMOSD, NMO-IgG, Aquaporin-4, AQP4, anti-AQP4

Brief 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.

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.

Interventions

DRUGBevacizumab

Sponsors

Genentech, Inc.
CollaboratorINDUSTRY
Guthy Jackson Charitable Foundation
CollaboratorOTHER
Johns Hopkins University
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No

Inclusion 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.

Design outcomes

Primary

MeasureTime frameDescription
Baseline Expanded Disability Status Score (EDSS)Admission to hospitalEDSS 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.
Safety Assessment and Side Effects91 daysFrequency and severity of adverse events and side effects. Serious adverse events are considered those which are life threatening, lead to hospitalization and related to the drug. Side effects are considered minor effects of the experimental drug that do not significantly impact the care of the patient with the experimental drug.
Follow-Up Expanded Disability Status Score (EDSS)Follow-up visit 91 days after admissionEDSS 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.

Countries

United States

Participant flow

Participants by arm

ArmCount
Bevacizumab
Bevacizumab 10 mg/kg intravenous infusion at onset of exacerbation and, if needed, a second time during the plasma exchange phase in additional 5 days of 1000 mg methylprednisolone infusion. There was no placebo or comparator group.
10
Total10

Baseline characteristics

CharacteristicBevacizumab
Age, Continuous45.5 years
STANDARD_DEVIATION 15.5
Anti-AQP4 antibody serostatus
Negative
4 participants
Anti-AQP4 antibody serostatus
Positive
6 participants
Diagnosis
High risk for NMO
3 participants
Diagnosis
NMO/NMOSD
7 participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
1 Participants
Race (NIH/OMB)
Black or African American
2 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
White
7 Participants
Sex: Female, Male
Female
9 Participants
Sex: Female, Male
Male
1 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
1 / 10
serious
Total, serious adverse events
1 / 10

Outcome results

Primary

Baseline Expanded Disability Status Score (EDSS)

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.

Time frame: Admission to hospital

ArmMeasureValue (MEDIAN)
BevacizumabBaseline Expanded Disability Status Score (EDSS)3.5 units on a scale
Primary

Follow-Up Expanded Disability Status Score (EDSS)

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.

Time frame: Follow-up visit 91 days after admission

ArmMeasureValue (MEDIAN)
BevacizumabFollow-Up Expanded Disability Status Score (EDSS)3.0 units on a scale
Primary

Safety Assessment and Side Effects

Frequency and severity of adverse events and side effects. Serious adverse events are considered those which are life threatening, lead to hospitalization and related to the drug. Side effects are considered minor effects of the experimental drug that do not significantly impact the care of the patient with the experimental drug.

Time frame: 91 days

ArmMeasureGroupValue (NUMBER)
BevacizumabSafety Assessment and Side EffectsSerious Adverse Event: Hospitalization1 participants
BevacizumabSafety Assessment and Side EffectsSide Effects0 participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026