Primary:

• To assess and characterize the safety and tolerability of Omr-IgG-am in a population of hospitalized patients with laboratory diagnosed or suspected WNV disease.

Secondary:

• To assess pharmacokinetics of specific anti-West Nile antibodies following intravenous administration of Omr-IgG-am.
• To estimate efficacy of Omr-IgG-am in reducing morbidity and mortality for patients with known or suspected WNV infection who receive WNV specific IVIg versus similar patients who receive either standard IVIg or normal saline.
• To further characterize the natural history of severe WNV infection.

Condition	Treatment or Intervention	Phase
West Nile Fever	Vaccine: Omr-IgG-am (TM)	Phase I Phase II

Investigators will assess whether Omr-IgG-am, intravenous immunoglobulin (IVIg) containing antibodies specific for West Nile virus (WNV), is safe and well-tolerated in patients with suspected or confirmed WNV disease. An initial estimation of efficacy will also be made.

This Phase I/II study will enroll hospitalized adults with a presumptive diagnosis of West Nile encephalitis and/or myelitis or those with confirmed diagnosis of WNV infection who are at high risk for progressing to severe neurologic disease based on age or immunosuppression. Patients will be randomized in blocks of five to receive either Omr-IgG-am, Polygam S/D (IVIG containing no anti-WNV antibodies) or saline placebo in a ratio of 3:1:1. Patients and investigators will be blinded to treatment assignments.

Patients will receive a single intravenous dose of active treatment or one of two placebos. Two dosing cohorts will be accrued sequentially. The first cohort will receive 0.5 grams/kg of Omr-IgG-am or Polygam S/D or a comparable volume of saline. The second cohort will receive 1 gram/kg of either preparation or saline. All patients will be followed for safety, natural history and efficacy. A subset of patients will have pharmacokinetics of specific anti-WNV antibodies assessed following treatment.

The primary endpoints are safety and tolerability following Omr-IgG-am administration. Secondary endpoints include pharmacokinetics of specific anti-WNV antibodies, mortality in confirmed WNV positive patients, and the combination of mortality and functional status at three months in both confirmed WNV-infected patients and all patients by intention to treat.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:

• A. Hospitalized patients greater than or equal to 18 years of age with encephalitis and/or myelitis as defined below. New neurologic abnormality: Asymmetric extremity weakness without sensory abnormality; or Other neurologic abnormality (including altered level of consciousness, dysarthria and dysphagia) plus fever (subjective or objective) within the previous 4 days AND CSF examination within the previous 72 hours showing: Absence of organism on gram or fungal stain; White blood cell count; 4 per (mm)3 corrected for significant red blood cell contamination. Ratio of CSF: plasma glucose of 40 percent (CSF glucose / plasma glucose greater than or equal to 0.4) OR
• B. Hospitalized patients without encephalitis and /or myelitis as defined below who meet the following criteria: A positive IgM serology or PCR test for WNV in blood or cerebrospinal fluid AND Clinical illness compatible with WNV infection as defined by occurrence of greater than or equal to 3 of the following findings during the preceding less than or equal to 7 days: Diarrhea, Headache, Fever, 38 degrees Celsius, Nausea and/or vomiting, Myalgias and/or arthralgias, Nuchal rigidity, Macular or papular rash, New neurological abnormality (not suggestive of encephalitis or myelitis)

AND A risk factor for the development of WNV neurologic disease as defined by: Age greater than or equal to 40 years, or Age greater than or equal to 18 years plus immunosuppression, as defined by any of the following: Hematologic malignancy; Previous diagnosis of diabetes mellitus; Chemotherapy within previous 4 weeks; Stem cell transplant recipient or solid organ transplant recipient; Taking immunosuppressive medications; including prednisone greater than or equal to .5 mg/day within the previous 4 weeks; History of human immunodeficiency virus (HIV) infection; Congenital immunodeficiency syndrome (including common variable immunodeficiency)

EXCLUSION CRITERIA:

• Unable to obtain valid informed consent.
• History of intolerance (including anaphylaxis) to IVIg or related compounds.
• Known history of IgA deficiency.
• History of (or at time of study entry) hyperviscosity syndrome including but not limited to: Waldenstrom's macroglobulinemia, multiple myeloma, total white blood cell count greater than 80000/mm(3), Hematocrit greater than 55 percent, platelet count greater than 700000/mm(3).
• Meets criteria of Class III or IV of the New York Heart Association Classification for congestive heart failure patients.
• Serum creatinine greater than 2.5 mg/dL or requires dialysis.
• Alternate explanation (as determined by the investigator) for clinical findings (such as structural brain lesion, cardiovascular accident, or other infectious disease including another flavivirus).
• Pregnant or breastfeeding (negative serum or urine pregnancy test required within the previous 72 hours if the woman is not postmenopausal or has not been surgically sterilized).
• Investigator's opinion that patient would be unable to adhere to protocol requirements.
• Receipt of ribavirin, interferon alpha or any investigational drug for the treatment of WNV or hepatitis within 15 days prior to study entry.
• Known history of hypersensitivity to maltose

