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Trial record 1 of 10 for:    "West Nile Fever"
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Treatment of West Nile Virus With MGAWN1 (PARADIGM)

This study has been terminated.
(Early termination due to the inability to enroll (13 of 120 subjects enrolled))
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT00927953
First received: June 24, 2009
Last updated: October 8, 2012
Last verified: October 2012
History of Changes
  Purpose

This study will test a drug called MGAWN1 for the treatment of West Nile infections.


Condition Intervention Phase
West Nile Neuroinvasive Disease
West Nile Virus Infection
Encephalitis
Meningitis
Acute Flaccid Paralysis
West Nile Fever
 Biological: MGAWN1
Biological: Placebo - normal saline
 Phase 2

Access to an investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by MacroGenics:

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) [ Time Frame: Study Day 2, 7, 14, 28, and 120 ] [ Designated as safety issue: No ]

    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 [ Time Frame: 120 days ] [ Designated as safety issue: No ]
    Includes adverse events considered possibly, probably, or definitely related to study drug


Secondary Outcome Measures:
  • The Number of Participants With a Favorable Neurologic Outcome [ Time Frame: Study Day 2, 7, 14, 28, and 120 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Study Day 0, 2, 7, 14, 28, and 120 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Study Day 2, 7, 14, 28, and 120 ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: May 2009
Study Completion Date: May 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MGAWN1
30 mg/kg single intravenous infusion of MGAWN1
 Biological: MGAWN1
Humanized monoclonal to West Nile virus. Dose = 30 mg/kg actual body weight intravenous, one dose at Day 0.
Placebo Comparator: Placebo - Normal Saline
single intravenous infusion of saline placebo
 Biological: Placebo - normal saline
Normal Saline intravenous, volume same as active comparator, one dose at Day 0

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00927953

Sponsors and Collaborators
MacroGenics
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Director: Anastasia Daifotis, M.D. MacroGenics
  More Information

No publications provided

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT00927953     History of Changes
Other Study ID Numbers: CP-MGAWN1-02
Study First Received: June 24, 2009
Results First Received: April 10, 2012
Last Updated: October 8, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by MacroGenics:
West Nile virus
WNV
Encephalitis
Meningitis
Acute Flaccid Paralysis
 Monoclonal Antibody
WNND
West Nile Fever
WNF

Additional relevant MeSH terms:
West Nile Fever
Central Nervous System Infections
Encephalitis
Fever
Meningitis
Virus Diseases
Paralysis
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Viral Diseases
 Brain Diseases
Body Temperature Changes
Signs and Symptoms
Encephalitis, Arbovirus
Arbovirus Infections
Encephalitis, Viral
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Neurologic Manifestations

ClinicalTrials.gov processed this record on May 21, 2013