Treatment of West Nile Virus With MGAWN1

Overview

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

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: February 2011

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.

Interventions

  • Biological: MGAWN1
    • Humanized monoclonal to West Nile virus. Dose = 30 mg/kg actual body weight intravenous, one dose at Day 0.
  • Biological: Placebo – normal saline
    • Normal Saline intravenous, volume same as active comparator, one dose at Day 0

Arms, Groups and Cohorts

  • Experimental: MGAWN1
    • 30 mg/kg single intravenous infusion of MGAWN1
  • Placebo Comparator: Placebo – Normal Saline
    • single intravenous infusion of saline placebo

Clinical Trial Outcome Measures

Primary 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
    • 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
    • Includes adverse events considered possibly, probably, or definitely related to study drug

Secondary Measures

  • The Number of Participants With a Favorable Neurologic Outcome
    • Time Frame: Study Day 2, 7, 14, 28, and 120
    • 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
    • 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

Participating in This Clinical Trial

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)
  • Gender Eligibility: All

    Minimum Age: 18 Years

    Maximum Age: N/A

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • MacroGenics
    • Collaborator
      • National Institute of Allergy and Infectious Diseases (NIAID)
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • Anastasia Daifotis, M.D., Study Director, MacroGenics

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