This study will examine whether the experimental drug Omr-IgG-am ™ (Trademark) IV is safe and effective for treating West Nile virus (WNV) disease. Symptoms of WNV may vary from fever and headache, to a polio-like syndrome with paralysis, to coma and brain changes like those of a stroke, rarely resulting in death. Omr-IgG-am ™ (Trademark) IV contains immunoglobulin G antibodies (substances in the blood that fight infection) plus antibodies that are specific for the West Nile virus (WNV).

Hospitalized patients 18 years of age and older diagnosed with or suspected of having WNV infection may be eligible for this 3-month study. Patients will be hospitalized for several days or more until they are well enough to go home and will undergo the following tests and procedures:

- Physical examination: Patients have a brief physical exam and interview about health problems every time they are seen in the hospital, and then at clinic visits scheduled at 2 weeks, 1 month, and 3 months.

- Blood tests: Blood samples are collected during the first 7 days of the study and at each of the follow-up visits to determine if virus is still in the blood and how it is affecting the body, and to evaluate the safety of the treatment. (The first fifteen patients receiving each dose level of the study drug , 0.5 or 1.0 kg/body weight, will have blood drawn somewhat more frequently. See Treatment below.)

- Electrocardiogram (EKG) to evaluate the safety of the treatment and compare the effects of the different treatments on the heart.

- Magnetic resonance imaging (MRI): MRI scans are done within 72 hours of beginning the study and 1 month after that to look for abnormalities in the brains of patients with WNV and see if the abnormalities can predict how an individual will recover. For the scan, the patient lies on a table that is moved into the narrow tunnel-like machine with a strong magnetic field. During the procedure, a contrast agent that brightens the images is injected through a catheter placed in an arm vein.

- Neurological examination and neurological function tests: Participants are tested to see if the West Nile virus has affected their thinking and ability to perform normal daily activities. These tests will be done at the start of the study, throughout hospitalization, at days 7 and 14 from the time the patient receives the study medication, and at the 1- and 3-month follow-up visits. The tests involve answering a number of questions and performing simple tasks, such as squeezing a hand or lifting a foot.

- Treatment: Patients will be randomly assigned to receive either Omr-IgG-am ™ (Trademark) IV or one of two placebos: Polygam (a standard immunoglobulin preparation without West Nile antibodies) or saline (salt water). In all cases, the drug will be infused through a catheter (plastic tube) placed in a vein in the arm over 4 to 18 hours. (The duration of the infusion depends on the dose of the drug and the patient's weight.) The first group of patients in the Omr-IgG-am ™ (Trademark) IV and Polygam groups will receive 0.5 gram/kg body weight of the drug. If there are no serious side effects, the second group will be given 1.0 gram/kg body weight.

- Patients who develop weakness in their arms or legs have the following additional studies:

a. Electromyography (EMG) to study the electrical activity of the muscle. For this test, needles are placed into a muscle to record the electrical activity at that site.

b. Nerve conduction studies to measure how well the nerves are working. A small charge of electricity is delivered to a nerve in the affected limb, triggering a muscle to tighten or bend. Small wire electrodes are attached to the skin to measure the time is takes for the nerve to move the electrical current from one part of the limb to another.

c. Spinal MRI to see if the virus is affecting the spinal cord.

Condition	Treatment or Intervention	Phase
West Nile Virus	Drug: Omr-IgG-am	Phase II

Further Study Details: 

Expected Total Enrollment:  20

Investigators will assess whether Omr-IgG-am, ian ntravenous immunoglobulin (IVIg) containing antibodies specific for West Nile virus (WNV), is safe and well-tolerated in patients with suspected or laboratory diagnosed 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 a positive laboratory test 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™ (Trademark), Polygam® (Registered Trademark) S/D (IVIG containing no anti-WNV antibodies) or normal 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™ (Trademark) or Polygam® (Registered Trademark) S/D or a comparable volume of normal saline. The second cohort will receive 1 gram/kg of either immunoglobin preparation or normal saline. All patients will be followed for safety, natural history endpoints, and efficacy. A subset of patients will have pharmacokinetics measurements of specific anti-WNV antibodies assessed following treatment.

The primary endpoints are safety and tolerability following Omr-IgG-am™ (Trademark) 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. This combined endpoint will be measured using four standardized measures of cognitive and functional status: the Barthel Index; the Modified Rankin Scale; the Glasgow Outcome Score; and the Modified Mini-Mental Status Examination. A comparison of outcomes will be made for the group receiving Omr-IgG-am™ (Trademark) versus those receiving either placebo, and between the two placebo groups. Other secondary endpoints include the proportion of patients in each group returning to pre-morbid baseline and each subject's improvement at 3 months as compared to that subject's worst (of any previous) evaluation.

Natural history endpoints will also be assessed. They will include the duration of intensive care unit (ICU) and hospital stay, development and persistence of WNV-specific IgG and IgM antibodies, combined functional score and mortality at 3 months between the group with encephalitis and/or myelitis at baseline versus the group with a positive WNV test only, outcomes in patients treated late in coma and correlation of outcome with time-to-treatment following symptom onset

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
In order to participate in this clinical trial, all subjects (or legal representative) must provide written informed consent. Only patients meeting entry criteria will be enrolled. Eligible subjects must fall into one of two categories:
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 greater than or equal to 4 per mm(3) corrected for significant red blood cell contamination.
Ratio of CSF: plasma glucose of greater than or equal to 40% (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 described 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 greater than 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 7.5 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
known history of hypersensitivity to maltose.
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 80,000/mm(3)
Hematocrit greater than 55%
Platelet count greater than 700,000/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, cerebrovascular accident, or other infectious disease, including confirmed infections with other flaviviruses)
Pregnant or breastfeeding (negative serum or urine pregnancy test within previous 72 hours if 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 treatment of WNV or hepatitis within 15 days prior to study entry

Maryland
      Warren G. Magnuson Clinical Center (CC), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  030306; 03-CC-0306
Record last reviewed:  July 28, 2004
Last Updated:  November 23, 2004
Record first received:  September 22, 2003
ClinicalTrials.gov Identifier:  NCT00069316
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08