Treatment of West Nile Virus With MGAWN1 (PARADIGM)

MacroGenics

Status and phase: Terminated; Phase 2

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

Treatments: Biological: Placebo - normal saline; Biological: MGAWN1

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00927953

CP-MGAWN1-02

Details and patient eligibility

About

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

Full 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.

Enrollment: 13 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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13 participants in 2 patient groups, including a placebo group

MGAWN1

Experimental group

Description:

30 mg/kg single intravenous infusion of MGAWN1

Treatment:

Biological: MGAWN1

Placebo - Normal Saline

Placebo Comparator group

Description:

single intravenous infusion of saline placebo

Treatment:

Biological: Placebo - normal saline