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Safety and Immunogenicity of an Epstein-Barr Virus (EBV) gp350-Ferritin Nanoparticle Vaccine in Healthy Adults With or Without EBV Infection

Primary Purpose

EBV, Epstein-Barr Virus Infection, Infectious Mononucleosis

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
EBV gp350-Ferritin Vaccine
Matrix-M1
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for EBV focused on measuring Infectious Mononucleosis, Neutralizing Antibody, CD4+ T cell response, Immune Response

Eligibility Criteria

18 Years - 29 Years (Adult)All SexesAccepts Healthy Volunteers
  • INCLUSION CRITERIA:

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

  1. 18 to 29 years old
  2. Screening procedures and evaluations performed no more than 30 days prior to scheduled administration of the first vaccine dose.
  3. Ability of subject to understand and the willingness to sign a written informed consent document.
  4. Stated willingness to comply with all study procedures and availability for the duration of the active phase of the study (approximately 18 months)
  5. Willingness to allow storage of blood and saliva for future research.
  6. In good general health as evidenced by medical history, physical examination, and laboratory screening result.
  7. Subject is willing to forgo receipt of a licensed, live vaccine in the 30 days preceding each dose of vaccine or in the 30 days following each dose of vaccine. An FDA-approved inactivated, subunit or replication-defective vaccine (such as COVID-19, influenza,

    tetanus etc.) and/or a COVID-19 vaccine approved under emergency use authorization can be used >=14 days before or >=14 days after administration of the study vaccine.

  8. For females of reproductive potential who are sexually active with a male partner: use of highly effective continuous contraception for at least 30 days prior to Day 0 and agreement to continue use until 60 days after the last dose of vaccine.
  9. For males who are sexually active with partners of child-bearing potential: use of highly effective continuous contraception from Day 0 and agreement to continue use until 30 days after the last dose of vaccine.

    Contraceptive requirements: Because the effects of EBV gp350-Ferritin vaccine on the developing human fetus are unknown, sexually active female participants of childbearing potential must agree to use highly effective contraception as outlined below before study entry and until 60 days after the last dose of vaccine. Females of childbearing potential must have a negative pregnancy test before receiving each dose of the EBV gp350-Ferritin vaccine. During the course of the study, if a participant becomes pregnant or suspects they are pregnant, then they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are:

    • Intrauterine device (IUD) or equivalent
    • Hormonal contraceptive (e.g. consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy prior to dosing). If the participant uses a contraceptive pill, path, or ring, then a barrier method (e.g. male/female condom, cap or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity.
    • A stable, long-term monogamous relationship with a partner who does not pose any potential pregnancy risk, e.g. has undergone a vasectomy at least 6 months prior to the first dose of vaccine or is of the same sex as the participant.
    • A hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy

    Acceptable forms of contraception for male participants include one of the following:

    • Condom plus spermicide, used before or during sexual intercourse, even if the female partner uses a contraceptive pill, patch, or ring
    • A vasectomy completed at least 6 months before the first dose of vaccine
    • Continuously and completely abstaining from sexual intercourse with a female with child-bearing potential from the first dose of vaccine until 30 days after the last dose.

    Acceptable contraception for female partners with child-bearing potential of male study participants include one of the following:

    • IUD or equivalent
    • Hormonal contraceptive (e.g. pill, patch, ring, implant or an injection used consistently and that has reached full effect prior to the first dose of vaccine)
    • Hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy

    Laboratory Criteria within 30 days or less prior to enrollment:

  10. Hemoglobin within institutional normal limits or if not, then assessed and deemed not clinically significant by PI or designee
  11. White blood cell (WBC) count and differential either within institutional normal reference range or if not then assessed and deemed not clinically significant by PI or designee
  12. Total lymphocyte count (lymphocyte absolute) >= 800 cells/mm3 (0.8 K/mcL)
  13. Platelet count equal to 125,000 - 500,000/Mm^3 (125-500 K/mcL)
  14. Alanine aminotransferase (ALT) <= 1.25x upper limit of normal (ULN)
  15. Serum IgG > 600 mg/dL
  16. Negative human immunodeficiency virus (HIV) test.

