Treatment of West Nile Virus With MGAWN1

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

Detailed Description
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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.

Official Title
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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

Conditions
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West Nile Neuroinvasive Disease, West Nile Virus Infection, Encephalitis, Meningitis, Acute Flaccid Paralysis, West Nile Fever

Intervention / Treatment
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* Biological: MGAWN1
* Biological: Placebo - normal saline


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MGAWN1<br>30 mg/kg single intravenous infusion of MGAWN1 | Biological: MGAWN1<br>* Humanized monoclonal to West Nile virus. Dose = 30 mg/kg actual body weight intravenous, one dose at Day 0.<br>|
| Placebo Comparator: Placebo - Normal Saline<br>single intravenous infusion of saline placebo | Biological: Placebo - normal saline<br>* Normal Saline intravenous, volume same as active comparator, one dose at Day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Study Day 2, 7, 14, 28, and 120 | 
| 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 | 120 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Study Day 2, 7, 14, 28, and 120 | 
| 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. | Study Day 0, 2, 7, 14, 28, and 120 | 
| Time to a >= 1 Point Reduction in the Modified Rankin Scale Score |  | Study Day 2, 7, 14, 28, and 120 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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WNV, WNND, West Nile virus, Encephalitis, Meningitis, Acute Flaccid Paralysis, Monoclonal Antibody, West Nile Fever, WNF