Treatment of West Nile Virus With MGAWN1 - Full Text View

Sponsor:	MacroGenics
Collaborator:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	MacroGenics
ClinicalTrials.gov Identifier:	NCT00927953

Purpose

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

Condition	Intervention	Phase
West Nile Neuroinvasive Disease West Nile Virus Infection Encephalitis Meningitis Acute Flaccid Paralysis West Nile Fever	Biological: MGAWN1 Biological: Placebo - normal saline	Phase II

Access to an investigational treatment associated with this study is no longer available outside the clinical trial. More info ...

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Encephalitis Fever Meningitis Paralysis West Nile Virus

U.S. FDA Resources

Further study details as provided by MacroGenics:

Primary Outcome Measures:

The percentage of WNND subjects who show improvement in the modified Rankin Scale (MRS) (≥1 improvement in score) [ Time Frame: 14 Days ] [ Designated as safety issue: No ]
The percentage of WNF subjects who show ≥20% improvement from baseline in overall SF-12 score [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Evaluate the safety and tolerability of MGAWN1 in all subjects as assessed by: Incidence and severity of AEs and SAEs, Laboratory abnormalities, Vital signs, Electrocardiogram (ECG) abnormalities, Physical examination abnormalities [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Percentage of subjects with a favorable neurologic outcome [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Mean MRS scores [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Mean percent improvement from baseline score in the acute short form 12-item (SF-12) health status questionnaire score [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Mean percent improvement compared to baseline score in the Beck Depression Index derived from the SF-12 [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Medical Expenditure Prediction derived from the SF-12 [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Incidence and duration of clinical symptoms [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Time to resolution of all symptoms [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Time to resolution of fever [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Duration of hospitalization [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Disposition (home, rehabilitation, chronic nursing facility) following the initial hospitalization [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
In-hospital, and 28-day and 120-day all-cause mortality [ Time Frame: 120 Days ] [ Designated as safety issue: No ]
Duration of hospitalization [ Time Frame: 120 Days ] [ Designated as safety issue: No ]
Number of admissions to an intensive care unit [ Time Frame: 120 Days ] [ Designated as safety issue: No ]
Disposition (home, rehabilitation, chronic nursing facility) following the initial hospitalization [ Time Frame: 120 Days ] [ Designated as safety issue: No ]
Percentage of subjects who show improvement compared to baseline in the MRS and time to MRS improvement [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Time to a favorable neurologic outcome [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Mean percentage and absolute improvement compared to baseline score in Glasgow Coma Scale [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Mean percentage and absolute improvement compared to baseline score in Fatigue Severity Scale [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Mean percentage and absolute improvement compared to baseline score in the scored neurologic examination [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Use of mechanical ventilation at any time [ Time Frame: 120 days ] [ Designated as safety issue: No ]

Enrollment:	13
Study Start Date:	May 2010
Study Completion Date:	May 2011
Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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	Biological: Placebo - normal saline Normal Saline intravenous, volume same as active comparator, one dose at Day 0

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 RNA or IgM with serum or 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)
1. Encephalopathy (depressed or altered level of consciousness, lethargy, or personality change lasting 24 hours)
2. CSF pleocytosis ≥5 cells/mm3
  
  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/mm3
  
  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/mm3
  - 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):
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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00927953

Sponsors and Collaborators

MacroGenics

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Director:

Anastasia Daifotis, M.D.

MacroGenics

More Information

No publications provided

Responsible Party:	Anastasia Daifotis M.D. , Senior Vice President of Clinical Development, MacroGenics, Inc
ClinicalTrials.gov Identifier:	NCT00927953 History of Changes
Other Study ID Numbers:	CP-MGAWN1-02
Study First Received:	June 24, 2009
Last Updated:	July 13, 2011
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board; Canada: Health Canada; Canada: Ethics Review Committee

Keywords provided by MacroGenics:

West Nile virus
WNV
Encephalitis
Meningitis
Acute Flaccid Paralysis

Monoclonal Antibody
WNND
West Nile Fever
WNF

Additional relevant MeSH terms:

Central Nervous System Infections
Encephalitis
Fever
Meningitis
Virus Diseases
West Nile Fever
Paralysis
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Viral Diseases

Brain Diseases
Body Temperature Changes
Signs and Symptoms
Encephalitis, Arbovirus
Arbovirus Infections
Encephalitis, Viral
RNA Virus Infections
Flavivirus Infections
Flaviviridae Infections
Neurologic Manifestations

ClinicalTrials.gov processed this record on February 02, 2012