EXCLUSION CRITERIA:

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

  1. Women who are breastfeeding or planning to become pregnant while participating through 60 days after the last dose of vaccine
  2. Participant has received any of the following:

    1. More than 10 days of systemic immunosuppressive medications (>=10 mg prednisone dose or its equivalent) or cytotoxic medication within the 30 days prior to first dose of vaccine or immunomodulating therapy within 180 days prior to first dose of vaccine.
    2. Blood products, including immunoglobulin products, within 120 days prior to first dose of vaccine
    3. Any live attenuated vaccination within 30 days prior to first dose of vaccine
    4. Medically indicated subunit inactivated or replication-defective vaccines, e.g. influenza, pneumococcal, COVID-19 within 14 days of the first dose of vaccine.
    5. Investigational research agents within 30 days prior to first dose or planning to receive investigational products while on study
    6. Allergy treatment with antigen injections, unless on a maintenance schedule of shots no more frequently than once per month.
  3. Participant has any of the following:

    1. Febrile illness within 14 days of the first dose of vaccine
    2. Body Mass Index (BMI) >36
    3. Serious reactions to vaccines
    4. Hereditary, acquired, or idiopathic forms of angioedema
    5. Idiopathic urticaria within the past year
    6. Asthma that is not well-controlled or required emergent care, urgent care, hospitalization or intubation during the past two years or that requires the use of oral or intravenous steroids
    7. Diabetes mellitus type 1 or type 2, excluding a history of gestational diabetes
    8. Clinically significant autoimmune disease or immunodeficiency
    9. Hypertension that is not well-controlled
    10. Thyroid disease that is not well-controlled
    11. Bleeding disorder diagnosed by doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
    12. Significant bruising or bleeding difficulties with IM injections or blood draws
    13. 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
    14. 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
    15. Asplenia, functional asplenia or any condition resulting in absence or removal of the spleen.
    16. History of Guillain-Barre Syndrome
    17. Alcohol or drug abuse or addiction
  4. 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.

Sites / Locations

  • National Institutes of Health Clinical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EBV gp_350 Ferritin Vaccination

Arm Description

Adult participants with or without prior EBV infection will receive 3 doses of vaccine

Outcomes

Primary Outcome Measures

Local and systemic reactogenicity; unsolicited adverse events; serious adverse events; change in neutralizing antibody responses to EBV
-Local reactogenicity: pain, tenderness, redness, bruising, swelling; Systemic reactogenicity symptoms: headache, muscle pain, fatigue, chills, oral temperature, joint pain, nausea/ vomiting, diarrhea; Change in log10 antibody response to EBV from baseline to 1 month after third dose of vaccine(Day 210) as measured by neutralization assay.

Secondary Outcome Measures

Change in antibody responses to EBV gp350; change in CD4+ T cell responses to EBV gp350
-Change in log10 antibody response to EBV from baseline to 1 month after third vaccine dose measured by a luciferase immunoprecipitation assay; --Change in log10 CD4+ T cell response from baseline to one month after third dose measured by an intracellular cytokine staining assay.

Full Information

First Posted
November 25, 2020
Last Updated
October 20, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT04645147
Brief Title
Safety and Immunogenicity of an Epstein-Barr Virus (EBV) gp350-Ferritin Nanoparticle Vaccine in Healthy Adults With or Without EBV Infection
Official Title
Phase 1 Study of the Safety and Immunogenicity of an Epstein-Barr Virus (EBV)gp350- Ferritin Nanoparticle Vaccine in Healthy Adults With or Without EBV Infection
Study Type
Interventional

2. Study Status

Record Verification Date
October 19, 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 29, 2022 (Actual)
Primary Completion Date
July 1, 2025 (Anticipated)
Study Completion Date
July 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Background: Epstein-Barr virus (EBV) causes most cases of infectious mononucleosis (mono). Up to 1 in 10 people who get mono can have fatigue that lasts more than 6 months. One out of 100 people can have severe complications. EBV is also associated with several types of cancer. Researchers want to test an EBV vaccine. Objective: To test the safety of and immune response to a new vaccine against EBV. Eligibility: Healthy adults ages 18-29 Design: Participants will be screened with a medical history and physical exam. They will give a blood sample. Screening tests will be repeated during the study. Participants will get a dose of the study vaccine as an injection in a muscle in the upper arm. They will be observed for 30 to 60 minutes. Blood pressure, heart rate, breathing rate, and temperature will be checked. The injection site will be examined. Participants will get a diary card. They will write down any side effects they have after the vaccine dose, or they may use an electronic diary card. Participants will be asked to write down or enter any important medical events that may occur at any time during the study. Participants will get a vaccine dose at 2 more study visits. They will have 4 follow-up visits at different times after a vaccine dose. Participants will have 6 telephone calls in between the in-person visits. They will also have 1 telephone call 1 year after the third dose of vaccine. If possible, this visit can occur in person. Participation will last about 18 months. There is an optional in-person visit or telephone call 2 years after the third dose of vaccine.
Detailed Description
Study Description: Phase 1 study to evaluate the safety and immunogenicity of a 3-dose vaccination regimen of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Based on data reported in animal studies, our hypothesis is that this EBV vaccine will be safe and will induce a potent EBVgp350-specific immune response. Twenty EBV seropositive participants and 20 EBV seronegative participants will receive 3 doses of vaccine at 0, 1, and 6 months. Subjects will be followed until 12 months after the third dose of vaccine with an option to be followed for an additional year. Objectives: Primary objective: To determine the safety and immunogenicity of an adjuvanted EBV gp350- Ferritin vaccine administered as 3 intramuscular injections to healthy adults with or without prior EBV infection. Secondary objective: To further evaluate the immunogenicity of an adjuvanted EBV gp350-Ferritin vaccine administered to healthy adults. Endpoints: Primary endpoint consists of: Local and systemic reactogenicity signs and symptoms during the 7-day period after each vaccination Unsolicited adverse events up to 30 days after each vaccination Serious adverse events through Day 210 Change in log10 antibody response to EBV from baseline to 1 month after the third dose of vaccine (Day 210) as measured by neutralization assay Secondary endpoints: Change in log10 antibody response to EBV gp350 from baseline to Day 210 as measured by luciferase immunoprecipitation system (LIPS) assay Change in log10 CD4 T cell response to EBV gp350 from baseline to Day 210 as measured by intracellular cytokine staining

