IVIG - West Nile Encephalitis: Safety and Efficacy

NCT00068055 | Completed Phase 1

• 2 other identifiers: 03-107CASG 210
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 69

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.

Conditions

West Nile Virus

Keywords

West Nile Virus, encephalitis, myelitis, immunoglobulin G

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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.

• 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.

• Mortality alone among confirmed WNV patients.

  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.

Study Arms (3)

1

EXPERIMENTAL

60 subjects to receive Omr-IgG-am.

Drug: Omr-lgG-am

2

ACTIVE COMPARATOR

20 subjects to receive Polygam® S/D (IVIG).

Drug: Polygam® S/D

3

PLACEBO COMPARATOR

20 subjects to receive normal saline.

Drug: Placebo

Interventions

Omr-lgG-am DRUG

Omr-IgG-am™ 5% is provided in 100 ml bottles (5.0 grams) as a sterile solution containing 5% protein, 10% maltose and water for injection. This product is licensed in Israel, but not in the US.

1

Polygam® S/D DRUG

Polygam® S/D is a solvent/detergent treated, sterile, freeze-dried preparation of highly purified immunoglobulin G (IgG) derived from large pools of human plasma. When reconstituted (5%) with the supplied diluent (sterile water for injection, USP) Polygam® S/D contains approximately 50mg of protein per ml (approximately 90% is gamma globulin); 3mg/ml human albumin, 22.5 mg/ml glycine, 20 mg/ml glucose, 2mlg/ml polyethylene glycol (PEG), 1 mcg/ml tri-nbutyl phosphate, 1 mcg/ml octoxynol 9, and 100 mcg/ml polysorbate 80.

2

Placebo DRUG

Normal Saline.

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (69)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-2050, United States

Location

University of South Alabama Medical Center

Mobile, Alabama, 36617, United States

Location

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

University of Arkansas

Little Rock, Arkansas, 72205, United States

Location

Enloe Medical Center

Chico, California, 95926, United States

Location

Seton Medical Center

Daly City, California, 94015, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Kaiser Permanente South Bay Medical Center

Harbor City, California, 90710, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California Irvine

Orange, California, 92868-3298, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California San Francisco

San Francisco, California, 94114, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Santa Rosa Kaiser Medical

Santa Rosa, California, 95403, United States

Location

Exempla St. Joseph Hospital

Denver, Colorado, 80218, United States

Location

University of Colorado

Denver, Colorado, 80262, United States

Location

George Washington University Medical Center

Washington D.C., District of Columbia, 20037, United States

Location

Idaho Falls Infectious Diseases, PLLC

Idaho Falls, Idaho, 83404, United States

Location

Loyola University

Maywood, Illinois, 60153, United States

Location

Indiana University

Indianapolis, Indiana, 46202-5124, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Via Christi Regional Medical Center

Wichita, Kansas, 67214, United States

Location

University of Kentucky

Lexington, Kentucky, 40536-0084, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

National Institutes of Health

Bethesda, Maryland, 20892-1662, United States

Location

University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110-1093, United States

Location

Saint Louis University

St Louis, Missouri, 63110, United States

Location

Mercury Street Medical Group

Butte, Montana, 59701, United States

Location

Infectious Disease Specialists, PC

Missoula, Montana, 59802, United States

Location

Central Nebraska Medical Clinic

Broken Bow, Nebraska, 68822, United States

Location

McCook Clinic, PC

McCook, Nebraska, 69001, United States

Location

Great Plains Regional Medical Center

North Platte, Nebraska, 69101, United States

Location

VA Medical Center - Omaha

Omaha, Nebraska, 68105, United States

Location

Creighton University

Omaha, Nebraska, 68131, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7630, United States

Location

Clara Maass Medical Center

Belleville, New Jersey, 07109, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Flushing Hospital Medical Center

Flushing, New York, 11355, United States

Location

St. Alexius Medical Center

Bismarck, North Dakota, 58506, United States

Location

Dakota Clinic at Innovis

Fargo, North Dakota, 58103, United States

Location

MeritCare Hospital

Fargo, North Dakota, 58122, United States

Location

Trinity Health - Hospital

Minot, North Dakota, 58701, United States

Location

University Hospital

Cincinnati, Ohio, 45219, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

University of Toledo

Toledo, Ohio, 43614, United States

Location

Wright-Patterson Medical Center

Wright-Patterson AFB, Ohio, 45433, United States

Location

Legacy Good Samaritan

Portland, Oregon, 97210, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18103, United States

Location

The Reading Hospital and Medical Center

West Reading, Pennsylvania, 19611, United States

Location

Memorial Hospital of RI

Pawtucket, Rhode Island, 02860, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Infectious Disease Consultations - Rapid City

Rapid City, South Dakota, 57701, United States

Location

Avera Research Institute

Sioux Falls, South Dakota, 57105, United States

Location

Vanderbilt University

Nashville, Tennessee, 37205, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390-8884, United States

Location

The University of Texas Medical Branch

Galveston, Texas, 77555-0167, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center

San Antonio, Texas, 78229-3900, United States

Location

Wilford Hall Medical Center

San Antonio, Texas, 78236, United States

Location

The University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

University of Calgary

Calgary, Alberta, T2N4N, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3E 0W3, Canada

Location

MeSH Terms

Conditions

Encephalitis; Myelitis

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases; Central Nervous System Infections; Infections; Spinal Cord Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 4, 2003
• First Posted: September 8, 2003
• Study Start: September 1, 2003
• Primary Completion: December 1, 2006
• Study Completion: December 1, 2006
• Last Updated: February 7, 2011

Record last verified: 2009-07

Locations

US (66); CA (3)