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Treatment of West Nile Virus With MGAWN1 (PARADIGM)

Primary Purpose

West Nile Neuroinvasive Disease, West Nile Virus Infection, Encephalitis

Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
MGAWN1
Placebo - normal saline
Sponsored by
MacroGenics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for West Nile Neuroinvasive Disease focused on measuring West Nile virus, WNV, Encephalitis, Meningitis, Acute Flaccid Paralysis, Monoclonal Antibody, WNND, West Nile Fever, WNF

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Provide written informed consent
  2. Be >=18 years of age at the time of enrollment

  3. Have West Nile Fever defined as:

    1. temperature >38°C, headache, AND
    2. positive diagnostic test for WNV Ribonucleic acid or Immunoglobulin M with serum or cerebrospinal fluid (CSF)

    OR have West Nile Neuroinvasive Disease (includes neurological signs and/or symptoms of West Nile meningitis, encephalitis, and/or acute flaccid paralysis), defined as:

    • West Nile encephalitis (must meet criteria a and b below)

    1. Encephalopathy (depressed or altered level of consciousness, lethargy, or personality change lasting 24 hours)

    2. CSF pleocytosis >=5 cells/mm^3

      AND/OR

      • West Nile meningitis (must meet criteria c and d)

    3. Clinical signs of meningeal inflammation, including nuchal rigidity, Kernig or Brudzinski sign, photophobia, or phonophobia

    4. CSF pleocytosis >=5 cells/mm^3

      AND/OR

      • Acute flaccid paralysis (must meet criteria e and f)

    5. Acute onset of limb weakness with marked progression over 48 hours

    6. Two or more of the following conditions:

      • asymmetry to weakness
      • areflexia or hyporeflexia of affected limb(s)
      • absence of pain, paresthesia, or numbness in affected limb(s)
      • CSF pleocytosis >=5 cells/mm^3
      • CSF elevated protein levels (4.5 g/L)
      • electrodiagnostic studies consistent with an anterior horn cell process
      • or abnormal increased signal in the anterior gray matter as documented by spinal cord magnetic resonance imaging

  4. Have epidemiological factors consistent with West Nile Virus infection (must meet criterion a or b below):

    1. Appropriate time of year for West Nile Virus transmission in region
    2. Travel history to a region where West Nile Virus is active
  5. Develop signs and/or symptoms within 14 days before study enrollment.

  6. If female of childbearing potential or male and in a sexual relationship with a female of childbearing potential, agree (or have partner agree) to practice abstinence or use 2 of the following methods of contraception for 120 days (approximately 4 months) after study drug administration:

    1. Oral contraceptives, or other form of hormonal birth control including hormonal vaginal rings or transdermal patches
    2. An intrauterine device
    3. Barrier contraception (condom) with a spermicide (i.e., female subject ensures use by male partner[s])
    4. Any other equivalent method of contraception (as judged by the investigator)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    MGAWN1

    Placebo - Normal Saline

    Arm Description

    30 mg/kg single intravenous infusion of MGAWN1

    single intravenous infusion of saline placebo

    Outcomes

    Primary Outcome Measures

    The Number of West Nile Neuroinvasive Disease (WNND) Participants Who Show Improvement in the Modified Rankin Scale (MRS) (>=1 Improvement in Score)
    The MRS is a 7-point disability scale that assesses the degree of disability in subjects with neurological impairment. Possible scores range from 0 (perfect health) up to 5 (severe disability). The scale is as follows: 0 = No symptoms at all 1 = No significant disability despite symptoms; 2 = Slight disability; 3 = Moderate disability; 4 = Moderately severe disability; 5 = Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6 = Dead
    The Number of Participants Who Had At Least 1 Treatment-Related Adverse Event
    Includes adverse events considered possibly, probably, or definitely related to study drug