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
EBV, Epstein-Barr Virus Infection, Infectious Mononucleosis
Keywords
Infectious Mononucleosis, Neutralizing Antibody, CD4+ T cell response, Immune Response

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EBV gp_350 Ferritin Vaccination
Arm Type
Experimental
Arm Description
Adult participants with or without prior EBV infection will receive 3 doses of vaccine
Intervention Type
Biological
Intervention Name(s)
EBV gp350-Ferritin Vaccine
Intervention Description
A 50 micrograms dose of EBV gp350-Ferritin vaccine will be administered intramuscularly for each vaccination at Days 0, 30, and 180 to all participants.
Intervention Type
Other
Intervention Name(s)
Matrix-M1
Intervention Description
Each vaccine dose will consist of 50 micrograms of EBV gp350-Ferritin combined with 49 micrograms of Matrix-M1.
Primary Outcome Measure Information:
Title
Local and systemic reactogenicity; unsolicited adverse events; serious adverse events; change in neutralizing antibody responses to EBV
Description
-Local reactogenicity: pain, tenderness, redness, bruising, swelling; Systemic reactogenicity symptoms: headache, muscle pain, fatigue, chills, oral temperature, joint pain, nausea/ vomiting, diarrhea; Change in log10 antibody response to EBV from baseline to 1 month after third dose of vaccine(Day 210) as measured by neutralization assay.
Time Frame
Reactogenicity during the 7-day period after each dose; unsolicited adverse events up to 30 days after each dose; serious adverse events through 1 month after the third dose:; neutralizing antibody response one month after third dose
Secondary Outcome Measure Information:
Title
Change in antibody responses to EBV gp350; change in CD4+ T cell responses to EBV gp350
Description
-Change in log10 antibody response to EBV from baseline to 1 month after third vaccine dose measured by a luciferase immunoprecipitation assay; --Change in log10 CD4+ T cell response from baseline to one month after third dose measured by an intracellular cytokine staining assay.
Time Frame
Change in antibody responses and change in CD4 T cell responses at 1 month after third dose of vaccine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
29 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 18 to 29 years old Screening procedures and evaluations performed no more than 30 days prior to scheduled administration of the first vaccine dose. Ability of subject to understand and the willingness to sign a written informed consent document. Stated willingness to comply with all study procedures and availability for the duration of the active phase of the study (approximately 18 months) Willingness to allow storage of blood and saliva for future research. In good general health as evidenced by medical history, physical examination, and laboratory screening result. Subject is willing to forgo receipt of a licensed, live vaccine in the 30 days preceding each dose of vaccine or in the 30 days following each dose of vaccine. An FDA-approved inactivated, subunit or replication-defective vaccine (such as COVID-19, influenza, tetanus etc.) and/or a COVID-19 vaccine approved under emergency use authorization can be used >=14 days before or >=14 days after administration of the study vaccine. For females of reproductive potential who are sexually active with a male partner: use of highly effective continuous contraception for at least 30 days prior to Day 0 and agreement to continue use until 60 days after the last dose of vaccine. For males who are sexually active with partners of child-bearing potential: use of highly effective continuous contraception from Day 0 and agreement to continue use until 30 days after the last dose of vaccine. Contraceptive requirements: Because the effects of EBV gp350-Ferritin vaccine on the developing human fetus are unknown, sexually active female participants of childbearing potential must agree to use highly effective contraception as outlined below before study entry and until 60 days after the last dose of vaccine. Females of childbearing potential must have a negative pregnancy test before receiving each dose of the EBV gp350-Ferritin vaccine. During the course of the study, if a participant becomes pregnant or suspects they are pregnant, then they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are: Intrauterine device (IUD) or equivalent Hormonal contraceptive (e.g. consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy prior to dosing). If the participant uses a contraceptive pill, path, or ring, then a barrier method (e.g. male/female condom, cap or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity. A stable, long-term monogamous relationship with a partner who does not pose any potential pregnancy risk, e.g. has undergone a vasectomy at least 6 months prior to the first dose of vaccine or is of the same sex as the participant. A hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy Acceptable forms of contraception for male participants include one of the following: Condom plus spermicide, used before or during sexual intercourse, even