Treatment of West Nile Virus With MGAWN1

Phase 2

Terminated

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

Interventions: Biological: Placebo - normal saline
Biological: MGAWN1

Registration Number: NCT00927953

Lead Sponsor: MacroGenics

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Provide written informed consent
Be >=18 years of age at the time of enrollment
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
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
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:
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)

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo - Normal Saline	Placebo - normal saline	single intravenous infusion of saline placebo
MGAWN1	MGAWN1	30 mg/kg single intravenous infusion of MGAWN1

Primary Outcome Measures

Name	Time	Method
The Number of West Nile Neuroinvasive Disease (WNND) Participants Who Show Improvement in the Modified Rankin Scale (MRS) (>=1 Improvement in Score)	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	120 days	Includes adverse events considered possibly, probably, or definitely related to study drug

Secondary Outcome Measures

Name	Time	Method
The Number of Participants With a Favorable Neurologic Outcome	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	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	Study Day 2, 7, 14, 28, and 120