    Secondary Outcome Measures

    The Number of Participants With a Favorable Neurologic Outcome
    Favorable neurologic outcome responders are defined as subjects whose Modified Rankin Score is <=2. The MRS is a 7-point disability scale that assesses the degree of disability in subjects with neurological impairment. Possible scores range from 0 (perfect health) up to 5 (severe disability). The scale is as follows: 0 = No symptoms at all 1 = No significant disability despite symptoms; 2 = Slight disability; 3 = Moderate disability; 4 = Moderately severe disability; 5 = Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6 = Dead.
    Mean Modified Rankin Scale Scores
    The MRS is a 7-point disability scale that assesses the degree of disability in subjects with neurological impairment. Possible scores range from 0 (perfect health) up to 5 (severe disability). The scale is as follows: 0 = No symptoms at all 1 = No significant disability despite symptoms; 2 = Slight disability; 3 = Moderate disability; 4 = Moderately severe disability; 5 = Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6 = Dead.
    Time to a >= 1 Point Reduction in the Modified Rankin Scale Score

    Full Information

    First Posted
    June 24, 2009
    Last Updated
    February 4, 2022
    Sponsor
    MacroGenics
    Collaborators
    National Institute of Allergy and Infectious Diseases (NIAID)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00927953
    Brief Title
    Treatment of West Nile Virus With MGAWN1
    Acronym
    PARADIGM
    Official Title
    Phase 2, Stratified, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety and Efficacy of MGAWN1 in Subjects With Laboratory-documented West Nile Fever or Suspected Central Nervous System Infection Due to West Nile Virus
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2022
    Overall Recruitment Status
    Terminated
    Why Stopped
    Early termination due to the inability to enroll (13 of 120 subjects enrolled)
    Study Start Date
    May 2009 (undefined)
    Primary Completion Date
    February 2011 (Actual)
    Study Completion Date
    May 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    MacroGenics
    Collaborators
    National Institute of Allergy and Infectious Diseases (NIAID)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study will test a drug called MGAWN1 for the treatment of West Nile infections.
    Detailed Description
    The objective of this study is to evaluate the safety, efficacy, and pharmacokinetics of MGAWN1 in subjects with West Nile Fever or a syndrome compatible with West Nile Neuroinvasive Disease (WNND) [encephalitis, meningitis, or acute flaccid paralysis]. Subjects can be enrolled based on a syndrome compatible with WNND, and do not need documented West Nile virus infection.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    West Nile Neuroinvasive Disease, West Nile Virus Infection, Encephalitis, Meningitis, Acute Flaccid Paralysis, West Nile Fever
    Keywords
    West Nile virus, WNV, Encephalitis, Meningitis, Acute Flaccid Paralysis, Monoclonal Antibody, WNND, West Nile Fever, WNF