if the female partner uses a contraceptive pill, patch, or ring A vasectomy completed at least 6 months before the first dose of vaccine Continuously and completely abstaining from sexual intercourse with a female with child-bearing potential from the first dose of vaccine until 30 days after the last dose. Acceptable contraception for female partners with child-bearing potential of male study participants include one of the following: IUD or equivalent Hormonal contraceptive (e.g. pill, patch, ring, implant or an injection used consistently and that has reached full effect prior to the first dose of vaccine) Hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy Laboratory Criteria within 30 days or less prior to enrollment: Hemoglobin within institutional normal limits or if not, then assessed and deemed not clinically significant by PI or designee White blood cell (WBC) count and differential either within institutional normal reference range or if not then assessed and deemed not clinically significant by PI or designee Total lymphocyte count (lymphocyte absolute) >= 800 cells/mm3 (0.8 K/mcL) Platelet count equal to 125,000 - 500,000/Mm^3 (125-500 K/mcL) Alanine aminotransferase (ALT) <= 1.25x upper limit of normal (ULN) Serum IgG > 600 mg/dL Negative human immunodeficiency virus (HIV) test. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: Women who are breastfeeding or planning to become pregnant while participating through 60 days after the last dose of vaccine Participant has received any of the following: More than 10 days of systemic immunosuppressive medications (>=10 mg prednisone dose or its equivalent) or cytotoxic medication within the 30 days prior to first dose of vaccine or immunomodulating therapy within 180 days prior to first dose of vaccine. Blood products, including immunoglobulin products, within 120 days prior to first dose of vaccine Any live attenuated vaccination within 30 days prior to first dose of vaccine Medically indicated subunit inactivated or replication-defective vaccines, e.g. influenza, pneumococcal, COVID-19 within 14 days of the first dose of vaccine. 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. Participant has any of the following: Febrile illness within 14 days of the first dose of vaccine Obesity, in which any of the following are true: The deltoid muscle cannot be clearly identified Intramuscular (IM) vaccine administration/dosing may be compromised Presence of medical comorbidities such that enrollment is not in the best interests of the participant Serious reactions to vaccines Hereditary, acquired, or idiopathic forms of angioedema Idiopathic urticaria within the past year Asthma that is not well-controlled or required emergent 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 Hypertension that is not well-controlled Thyroid disease that is not well-controlled Bleeding disorder diagnosed by doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) Significant bruising or bleeding difficulties with IM 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kayla D Morgan
Phone
(301) 761-5671
Email
kayla.morgan@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Jessica R Durkee-Shock, M.D.
Phone
(301) 761-6539
Email
jessica.durkee-shock@nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jessica R Durkee-Shock, M.D.
Organizational Affiliation
National Institute of Allergy and Infectious Diseases (NIAID)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone
800-411-1222
Ext
TTY8664111010
Email
prpl@cc.nih.gov

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
.We will return results from CLIA approved testing done in the department of laboratory medicine to participants. Based on results and clinical judgement, we will manage and refer patients appropriately. Non-FDA approved research assay results will not be shared with patients.
IPD Sharing Time Frame
Results from the Clinical Center Laboratory will be available within one to two weeks and will be discussed by the study team.
IPD Sharing Access Criteria
IPD will be shared with the patient. IPD will also be discussed with the study team. If collaborations are initiated the samples will be coded so that the collaborator does not know the names of the patients.
Citations:
PubMed Identifier
22049067
Citation
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.
Results Reference
background
PubMed Identifier
25671130
Citation
Cohen JI. Epstein-barr virus vaccines. Clin Transl Immunology. 2015 Jan 23;4(1):e32. doi: 10.1038/cti.2014.27. eCollection 2015 Jan. Erratum In: Clin Transl Immunology. 2015 Apr;4(4):e36.
Results Reference
background
PubMed Identifier
26279189
Citation
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.
Results Reference
background
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2021-I-0005.html
Description
NIH Clinical Center Detailed Web Page

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Safety and Immunogenicity of an Epstein-Barr Virus (EBV) gp350-Ferritin Nanoparticle Vaccine in Healthy Adults With or Without EBV Infection

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