High-Titer Neutralizing Plasma for West Nile Fever in Hospitalized Patients

NCT07094724 | Recruiting Phase 2 DMC

• 1 other identifier: SHEBA-25-2255-GR-CTIL
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test whether plasma containing high levels of neturalizing antibodies against West Nile virus (WNV) can help people hospitalized with severe West Nile fever recover faster and avoid serious complications. West Nile virus is spread by mosquitoes and can cause mild flu-like symptoms or, in severe cases, brain infections. Currently, there is no specific medication to treat the infection, and doctors primarily provide supportive care. In this study, patients who are sick enough to require hospitalization will receive plasma donated by people who have recovered from West Nile virus and developed high titer neutralizing antibodies against the disease. Researchers will closely monitor these patients to see how quickly their symptoms improve and whether the plasma helps reduce the risk of death or shorten hospital stays. To evaluate how well the plasma works, researchers will compare these patients to others who were infected in the past for West Nile virus but did not receive plasma. The study will also examine whether the plasma is safe to use and whether it causes any side effects. Through this research, scientists hope to determine if antibody-rich plasma could become a helpful treatment option for people with severe West Nile virus infections.

Conditions

West Nile Fever

Keywords

West Nile Fever; plasma; neuroinvasive WN disease

Outcome Measures

Primary Outcomes (1)

• All-cause mortality within 30 days post enrollment.

  0-30 days

Secondary Outcomes (9)

• MMSE score at enrollment and at 30 (±3) days post enrollment

  0-33 days

• Discharge to pre-hospitalization residence setting.

  0-90 days.

• Length of hospital stay

  0-90 days.

• Serum WNV PCR, IgG, IgM, IgA and neutralizing antibody levels at enrollment, at 7 (±3) days (if still hospitalized), and 30 (±3) days post enrollment.

  0-33 days

• WNV PCR, IgG, IgM, IgA and neutralizing antibodies levels in the CSF, at enrollment and within 48-72 (±48) hours post enrollment.

  0-7 days

Study Arms (2)

WN-neutralizing Plasma

EXPERIMENTAL

IV plasma

Biological: Plasma

historical untreated control

NO INTERVENTION

Interventions

Plasma BIOLOGICAL

administration of IV high-titer WNV-neutralizing plasma

WN-neutralizing Plasma

Eligibility Criteria

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

You may qualify if:

• Adults hospitalized due to WNF, confirmed by a positive IgM or PCR result in blood or cerebrospinal fluid (CSF).
• Symptomatic acute illness, including fever and/or neurological manifestations (headache, somnolence, confusion, seizures, personality changes, extra-pyramidal manifestations, cranial nerve palsies, etc.).
• No more than 72 hours have elapsed since collection of diagnostic sample.
• Age criteria
• Age ≥60 years OR
• Age 18-59 years with previously documented immunosuppression, including hypogammaglobulinemia, treatment with anti-CD20 agents during the last 12 months, hematologic malignancy, bone marrow transplantation, solid organ transplantation, acquired immunodeficiency syndrome (AIDS), or severe primary immunodeficiency.

You may not qualify if:

• Age \<60 years without significant immunosuppression.
• More than 72 hours have elapsed since collection of diagnostic sample.
• Pregnancy.

Sponsors & Collaborators

• Gili Regev-Yochay MD: lead

Study Sites (1)

Sheba Medical Center

Ramat Gan, Israel

RECRUITING

Related Publications (10)

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  PMID: 3558716 BACKGROUND

• Teasdale G, Maas A, Lecky F, Manley G, Stocchetti N, Murray G. The Glasgow Coma Scale at 40 years: standing the test of time. Lancet Neurol. 2014 Aug;13(8):844-54. doi: 10.1016/S1474-4422(14)70120-6.

  PMID: 25030516 BACKGROUND

• Wade DT, Collin C. The Barthel ADL Index: a standard measure of physical disability? Int Disabil Stud. 1988;10(2):64-7. doi: 10.3109/09638288809164105.

  PMID: 3042746 BACKGROUND

• Norris D, Clark MS, Shipley S. The Mental Status Examination. Am Fam Physician. 2016 Oct 15;94(8):635-641.