Walla Dempsey      301 496 7453    wdempsey@niaid.nih.gov

Alabama
      University of Alabama at Birmingham (CASG), Birmingham,  Alabama,  35294,  United States; Recruiting
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      University of Southern California - Los Angeles CA, Los Angeles,  California,  90033,  United States; Recruiting
      City of Hope National Medical Center, Duarte,  California,  91010,  United States; Recruiting
      Kaiser Permanente Harbor City California, Harbor City,  California,  90710,  United States; Recruiting
      University of California, Sacramento,  California,  95817,  United States; Recruiting
Colorado
      Kaiser Permanente Colorado, Denver,  Colorado,  80205,  United States; Recruiting
      University of Colorado - Denver CO, Denver,  Colorado,  80262,  United States; Recruiting
District of Columbia
      George Washington University - Washington DC, Washington,  District of Columbia,  20037,  United States; Recruiting
Illinois
      Rush-Presbyterian-St. Luke's Medical Center, Chicago,  Illinois,  60612,  United States; Recruiting
      Loyola University Medical Center, Chicago,  Illinois,  60626,  United States; Recruiting
Indiana
      Indiana University-Purdue University At Indianapolis, Indianapolis,  Indiana,  46202-512,  United States; Recruiting
Kansas
      Via Christi Regional Medical Center, Wichita,  Kansas,  67214,  United States; Recruiting
      University of Kansas, Kansas City,  Kansas,  66160,  United States; Recruiting
Kentucky
      University of Kentucky, Lexington,  Kentucky,  40506,  United States; Recruiting
Louisiana
      Tulane University Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Louisiana State University Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
Maryland
      Johns Hopkins University, Baltimore,  Maryland,  21287,  United States; Recruiting
      National Institutes of Health, Bethesda,  Maryland,  20892,  United States; Recruiting
Michigan
      University of Michigan - Ann Arbor MI, Ann Arbor,  Michigan,  48105,  United States; Recruiting
      Wayne State University, Detroit,  Michigan,  48201,  United States; Recruiting
      William Beaumont Hospital, Royal Oak,  Michigan,  48073,  United States; Recruiting
Missouri
      St. Louis University, St. Louis,  Missouri,  63110,  United States; Recruiting
Montana
      St. James Community Hospital, Butte,  Montana,  58791,  United States; Recruiting
      Western Montana Clinic, Missoula,  Montana,  59802,  United States; Recruiting
Nebraska
      Internal Medicine Associates, North Platte,  Nebraska,  69101,  United States; Recruiting
      Nebraska Medical Center, Omaha,  Nebraska,  68198-5400,  United States; Recruiting
      McCook Clinic PC, McCook,  Nebraska,  69001,  United States; Recruiting
      Creighton University Medical Center, Omaha,  Nebraska,  68178,  United States; Recruiting
New Mexico
      University of New Mexico Albuquerque, Albuquerque,  New Mexico,  87131,  United States; Recruiting
New York
      Flushing Hospital Medical Center, Flushing,  New York,  11355,  United States; Recruiting
North Dakota
      St. Alexius Medical Center, Bismarck,  North Dakota,  58501,  United States; Recruiting
Ohio
      University Hospitals of Cleveland, Cleveland,  Ohio,  44106,  United States; Recruiting
      University of Cincinnati, Cincinnati,  Ohio,  45267-0525,  United States; Recruiting
Pennsylvania
      The Reading Hospital and Medical Center, Reading,  Pennsylvania,  55,  United States; Recruiting
      Lehigh Valley Hospital and Health Network, Allentown,  Pennsylvania,  18103,  United States; Recruiting
South Dakota
      Infectious Disease Specialists PC, Sioux Falls,  South Dakota,  57105,  United States; Recruiting
      Trinity Health Center (Town and Country), Minot,  South Dakota,  58701,  United States; Recruiting
Texas
      Wilford Hall Medical Center - Lackland AFB - TX, Lackland AFB,  Texas,  78236,  United States; Recruiting
      University of Texas Health Science Ctr - Tyler TX, Tyler,  Texas,  555,  United States; Recruiting
      University of Texas Medical Br Galveston, Galveston,  Texas,  77555-04,  United States; Recruiting
      University of Texas Health Science Ctr - San Antonio, San Antonio,  Texas,  78229,  United States; Recruiting
      University of Texas - Houston, Houston,  Texas,  77030,  United States; Recruiting
Virginia
      University of Virginia Health System, Charlottesville,  Virginia,  22908,  United States; Recruiting

Study ID Numbers:  03-107
Record last reviewed:  March 2004
Record first received:  September 4, 2003
ClinicalTrials.gov Identifier:  NCT00068055
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-29