Treatment of West Nile Virus With MGAWN1 (PARADIGM)

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

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

Study Overview

• Status: Terminated
• Conditions: Encephalitis; Meningitis; West Nile Virus Infection; West Nile Fever; West Nile Neuroinvasive Disease; Acute Flaccid Paralysis
• Intervention / Treatment: Biological: MGAWN1; Biological: Placebo - normal saline

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MacroGenics
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: June 24, 2009
• First Submitted That Met QC Criteria: June 24, 2009
• First Posted (Estimate): June 25, 2009

Study Record Updates

• Last Update Posted (Actual): February 10, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Meningitis; Monoclonal Antibody; Encephalitis; West Nile virus; WNV; Acute Flaccid Paralysis; WNND; West Nile Fever; WNF
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Neurologic Manifestations; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Encephalitis; Infections; Paralysis; Fever; Meningitis; West Nile Fever
• Other Study ID Numbers: CP-MGAWN1-02