Clinical trial NCT06590207: Convalescent Plasma for the Treatment of Patients With WNV - a Double- Blind Randomized Controlled Study
Official title: Administering Convalescent Plasma Rich With Neutralizing Abs. to Hospitalized Adults With WNV - a Double-blind Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: West Nile Fever With Neurologic Manifestation (Diagnosis)
West Nile Fever Without Complications
Keywords: WNV; Neutralizing Abs; Convalescent plasma; neuroinvasive
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2024-09-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: double-blind randomized controlled study.
Primary purpose: TREATMENT

Brief summary: Name of the study:

Administering neutralizing convalescent plasma to hospitalized patients with West Nile fever - a double-blind randomized controlled study.

The purpose of this study is to test the safety and effectiveness of giving blood plasma from convalescents rich in neutralizers as treatment against West Nile fever.

Detailed description: The study is performed in Sheba Medical Center ( and will be expanded in the soon future to other Medical centers in Israel).

Hospitalized patients diagnosed by blood/CSF PCR or IgM, with West Nile Virus will be recruited to the study.

After signing an informed consent they will be randomized (2:1) to receive either blood plasma rich in neutralizing antibodies or saline as placebo.

Number of participants in this center: 130 Age range: 60 years old and older, 18-60 years old with immunosuppression.

Inclusion criteria:

* Hospitalized patients with positive WNV-PCR with fever/neurological symptoms, and 72 hours have not yet passed since the positive result.
* Age 60 or older.
* Age over 18 and younger than 60 with immunosuppression (hypogammaglobulinemia, solid organ transplants, bone marrow transplants, hemato-oncological malignancies).

Exclusion criteria:

* Age younger than 60 without immunosuppression.
* More than 72 hours have passed since the diagnosis of West Nile fever.
* Pregnant women.

Reference to the inclusion of pregnant women, special populations - children and those lacking judgment- not relevant: excludes pregnant women and special populations.

The duration of the medical trial includes the follow-up period after the trial:

The duration of the treatment is one day, single dose of plasma/saline. The follow-up period is 90 days.

The clinical follow-up plan (during and at the end of the treatment):

A total of 10 visits will be conducted. On day 1, the following will be performed: screening, Medical history \& Physical examination, IV Convalescent Plasma vs. Saline, Urine and blood for PCR, functional \& neurologic assesment, IgG and IgM from serum, blood test for CBC \& renal function.

On day 2-7 and 30 and 90, AE will be collected. On day 3, 5, 7 Urine and blood for PCR will be collected. Neurologic assesment will be conducted on all visits. Serology will be collected also on day 30 and 90.

After discharge, a follow-up visit will be performed either by a visit to the clinic or via phone call.

Eligibility criteria: Inclusion Criteria:

* Hospitalized patients with positive WNV-PCR with fever/neurological symptoms, and 72 hours have not yet passed since the positive result.
* Age 60 or older.
* Age over 18 and younger than 60 with immunosuppression (hypogammaglobulinemia, solid organ transplants, bone marrow transplants, hemato-oncological malignancies).

Exclusion Criteria:

* Age younger than 60 without immunosuppression.
* More than 72 hours have passed since the diagnosis of West Nile fever.
* Pregnant women. Criteria for exclusion from the experiment: none Reference to the inclusion of pregnant women, special populations - children and those lacking judgment- not relevant: excludes pregnant women and special populations

Primary outcomes:
measure: Unfavorable outcom = Composite outcome of mortality or functional deterioration on day 30
timeFrame: day 28-32
Secondary outcomes:
measure: unfavorable outcome on day 90
timeFrame: day 88-92
measure: Serious adverse events
timeFrame: day 2-32
measure: Mortality
timeFrame: day 28-92
measure: Functional deterioration by day 30 & 90
timeFrame: 28-92 days
measure: Neurologic deterioration by day 30 & 90
timeFrame: 28-92 days
Other outcomes:
measure: Mechanical ventilation
timeFrame: 2-92 days
measure: ICU
timeFrame: 2-92days
Locations:
city: Ramat-Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Sheba research grants and academic collaboration director
name: Michaela Va Smilovici-Ofir, Phd
role: STUDY_CHAIR
References:
citation: Bassal R, Shohat T, Kaufman Z, Mannasse B, Shinar E, Amichay D, Barak M, Ben-Dor A, Bar Haim A, Cohen D, Mendelson E, Lustig Y. The seroprevalence of West Nile Virus in Israel: A nationwide cross sectional study. PLoS One. 2017 Jun 16;12(6):e0179774. doi: 10.1371/journal.pone.0179774. eCollection 2017.
citation: Planitzer CB, Modrof J, Kreil TR. West Nile virus neutralization by US plasma-derived immunoglobulin products. J Infect Dis. 2007 Aug 1;196(3):435-40. doi: 10.1086/519392. Epub 2007 Jun 18.
citation: Srivastava R, Ramakrishna C, Cantin E. Anti-inflammatory activity of intravenous immunoglobulins protects against West Nile virus encephalitis. J Gen Virol. 2015 Jun;96(Pt 6):1347-1357. doi: 10.1099/vir.0.000079. Epub 2015 Feb 9.
citation: Gnann JW Jr, Agrawal A, Hart J, Buitrago M, Carson P, Hanfelt-Goade D, Tyler K, Spotkov J, Freifeld A, Moore T, Reyno J, Masur H, Jester P, Dale I, Li Y, Aban I, Lakeman FD, Whitley RJ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Lack of Efficacy of High-Titered Immunoglobulin in Patients with West Nile Virus Central Nervous System Disease. Emerg Infect Dis. 2019 Nov;25(11):2064-2073. doi: 10.3201/eid2511.190537.
citation: Mbonde AA, Gritsch D, Harahsheh EY, Kasule SN, Hasan S, Parsons AM, Zhang N, Butterfield R, Shiue H, Norville KA, Reynolds JL, Vikram HR, Chong B, Grill MF. Neuroinvasive West Nile Virus Infection in Immunosuppressed and Immunocompetent Adults. JAMA Netw Open. 2024 Mar 4;7(3):e244294. doi: 10.1001/jamanetworkopen.2024.4294.