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Protocol Details

A Phase 1/2 Randomized, Double-Blinded, Placebo-Controlled Trial Evaluating the Immunogenicity and Safety of an Adjuvanted Epstein-Barr Virus (EBV) Glycoprotein 350 Vaccine in EBV-Seronegative Persons

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

001048-I

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 18 Years
Max Age: 25 Years

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

Infectious Mononucleosis;
Neutralizing Antibody;
Immune Response;
Herpesvirus

Recruitment Keyword(s)

None

Condition(s)

Epstein-Barr Virus Infection;
Infectious Mononucleosis;
Herpesvirus

Investigational Drug(s)

Matrix-M1 Adjuvant
EBV gp350-Ferritin Vaccine

Investigational Device(s)

None

Intervention(s)

Drug: Matrix-M1 Adjuvant
Drug: EBV gp350-Ferritin Vaccine
Other: Placebo Comparator

Supporting Site

National Institute of Allergy and Infectious Diseases

Background:

Epstein-Barr virus (EBV) causes most cases of infectious mononucleosis (mono). Mono can cause fatigue that lasts more than 6 months, and some people can have severe complications. EBV infection may also contribute to some cancers and autoimmune diseases. Currently, there are no approved therapies or vaccines for EBV infection.

Objective:

To test a vaccine against EBV.

Eligibility:

Healthy people aged 18 to 25 years.

Design:

Participants will be screened in 2 parts. They will have a blood test. If that test shows they have never had an EBV infection, they will have a second clinic visit. They will have a physical exam, with blood and urine tests. A cotton swab will be rubbed on their gums to collect saliva.

Participants will receive 2 injections into a shoulder muscle. Some will receive the EBV vaccine. Others will receive a placebo; this contains harmless salt water with no vaccine. Participants will not know which one they are getting. The 2 injections will be 30 days apart.

Participants will be asked to record any side effects or symptoms they have between visits. They can do this on paper or online.

Participants will return for a follow-up visit 60 days after the first injection. They will have follow-up visits by phone or telehealth after 5 and 8 months. They will return for a physical exam after 13 months. They may come back for an optional physical exam after 2 years.

Participants will come to the clinic if they become ill with an EBV infection during the study.

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Eligibility

INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all the following criteria:

- Aged 18 to 25 years.

- Able to provide informed consent.

- Willing to allow samples and data to be stored for future secondary research.

- Stated willingness to comply with all study procedures and availability for the duration of the active phase of the study (approximately 18 months).

- In good general health as evidenced by medical history, physical examination, and laboratory screening results.

- Willing to forgo receipt of a licensed, live vaccine in the 30 days before and 30 days after each dose of the study vaccine. Any FDA-approved or authorized inactivated and/or protein subunit, RNA, or DNA vaccine can be used >=14 days before or >=14 days after administration of the study vaccine.

- Hemoglobin within institutional normal limits, or if not, then assessed and deemed not clinically significant by PI or designee.

- White blood cell count and differential within institutional normal reference range, or if not, then deemed not clinically significant by PI or designee.

- Total lymphocyte count (lymphocyte absolute) >800 cells/microliters.

- Platelet count of 125,000 to 500,000/microliters.

- Alanine aminotransferase <1.25 x upper limit of normal.

- Participants who can get pregnant must agree to abstain from sexual activities that can result in pregnancy or use one of the following effective methods of contraception, starting 30 days before the first dose of study vaccine through 60 days after the third dose:

-- Intrauterine device (IUD) or equivalent.

-- Hormonal contraceptive (eg, consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy before the first dose of study agent). If the participant uses a contraceptive pill, patch, or ring, then a barrier method (eg, internal/external condom, cervical cap, or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity.

-- A hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy.

-- Barrier method (eg, internal/external condom, cervical cap, or diaphragm) plus spermicide used correctly during sexual intercourse.

-- A vasectomy in their monogamous sexual partner completed at least 6 months before the first dose of study vaccine.

