Treatment of West Nile Virus With MGAWN1

Meningitis Clinical Trial

— PARADIGM  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00927953
• Other study ID #: CP-MGAWN1-02
• Status: Terminated
• Phase: Phase 2
• Start date: May 2009
• Est. completion date: May 2011

Study information

• Verified date: January 2022
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: May 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acute Flaccid Paralysis
• Encephalitis
• Fever
• Infections
• Meningitis
• Paralysis
• West Nile Fever
• West Nile Neuroinvasive Disease
• West Nile Virus Infection

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
MacroGenics	National Institute of Allergy and Infectious Diseases (NIAID)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	Time to a >= 1 Point Reduction in the Modified Rankin Scale Score		Study Day 2, 7, 14, 28, and 120