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    13 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    MGAWN1
    Arm Type
    Experimental
    Arm Description
    30 mg/kg single intravenous infusion of MGAWN1
    Arm Title
    Placebo - Normal Saline
    Arm Type
    Placebo Comparator
    Arm Description
    single intravenous infusion of saline placebo
    Intervention Type
    Biological
    Intervention Name(s)
    MGAWN1
    Intervention Description
    Humanized monoclonal to West Nile virus. Dose = 30 mg/kg actual body weight intravenous, one dose at Day 0.
    Intervention Type
    Biological
    Intervention Name(s)
    Placebo - normal saline
    Intervention Description
    Normal Saline intravenous, volume same as active comparator, one dose at Day 0
    Primary Outcome Measure Information:
    Title
    The Number of West Nile Neuroinvasive Disease (WNND) Participants Who Show Improvement in the Modified Rankin Scale (MRS) (>=1 Improvement in Score)
    Description
    The MRS is a 7-point disability scale that assesses the degree of disability in subjects with neurological impairment. Possible scores range from 0 (perfect health) up to 5 (severe disability). The scale is as follows: 0 = No symptoms at all 1 = No significant disability despite symptoms; 2 = Slight disability; 3 = Moderate disability; 4 = Moderately severe disability; 5 = Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6 = Dead
    Time Frame
    Study Day 2, 7, 14, 28, and 120
    Title
    The Number of Participants Who Had At Least 1 Treatment-Related Adverse Event
    Description
    Includes adverse events considered possibly, probably, or definitely related to study drug
    Time Frame
    120 days
    Secondary Outcome Measure Information:
    Title
    The Number of Participants With a Favorable Neurologic Outcome
    Description
    Favorable neurologic outcome responders are defined as subjects whose Modified Rankin Score is <=2. The MRS is a 7-point disability scale that assesses the degree of disability in subjects with neurological impairment. Possible scores range from 0 (perfect health) up to 5 (severe disability). The scale is as follows: 0 = No symptoms at all 1 = No significant disability despite symptoms; 2 = Slight disability; 3 = Moderate disability; 4 = Moderately severe disability; 5 = Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6 = Dead.
    Time Frame
    Study Day 2, 7, 14, 28, and 120
    Title
    Mean Modified Rankin Scale Scores
    Description
    The MRS is a 7-point disability scale that assesses the degree of disability in subjects with neurological impairment. Possible scores range from 0 (perfect health) up to 5 (severe disability). The scale is as follows: 0 = No symptoms at all 1 = No significant disability despite symptoms; 2 = Slight disability; 3 = Moderate disability; 4 = Moderately severe disability; 5 = Severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6 = Dead.
    Time Frame
    Study Day 0, 2, 7, 14, 28, and 120
    Title
    Time to a >= 1 Point Reduction in the Modified Rankin Scale Score
    Time Frame
    Study Day 2, 7, 14, 28, and 120

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Provide written informed consent Be >=18 years of age at the time of enrollment Have West Nile Fever defined as: temperature >38°C, headache, AND positive diagnostic test for WNV Ribonucleic acid or Immunoglobulin M with serum or cerebrospinal fluid (CSF) OR have West Nile Neuroinvasive Disease (includes neurological signs and/or symptoms of West Nile meningitis, encephalitis, and/or acute flaccid paralysis), defined as: • West Nile encephalitis (must meet criteria a and b below) Encephalopathy (depressed or altered level of consciousness, lethargy, or personality change lasting 24 hours) CSF pleocytosis >=5 cells/mm^3 AND/OR • West Nile meningitis (must meet criteria c and d) Clinical signs of meningeal inflammation, including nuchal rigidity, Kernig or Brudzinski sign, photophobia, or phonophobia CSF pleocytosis >=5 cells/mm^3 AND/OR • Acute flaccid paralysis (must meet criteria e and f) Acute onset of limb weakness with marked progression over 48 hours Two or more of the following conditions: asymmetry to weakness areflexia or hyporeflexia of affected limb(s) absence of pain, paresthesia, or numbness in affected limb(s) CSF pleocytosis >=5 cells/mm^3 CSF elevated protein levels (4.5 g/L) electrodiagnostic studies consistent with an anterior horn cell process or abnormal increased signal in the anterior gray matter as documented by spinal cord magnetic resonance imaging Have epidemiological factors consistent with West Nile Virus infection (must meet criterion a or b below): Appropriate time of year for West Nile Virus transmission in region Travel history to a region where West Nile Virus is active Develop signs and/or symptoms within 14 days before study enrollment. If female of childbearing potential or male and in a sexual relationship with a female of childbearing potential, agree (or have partner agree) to practice abstinence or use 2 of the following methods of contraception for 120 days (approximately 4 months) after study drug administration: Oral contraceptives, or other form of hormonal birth control including hormonal vaginal rings or transdermal patches An intrauterine device Barrier contraception (condom) with a spermicide (i.e., female subject ensures use by male partner[s]) Any other equivalent method of contraception (as judged by the investigator)

    12. IPD Sharing Statement

    Learn more about this trial

    Treatment of West Nile Virus With MGAWN1

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