-- Continuous abstinence.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

- Pregnant or breastfeeding, or planning to become pregnant while participating through 60 days after the third dose of study vaccine.

- Has received any of the following:

-- More than 10 days of systemic glucocorticoids (>=10 mg of prednisone or equivalent) within the 30 days prior to first dose of study agent.

-- More than 10 days of systemic immunosuppressive medications, cytotoxic medications, or immunomodulating therapy within 180 days prior to first dose of study agent.

-- Blood products, including immunoglobulins, within 120 days prior to first dose of study agent.

-- Any live attenuated vaccination within 30 days prior to first dose of study agent.

-- Investigational research agents within 30 days prior to first dose or planning to receive investigational products while on study.

-- Allergy treatment with antigen injections, unless on a maintenance schedule of shots no more frequently than once per month.

- Has any of the following:

-- Febrile illness within 14 days of the first dose of study agent.

-- Body habitus such that identification of the deltoid muscle and/or administration of vaccine into the deltoid would be compromised or if body habitus would make study inclusion not in the best interest of the participant.

-- History of serious reactions to vaccines.

-- Hereditary, acquired, or idiopathic forms of angioedema.

-- Idiopathic urticaria within the past year.

-- Asthma that is not well-controlled or that required emergency care, urgent care, hospitalization, or intubation during the past 2 years, or that requires the use of oral or intravenous steroids.

--Diabetes mellitus type 1 or type 2, excluding a history of gestational diabetes.

-- Clinically significant autoimmune disease or immunodeficiency.

-- Bleeding disorder diagnosed by doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions).

-- Significant bruising or bleeding difficulties with intramuscular injections or blood draws.

-- Malignancy that is active or treated malignancy for which there is no reasonable assurance of sustained cure or malignancy that is likely to recur during the study period.

-- Seizure disorder other than a history of 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the past 3 years.

-- Asplenia, functional asplenia, or any condition resulting in absence or removal of the spleen.

-- History of Guillain-Barre Syndrome.

-- Alcohol or drug abuse or addiction.

-- HIV infection.

-- Active hepatitis B or C infection.

-- Documented EBV infection.

- Prior enrollment in an EBV vaccine clinical trial.

- Any medical, psychiatric, or social condition that, in the judgement of the investigator, is a contraindication to protocol participation or impairs the participant s ability to give informed consent.

Co-enrollment guidelines:

Co-enrollment in other studies is restricted, other than enrollment on observational studies. Consideration for co-enrollment in trials evaluating the use of a licensed medication will require the approval of the PI or sponsor medical monitor (SMM). Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the PI or SMM.


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Citations:

Kanekiyo M, Bu W, Joyce MG, Meng G, Whittle JR, Baxa U, Yamamoto T, Narpala S, Todd JP, Rao SS, McDermott AB, Koup RA, Rossmann MG, Mascola JR, Graham BS, Cohen JI, Nabel GJ. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site. Cell. 2015 Aug 27;162(5):1090-100. doi: 10.1016/j.cell.2015.07.043. Epub 2015 Aug 13. PMID: 26279189; PMCID: PMC4757492.

Cohen JI. Epstein-barr virus vaccines. Clin Transl Immunology. 2015 Jan 23;4(1):e32. doi: 10.1038/cti.2014.27. Erratum in: Clin Transl Immunology. 2015 Apr;4(4):e36. PMID: 25671130; PMCID: PMC4318489.

Cohen JI, Fauci AS, Varmus H, Nabel GJ. Epstein-Barr virus: an important vaccine target for cancer prevention. Sci Transl Med. 2011 Nov 2;3(107):107fs7. doi: 10.1126/scitranslmed.3002878. PMID: 22049067; PMCID: PMC3501269.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Jessica R. Durkee-Shock, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CLINICAL CENTER BG RM 6D44D
10 CENTER DR
BETHESDA MD 20892
(301) 761-6539
jessica.durkee-shock@nih.gov

Krista S. Gangler, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 9N214
10 Center Drive
Bethesda, Maryland 20892
(301) 761-6437
krista.gangler@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT05683834

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