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IVIG - West Nile Encephalitis: Safety and Efficacy

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on May 11, 2007
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: West Nile Virus

Intervention: Omr-lgG-am (Drug); Polygam S/D (Drug)

Phase: Phase 1/Phase 2

Status: No longer recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Summary

This study will look at the safety and effectiveness of an experimental treatment 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 that do not fight infections well. WNV can cause problems such as headaches, fever, muscle weakness, coma, and death. The study investigators believe that 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 volunteers, 18 years of age of older, will participate in this study for about 3 months and have: study medicines given through an IV catheter (small tube placed in a blood vessel in the arm); hospital stay for several days; up to 5 additional study visits; blood samples collected; MRI pictures of the brain and spinal cord; and neurological, muscle, and heart activity tests.

Clinical Details

Official title: A Phase I/II Randomized, Placebo-Controlled Trial to Assess the Safety and Efficacy of Intravenous Immunoglobulin G (OMR-IGG-AM) Containing High Anti-West Nile Virus Antibody Titers in Patients With, or at High Risk for Progression to West Nile Virus (WNV) Encephalitis and/or Myelitis

Study design: Interventional, Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

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.

Eligibility

Minimum age: 18 Years. Gender(s): 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 >= 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 >= 4 per cubic mm corrected for significant red blood cell contamination.

- Ratio of CSF: plasma glucose of >= 40% (CSF glucose / plasma glucose >= 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 >= 3 of the following findings during the preceding <= 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 >= 40 years, or

- Age >= 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 >= 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, 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

Locations and Contacts

University of Alabama at Birmingham, Birmingham, Alabama 35294-2050, United States

University of South Alabama Medical Center, Mobile, Alabama 36617, United States

University of Alberta, Edmonton, Alberta T6G 2B7, Canada

University of Calgary, Calgary, Alberta T2N 4N1, Canada

St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, United States

Mayo Clinic Hospital, Phoenix, Arizona 85054, United States

University of Arizona Health Sciences Center, Tucson, Arizona 85724, United States

University of Arkansas, Little Rock, Arkansas 72205, United States

Santa Rosa Kaiser Medical, Santa Rosa, California 95403, United States

Seton Medical Center, Daly City, California 94015, United States

California Pacific Medical Center, San Francisco, California 94115, United States

University of California Irvine, Orange, California 92868-3298, United States

University of California San Francisco, San Francisco, California 94143-0654, United States

Kaiser Permanente South Bay Medical Center, Harbor City, California 90710, United States

City of Hope National Medical Center, Duarte, California 91010, United States

University of Southern California, Los Angeles, California 90033, United States

University of California Davis Medical Center, Sacramento, California 95817, United States

University of Colorado, Denver, Colorado 80262, United States

Exempla St. Joseph Hospital, Denver, Colorado 80218, United States

The George Washington University Medical Center, Washington, District of Columbia 20037, United States

Idaho Falls Infectious Diseases, PLLC, Idaho Falls, Idaho 83404, United States

Loyola University, Maywood, Illinois 60153, United States

Indiana University, Indianapolis, Indiana 46202-5124, United States

University of Kansas Medical Center, Kansas City, Kansas 66160, United States

Via Christi Regional Medical Center, Wichita, Kansas 67214, United States

University of Kentucky, Lexington, Kentucky 40536-0084, United States

Louisiana State University Health Sciences Center, Shreveport, Louisiana 71103, United States

Tulane University, New Orleans, Louisiana 70112, United States

University of Manitoba, Winnipeg, Manitoba R3E 0W3, Canada

Johns Hopkins University, Baltimore, Maryland 21287, United States

National Institutes of Health, Bethesda, Maryland 20892-1662, United States

Wayne State University, Detroit, Michigan 48201, United States

University of Michigan, Ann Arbor, Michigan 48105, United States

Washington University in St. Louis, Saint Louis, Missouri 63110-1093, United States

Saint Louis University, St. Louis, Missouri 63110, United States

Infectious Disease Specialists, PC, Missoula, Montana 59802, United States

Mercury Street Medical Group, Butte, Montana 59701, United States

University of Nebraska Medical Center, Omaha, Nebraska 68198-7630, United States

Great Plains Regional Medical Center, North Platte, Nebraska 69101, United States

VA Medical Center - Omaha, Omaha, Nebraska 68105, United States

Central Nebraska Medical Clinic, Broken Bow, Nebraska 68822, United States

Creighton University, Omaha, Nebraska 68131, United States

McCook Clinic, PC, McCook, Nebraska 69001, United States

Clara Maass Medical Center, Belleville, New Jersey 07109, United States

University of New Mexico, Albuquerque, New Mexico 87106, United States

Flushing Hospital Medical Center, Flushing, New York 11355, United States

Trinity Health - Hospital, Minot, North Dakota 58701, United States

St. Alexius Medical Center, Bismarck, North Dakota 58501, United States

MeritCare Hospital, Fargo, North Dakota 58122, United States

Dakota Clinic at Innovis, Fargo, North Dakota 58103, United States

University Hospital, Cincinnati, Ohio 45219, United States

University of Toledo, Toledo, Ohio 43614, United States

Wright-Patterson Medical Center, Wright-Patterson AFB, Ohio 45433, United States

University Hospitals of Cleveland, Cleveland, Ohio 44106, United States

Legacy Good Samaritan, Portland, Oregon 97210, United States

Lehigh Valley Hospital, Allentown, Pennsylvania 18103, United States

The Reading Hospital and Medical Center, West Reading, Pennsylvania 19611, United States

Memorial Hospital of RI, Pawtucket, Rhode Island 02860, United States

Rhode Island Hospital, Providence, Rhode Island 02903, United States

Avera Research Institute, Sioux Falls, South Dakota 57105, United States

Infectious Disease Consultations - Rapid City, Rapid City, South Dakota 57701, United States

Vanderbilt University, Nashville, Tennessee 37205, United States

The University of Texas Health Science Center at Houston, Houston, Texas 77030, United States

The University of Texas Health Science Center, San Antonio, Texas 78229-3900, United States

The University of Texas Southwestern Medical Center, Dallas, Texas 75390-8884, United States

The University of Texas Health Center at Tyler, Tyler, Texas 75708, United States

The University of Texas Medical Branch, Galveston, Texas 77555-0167, United States

Wilford Hall Medical Center, Lackland AFB, Texas 78236, United States

University of Virginia, Charlottesville, Virginia 22908, United States

Additional Information

Starting date: September 2003
Ending date: December 2006
Last updated: April 26, 2007

Page last updated: May 11, 2007

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