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West Nile VirusPhase 1/2NCT00068055

IVIG - West Nile Encephalitis: Safety and Efficacy

A Phase 1/2 study testing Omr-lgG-am and Polygam® S/D in people with West Nile Virus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 69 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
West Nile Virus
What is being tested?
Omr-lgG-am and Polygam® S/D
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
62 participants
Where
69 sitesin 2 countries
Study dates
Sep 2003to Dec 2006
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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:
Show all 25Show fewer
  • 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
  • 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)

Who cannot join

  • 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

Trial locations and contacts

69 sites in 2 countries.

69 sites in 2 countries

United States66 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87106

  • Lehigh Valley Hospital

    Allentown, Pennsylvania, 18103

  • University of Michigan

    Ann Arbor, Michigan, 48105

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Clara Maass Medical Center

    Belleville, New Jersey, 07109

  • National Institutes of Health

    Bethesda, Maryland, 20892-1662

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-2050

  • St. Alexius Medical Center

    Bismarck, North Dakota, 58506

  • Central Nebraska Medical Clinic

    Broken Bow, Nebraska, 68822

  • Mercury Street Medical Group

    Butte, Montana, 59701

  • University of Virginia

    Charlottesville, Virginia, 22908

  • Enloe Medical Center

    Chico, California, 95926

  • University Hospital

    Cincinnati, Ohio, 45219

  • University Hospitals of Cleveland

    Cleveland, Ohio, 44106

  • The University of Texas Southwestern Medical Center

    Dallas, Texas, 75390-8884

  • Seton Medical Center

    Daly City, California, 94015

  • Exempla St. Joseph Hospital

    Denver, Colorado, 80218

  • University of Colorado

    Denver, Colorado, 80262

  • Wayne State University

    Detroit, Michigan, 48201

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Dakota Clinic at Innovis

    Fargo, North Dakota, 58103

  • MeritCare Hospital

    Fargo, North Dakota, 58122

  • Flushing Hospital Medical Center

    Flushing, New York, 11355

  • The University of Texas Medical Branch

    Galveston, Texas, 77555-0167

  • Kaiser Permanente South Bay Medical Center

    Harbor City, California, 90710

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • Idaho Falls Infectious Diseases, PLLC

    Idaho Falls, Idaho, 83404

  • Indiana University

    Indianapolis, Indiana, 46202-5124

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of Kentucky

    Lexington, Kentucky, 40536-0084

  • University of Arkansas

    Little Rock, Arkansas, 72205

  • University of Southern California

    Los Angeles, California, 90033

  • Loyola University

    Maywood, Illinois, 60153

  • McCook Clinic, PC

    McCook, Nebraska, 69001

  • Trinity Health - Hospital

    Minot, North Dakota, 58701

  • Infectious Disease Specialists, PC

    Missoula, Montana, 59802

  • University of South Alabama Medical Center

    Mobile, Alabama, 36617

  • Vanderbilt University

    Nashville, Tennessee, 37205

  • Tulane University

    New Orleans, Louisiana, 70112

  • Great Plains Regional Medical Center

    North Platte, Nebraska, 69101

  • VA Medical Center - Omaha

    Omaha, Nebraska, 68105

  • Creighton University

    Omaha, Nebraska, 68131

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198-7630

  • University of California Irvine

    Orange, California, 92868-3298

  • Memorial Hospital of RI

    Pawtucket, Rhode Island, 02860

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • Legacy Good Samaritan

    Portland, Oregon, 97210

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Infectious Disease Consultations - Rapid City

    Rapid City, South Dakota, 57701

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • The University of Texas Health Science Center

    San Antonio, Texas, 78229-3900

  • Wilford Hall Medical Center

    San Antonio, Texas, 78236

  • University of California San Francisco

    San Francisco, California, 94114

  • California Pacific Medical Center

    San Francisco, California, 94115

  • Santa Rosa Kaiser Medical

    Santa Rosa, California, 95403

  • Avera Research Institute

    Sioux Falls, South Dakota, 57105

  • Washington University in St. Louis

    St Louis, Missouri, 63110-1093

  • Saint Louis University

    St Louis, Missouri, 63110

  • University of Toledo

    Toledo, Ohio, 43614

  • University of Arizona Health Sciences Center

    Tucson, Arizona, 85724

  • The University of Texas Health Science Center at Tyler

    Tyler, Texas, 75708

  • George Washington University Medical Center

    Washington D.C., District of Columbia, 20037

  • The Reading Hospital and Medical Center

    West Reading, Pennsylvania, 19611

  • Via Christi Regional Medical Center

    Wichita, Kansas, 67214

  • Wright-Patterson Medical Center

    Wright-Patterson AFB, Ohio, 45433

Other trials in United States

Canada3 sites

  • University of Calgary

    Calgary, Alberta, T2N4N

  • University of Alberta

    Edmonton, Alberta, T6G 2B7

  • University of Manitoba

    Winnipeg, Manitoba, R3E 0W3

Other trials in Canada

About this study

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

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.

Read the 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.

Conditions
West Nile Virus
Being tested
Omr-lgG-am, Polygam® S/D, Placebo
Keywords
West Nile Virus, encephalitis, myelitis, immunoglobulin G
Medical subject headings
Encephalitis, Myelitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Omr-lgG-amDrug

    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.

  • Polygam® S/DDrug

    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.

  • PlaceboDrug

    Normal Saline.

Study groups in NCT00068055
Study groupRoleWhat they receive
1Experimental60 subjects to receive Omr-IgG-am.
Receives: Drug: Omr-lgG-am
2Active comparator20 subjects to receive Polygam® S/D (IVIG).
Receives: Drug: Polygam® S/D
3Placebo comparator20 subjects to receive normal saline.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Duration of study.

Secondary outcomes (6)

  1. Pharmacokinetics of specific anti-WNV antibodies as measured by ELISA and PRNT methods.

    Measured: 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.

  2. 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.

    Measured: At 3 months.

  3. 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.

    Measured: At 3 months.

  4. Mortality alone among confirmed WNV patients.

    Measured: At 3 months.

  5. Combined morbidity and mortality in treatment versus placebo groups for all (including those without WNV infection) subjects by intention to treat analysis.

    Measured: At 3 months.

  6. 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.

    Measured: At 3 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2003 (estimated)
  2. Study startSep 2003
  3. Primary completionDec 2006
  4. Study completionDec 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00068055
Sponsor's protocol ID
03-107
Other IDs
CASG 210
Status last verified
Jul 2009
First submitted
4 Sep 2003
Last updated
7 Feb 2011
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Omr-lgG-am and Polygam® S/D in people with West Nile Virus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 69 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 69 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Duration of study.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00068055.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2011.

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