IVIG - West Nile Encephalitis: Safety and Efficacy
- Conditions
- West Nile Virus
- Interventions
- Drug: Polygam® S/DDrug: Omr-lgG-amDrug: Placebo
- Registration Number
- NCT00068055
- Brief Summary
This study will look at the safety and effectiveness of an experimental medication containing antibodies (Omr-IgG-am™) in people with West Nile Virus (WNV) who already have brain and/or spinal cord inflammation or who are at high risk of developing these problems because they have weak immune systems. WNV can cause problems such as headaches, fever, muscle weakness, coma, and death. Study investigators believe people who are not able to fight infection well may be at risk for developing neurologic problems (having to do with the brain, spinal cord, nerves, and muscles) if they get WNV infection. Up to 110 subjects, 18 years or older, will participate for about 3 months and will receive either Omr-IgG-am™, Polygam® S/D, or placebo given through a small tube placed in a blood vessel in the arm. Hospitalization, up to 5 additional study visits, blood sample collection, MRI pictures of the brain and spinal cord, and neurological, muscle, and heart activity tests are also required.
- Detailed Description
The purpose of this study is to assess whether Omr-IgG-am™, an intravenous 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 for 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-IgGam ™, Polygam® S/D (IVIG containing minimal anti-WNV antibodies) or normal saline in a ratio of 3:1:1. Patients and investigators will be blinded to treatment assignments. Patients will receive a single intravenous dose of study medication or one of two placebos. The study participants will receive 0.5 grams/kg of Omr-IgG-am™ or Polygam® S/D or a comparable volume of normal saline. All patients will be followed for safety, natural history endpoints, and efficacy. A subset of patients will have pharmacokinetic measurements 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. 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™ 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 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 62
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 96 hours showing:
- Absence of organism on gram or fungal stain
- White blood cell count greater than or equal to 4 per cubic mm 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) Serum and CSF glucose levels should be obtained within 8 hours of each other for this calculation.
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 10 days:
- Diarrhea
- Headache
- Fever > 38º C
- Nausea and/or vomiting
- Myalgias and/or arthralgias
- Nuchal rigidity
- Macular or papular rash
- New neurological abnormality 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)
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, such as but not limited to:
- Waldenstrom's macroglobulinemia
- Multiple myeloma
- Total white blood cell count > 80,000/cubic mm
- Hematocrit > 55%
- Platelet count > 700,000/cubic mm Meets criteria of Class III or IV of the New York Heart Association Classification for congestive heart failure patients Serum creatinine > 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, intravenous immunoglobulin, or any investigational drug for treatment of WNV or hepatitis within 15 days prior to study entry
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 Polygam® S/D 20 subjects to receive Polygam® S/D (IVIG). 1 Omr-lgG-am 60 subjects to receive Omr-IgG-am. 3 Placebo 20 subjects to receive normal saline.
- Primary Outcome Measures
Name Time Method Safety (including all causes of mortality) in the test IVIg (Omr-IgG-am™) group versus the 2 placebo groups, as defined by the total number of serious adverse events regardless of relatedness to study drug administration. Duration of study.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics of specific anti-WNV antibodies as measured by ELISA and PRNT methods. Baseline (pre-dose) blood sample collected immediately prior to the beginning of the infusion. After the infusion, additional blood samples collected at 1 hr, 6 hr, 12 hr, 24 hr, 72 hr, and then at Day 5, Day 7, Day 14, Day 30, Day 60 and Day 90. Mortality alone among confirmed WNV patients. At 3 months. Combined primary endpoint of mortality and morbidity among confirmed WNV patients as assessed by four scoring systems: the Barthel Index, the MRS, the GOS and the 3MS, in the experimental treatment group versus the control group. At 3 months. Proportion of patients returning to pre-morbid baseline at 3 months, between treated and untreated groups of patients with WNV infection, as assessed by two scoring systems the Barthel Index and the MRS. At 3 months. Improvement as compared to subject's own worst (of any earlier) evaluation, for each subject as defined by the combined results of the 4 neurological functional tests. At 3 months. Combined morbidity and mortality in treatment versus placebo groups for all (including those without WNV infection) subjects by intention to treat analysis. At 3 months.
Trial Locations
- Locations (69)
Idaho Falls Infectious Diseases, PLLC
🇺🇸Idaho Falls, Idaho, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
The University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
The University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Dakota Clinic at Innovis
🇺🇸Fargo, North Dakota, United States
St. Alexius Medical Center
🇺🇸Bismarck, North Dakota, United States
MeritCare Hospital
🇺🇸Fargo, North Dakota, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
University Hospital
🇺🇸Cincinnati, Ohio, United States
The University of Texas Health Science Center
🇺🇸San Antonio, Texas, United States
Wilford Hall Medical Center
🇺🇸San Antonio, Texas, United States
University of South Alabama Medical Center
🇺🇸Mobile, Alabama, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Kaiser Permanente South Bay Medical Center
🇺🇸Harbor City, California, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
University of Southern California
🇺🇸Los Angeles, California, United States
University of Arkansas
🇺🇸Little Rock, Arkansas, United States
Santa Rosa Kaiser Medical
🇺🇸Santa Rosa, California, United States
Enloe Medical Center
🇺🇸Chico, California, United States
University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Loyola University
🇺🇸Maywood, Illinois, United States
University of California Irvine
🇺🇸Orange, California, United States
Clara Maass Medical Center
🇺🇸Belleville, New Jersey, United States
Flushing Hospital Medical Center
🇺🇸Flushing, New York, United States
George Washington University Medical Center
🇺🇸Washington, District of Columbia, United States
Saint Louis University
🇺🇸St. Louis, Missouri, United States
Trinity Health - Hospital
🇺🇸Minot, North Dakota, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
The Reading Hospital and Medical Center
🇺🇸West Reading, Pennsylvania, United States
Memorial Hospital of RI
🇺🇸Pawtucket, Rhode Island, United States
Infectious Disease Consultations - Rapid City
🇺🇸Rapid City, South Dakota, United States
University of Calgary
🇨🇦Calgary, Alberta, Canada
University of Manitoba
🇨🇦Winnipeg, Manitoba, Canada
University of Toledo
🇺🇸Toledo, Ohio, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
University of Colorado
🇺🇸Denver, Colorado, United States
National Institutes of Health
🇺🇸Bethesda, Maryland, United States
VA Medical Center - Omaha
🇺🇸Omaha, Nebraska, United States
Creighton University
🇺🇸Omaha, Nebraska, United States
Exempla St. Joseph Hospital
🇺🇸Denver, Colorado, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Legacy Good Samaritan
🇺🇸Portland, Oregon, United States
The University of Texas Health Science Center at Tyler
🇺🇸Tyler, Texas, United States
Seton Medical Center
🇺🇸Daly City, California, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
Central Nebraska Medical Clinic
🇺🇸Broken Bow, Nebraska, United States
McCook Clinic, PC
🇺🇸McCook, Nebraska, United States
Great Plains Regional Medical Center
🇺🇸North Platte, Nebraska, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Wright-Patterson Medical Center
🇺🇸Wright-Patterson AFB, Ohio, United States
Avera Research Institute
🇺🇸Sioux Falls, South Dakota, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Tulane University
🇺🇸New Orleans, Louisiana, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Mercury Street Medical Group
🇺🇸Butte, Montana, United States
Infectious Disease Specialists, PC
🇺🇸Missoula, Montana, United States
University of Alberta
🇨🇦Edmonton, Alberta, Canada
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States