IVIG – West Nile encephalitis: Safety and Efficacy

Primary

To assess and characterize the safety and tolerability of Omr-IgG-am in a population of hospitalized patients with confirmed or suspected WNV disease

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

Conditions

West Nile Fever (WNV)

Study Type

Interventional

Study Design

udy Design: Treatment, Randomized, Single Group Assignment

Further Details

SecondaryTo assess pharmacokinetics of specific anti-West Nile antibodies following intravenous administration of Omr-IgG-am;To estimate efficacy of Omr-IgG-am in reducing morbidity and mortality, for patients with known or suspected WNV infection who receive WNV specific IVIg versus similar patients who receive either placebo; To further characterize the natural history of severe WNV infection.Investigators will assess whether Omr-IgG-am, intravenous immunoglobulin (IVIg) containing antibodies specific for West Nile virus (WNV), is safe and well-tolerated in patients with suspected or confirmed 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 confirmed 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, Polygam S/D (IVIG containing no anti-WNV antibodies) or 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 or Polygam S/D or a comparable volume of saline. The second cohort will receive 1 gram/kg of either preparation or saline. All patients will be followed for safety, natural history and efficacy. A subset of patients will have pharmacokinetics 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.

Study Start

Eligibility & Criteria

Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both Criteria INCLUSION CRITERIA: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 4 per mm3 corrected for significant red blood cell contamination: Ratio of CSF: plasma glucose of 40% (CSF glucose / plasma glucose ≥ 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 defined by occurrence of ≥ 3 of the following findings during the preceding ≤ 7 days: o Diarrhea o Headache o Fever > 38�C o Nausea and/or vomiting o Myalgias and/or arthralgias o Nuchal rigidity o Macular or papular rash o New neurological abnormality (not suggestive of encephalitis or myelitis) AND A risk factor for the development of WNV neurologic disease as defined by: o 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. 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 80000/mm(3), Hematocrit greater than 55 percent, platelet count greater than 700000/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, cardiovascular accident, or other infectious disease including another flavivirus). Pregnant or breastfeeding (negative serum or urine pregnancy test required within the previous 72 hours if the 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 the treatment of WNV or hepatitis within 15 days prior to study entry. Known history of hypersensitivity to maltose

Total Enrolment

100

Contact Details

[1] National Institute of Allergy and Infectious Diseases (NIAID)