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 of the brain and spinal cord.

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

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of MGAWN1 in Subjects With Suspected Central Nervous System Infection Due to West Nile Virus

Resource links provided by NLM:

MedlinePlus related topics: Encephalitis Meningitis Paralysis

U.S. FDA Resources

Further study details as provided by MacroGenics:

Primary Outcome Measures:

The percentage of subjects treated with MGAWN1 who show improvement in the modified Rankin Scale (MRS) (≥1 improvement in score) [ Time Frame: 14 Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percentage of subjects who show improvement (≥1 improvement in score) 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 ]
Mean MRS scores [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Percent improvement from baseline in the acute SF-12 health status questionnaire score [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Percent improvement compared to baseline 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 ]
Percentage and absolute improvement compared to baseline in Glasgow Coma Score (GCS) [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Percentage of subjects with a favorable neurologic outcome (MRS 0−2) and time to a favorable outcome [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Percentage and absolute improvement compared to baseline in Fatigue Severity Scale (FSS) [ Time Frame: Pre-specified Study Days up to and including 120 Days ] [ Designated as safety issue: No ]
Percentage and absolute improvement compared to baseline in the scored neurologic examination [ 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 ]
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 ]
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 ]
Develop a PK model of MGAWN1 in the patient population [ Time Frame: 120 Days ] [ Designated as safety issue: No ]
Assess the immunogenicity of MGAWN1 as determined by antibody levels to MGAWN1 [ Time Frame: 120 Days ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	July 2009
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
MGAWN1: Experimental	Biological: MGAWN1 Humanized monoclonal to West Nile virus. Dose = 30 mg/kg actual body weight intravenous, one dose at Day 0.
Placebo - Normal Saline: Placebo Comparator	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 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 neurological signs and 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/mm^3 (≥0.005 × 10^9 cells/L)
  
  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 (≥0.005 × 10^9 cells/L)
  
  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 (≥0.005 × 10^9 cells/L)
  - 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 WNV infection (must meet criterion a or b):
1. Appropriate time of year for WNV transmission in region
2. Travel history to a region where WNV is active
Develop neurological signs and symptoms within 4 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 either abstinence or to 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 investigative team).

Exclusion Criteria:

Have clinical signs of advanced CNS dysfunction, as assessed by GCS of 3−5
Have received ribavirin or interferon alpha within 15 days before study enrollment or plan to receive during the study period
Have an underlying medical condition that could cause symptoms of encephalitis, meningitis, or acute flaccid paralysis as judged by the investigator
Have gastrointestinal or respiratory symptoms that are not consistent with WNV infections as judged by the investigator
Have a history of severe allergic reaction to humanized monoclonal antibodies
Have other laboratory parameters suggestive of a non-viral cause of the subject's medical condition, including but not limited to:
1. CSF (if performed) gram stain positive for organisms
2. CSF (if performed) glucose <70 mg/dL
Are pregnant or breastfeeding. Females of childbearing potential must have a negative urine pregnancy test within 4 days before study enrollment.
Have received any investigational drug within 30 days
Have any condition that in the investigator's opinion would increase the risk to the subject while undergoing treatment with MGAWN1 or otherwise warrant exclusion from the study

Contacts and Locations

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

Contacts

Contact: Lara Blake

301-354-3819

wnv@macrogenics.com

Locations

United States, Arizona
Chandler Regional Medical Center	Recruiting
Chandler, Arizona, United States, 85224
Principal Investigator: Brian Tiffany, M.D.
Mercy Gilbert Medical Center	Recruiting
Gilbert, Arizona, United States, 85297
Principal Investigator: Brian Tiffany, M.D.
United States, California
Grossmont Hospital	Recruiting
La Mesa, California, United States, 91942
Principal Investigator: Mohamed Bidair, M.D.
University of California, Irvine Medical Center	Recruiting
Orange, California, United States, 92868
Principal Investigator: Steven T Park, M.D.
Northridge Hospital Medical Center	Recruiting
Northridge, California, United States, 91328
Principal Investigator: Dolly Roy, M.D.
Memorial Medical Center	Recruiting
Modesto, California, United States, 95355
Principal Investigator: Salah Bibi, M.D.
United States, Colorado
Exempla St. Joseph Hospital	Recruiting
Denver, Colorado, United States, 80205
Principal Investigator: Miguel Mogyoros, M.D.
United States, Idaho
Bingham Memorial Hospital	Recruiting
Blackfoot, Idaho, United States, 83221
Principal Investigator: Thomas Faber, M.D.
Eastern Idaho Regional Medical Center	Recruiting
Idaho Falls, Idaho, United States, 83404
Contact: Kimberly Fielding 208-535-8404
Principal Investigator: Richard Nathan, D.O.
United States, North Dakota
MeritCare Health System	Recruiting
Fargo, North Dakota, United States, 58122
Principal Investigator: Paul Carson, M.D.
United States, Texas
Texas Tech University Health Sciences Center	Recruiting
El Paso, Texas, United States, 79905
Principal Investigator: Armando D Meza, M.D.
Canada, Manitoba
University of Manitoba	Recruiting
Winnipeg, Manitoba, Canada, R3A 1R9
Principal Investigator: Alan C Jackson, M.D.
Canada, Saskatchewan
Royal University Hospital, University of Saskatchewan	Recruiting
Saskatoon, Saskatchewan, Canada, S7N 0W8
Principal Investigator: Stephen E. Sanche, M.D.

Sponsors and Collaborators

MacroGenics

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Director:

John Beigel, M.D.

MacroGenics

More Information

No publications provided

Responsible Party:	MacroGenics, Inc ( John Beigel, M.D. , Director of Clinical Research )
Study ID Numbers:	CP-MGAWN1-02
Study First Received:	June 24, 2009
Last Updated:	September 21, 2009
ClinicalTrials.gov Identifier:	NCT00927953 History of Changes
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

Additional relevant MeSH terms:

Communicable Diseases
Nervous System Diseases
Central Nervous System Diseases
Central Nervous System Viral Diseases
Infection
Brain Diseases
Encephalitis

Meningitis
Virus Diseases
Paralysis
Signs and Symptoms
Central Nervous System Infections
Neurologic Manifestations

ClinicalTrials.gov processed this record on February 08, 2010