  PMID: 27929229 BACKGROUND

• Katzenellenbogen G, Canetti M, Margalit I, Shusterman Y, Simchovitz-Gesher A, Naveh L, Baharav N, Goldenfeld M, Belkin A, Brod M, Wieder-Finesod A, Leshem E, Magiel E, Levy I, Lustig Y, Indenbaum V, Maggio N, Dekel S, Mechnik B, Peretz Y, Barda N, Tafesh A, Yahav D, Regev-Yochay G. West Nile Virus Outbreak in Israel 2024 Compared with Previous Seasons: A Retrospective Study. Infect Dis Ther. 2025 Jul;14(7):1405-1415. doi: 10.1007/s40121-025-01140-3. Epub 2025 Apr 3.

  PMID: 40180788 BACKGROUND

• Popescu CP, Florescu SA, Hasbun R, Harxhi A, Evendar R, Kahraman H, Neuberger A, Codreanu D, Zaharia MF, Tosun S, Ceausu E, Ruta SM, Dragovac G, Pshenichnaya N, Gopatsa G, Shmaylenko O, Nagy E, Malbasa JD, Strbac M, Pandak N, Pullukcu H, Lakatos B, Cag Y, Cascio A, Coledan I, Oncu S, Erdem H. Prediction of unfavorable outcomes in West Nile virus neuroinvasive infection - Result of a multinational ID-IRI study. J Clin Virol. 2020 Jan;122:104213. doi: 10.1016/j.jcv.2019.104213. Epub 2019 Nov 11.

  PMID: 31778945 BACKGROUND

• Roberts JA, Kim CY, Hwang SA, Hassan A, Covington E, Heydari K, Lyerly M, Sejvar JJ, Hasbun R, Prasad M, Thakur KT. Clinical, Prognostic, and Longitudinal Functional and Neuropsychological Features of West Nile Virus Neuroinvasive Disease in the United States: A Systematic Review and Meta-Analysis. Ann Neurol. 2025 Jul;98(1):93-106. doi: 10.1002/ana.27220. Epub 2025 Feb 26.

  PMID: 40008684 BACKGROUND

• Chancey C, Grinev A, Volkova E, Rios M. The global ecology and epidemiology of West Nile virus. Biomed Res Int. 2015;2015:376230. doi: 10.1155/2015/376230. Epub 2015 Mar 19.

  PMID: 25866777 BACKGROUND

• Moirano G, Fletcher C, Semenza JC, Lowe R. Short-term effect of temperature and precipitation on the incidence of West Nile Neuroinvasive Disease in Europe: a multi-country case-crossover analysis. Lancet Reg Health Eur. 2024 Dec 4;48:101149. doi: 10.1016/j.lanepe.2024.101149. eCollection 2025 Jan.

  PMID: 39717226 BACKGROUND

• Erazo D, Grant L, Ghisbain G, Marini G, Colon-Gonzalez FJ, Wint W, Rizzoli A, Van Bortel W, Vogels CBF, Grubaugh ND, Mengel M, Frieler K, Thiery W, Dellicour S. Contribution of climate change to the spatial expansion of West Nile virus in Europe. Nat Commun. 2024 Feb 8;15(1):1196. doi: 10.1038/s41467-024-45290-3.

  PMID: 38331945 BACKGROUND

Related Links

• Israel Ministry of Health. West-Nile fever documented cases in Israel, 2000-2024.

MeSH Terms

Conditions

West Nile Fever

Condition Hierarchy (Ancestors)

Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Mosquito-Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Study Officials

• Gili Regev-Yochay, MD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gili Regev-Yochay, MD

CONTACT

+972526666197; gili.regev@sheba.health.gov.il

Almog Cohen-Huszti

CONTACT

+972545377537; Almog.CohenHuszti@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Sheba Pandemic Preparedness Research Institute (SPRI)

Model Details: All recruited patients will recieve high neutrlizing plasma, the intervention arm will be compared to historical controls.

Study Record Dates

• First Submitted: June 22, 2025
• First Posted: July 30, 2025
• Study Start: July 30, 2025
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: August 26, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Upon publication.
• Access Criteria: PI \& CRA

Locations

IL (1)