mRNA EBV Vaccine for EBV Infection

Recruiting at 47 trial locations

Overseen By Moderna WeCare Team

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: ModernaTX, Inc.

Must not be taking: Immunosuppressants, Immune-modifying drugs

Disqualifiers: Acute illness, Chronic illness, Myocarditis, others

Compensation: Varies

Number of Visits: 6

474 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety of a new vaccine called mRNA-1195 in healthy adults. The study is split into two parts based on whether participants have been exposed to Epstein-Barr Virus. The vaccine works by teaching the body to recognize and fight the virus.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressants or immune-modifying drugs, you may not be eligible. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the mRNA-1195 treatment for EBV infection?

Research shows that mRNA-based vaccines targeting specific parts of the Epstein-Barr virus (EBV) can activate the immune system effectively in mice, helping to slow down tumor growth and improve survival. This suggests that similar mRNA treatments, like mRNA-1195, might also be effective against EBV-related conditions. ^{1 2 3 4 5}

What safety data exists for the mRNA EBV vaccine or similar EBV vaccines in humans?

The safety of a recombinant gp350 EBV vaccine was evaluated in healthy adults, showing a good safety profile with most symptoms being mild and within acceptable ranges, although one serious adverse event was reported. However, no specific safety data for the mRNA EBV vaccine (mRNA-1195) is available from the provided research. ^{2 6 7 8 9}

What makes the mRNA-1195 vaccine unique for treating EBV infection?

The mRNA-1195 vaccine is unique because it uses mRNA technology to target specific parts of the Epstein-Barr virus (EBV) proteins that are rich in T-cell epitopes, which helps the immune system recognize and fight the virus more effectively. This approach is different from traditional vaccines as it focuses on activating both cellular and humoral immunity, potentially offering a new treatment option for EBV-associated cancers. ^{1 10 11 12 13}

Eligibility Criteria

This trial is for healthy adults aged 18-55 who either have been exposed to EBV (Part A) or not (Part B). Participants must be in good health, able to follow the study plan, and if female and able to become pregnant, they must use effective birth control. People with recent fevers, unstable chronic illnesses, drug/alcohol abuse history, or those on certain immune-altering drugs can't join.

Inclusion Criteria

For Part A: Positive EBV serostatus at Screening

For Part B: Negative EBV serostatus at Screening

Is in good general health and can comply with study procedures

Exclusion Criteria

Participant is acutely ill or febrile (temperature ≥38.0 degrees Celsius [°C]/100.4 degrees Fahrenheit [°F]) 72 hours prior to or at the Screening Visit or Day 1

My chronic illness is stable and hasn't required new treatments in the last 2 months.

Any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive 3 IM injections of either mRNA-1189, mRNA-1195.1, or mRNA-1195.2 at various dose levels on Days 1, 57, and 169

24 weeks

3 visits (in-person)

Treatment Part B

Participants receive 3 IM injections of mRNA-1195 at low, middle, or high dose levels on Days 1, 57, and 169

24 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• mRNA-1195

Trial Overview The study tests the safety of an Epstein-Barr Virus vaccine called mRNA-1195 in two forms (mRNA-1195.1 and mRNA-1195.2), comparing it against another candidate vaccine mRNA-1189 and a placebo. The goal is to see how participants' bodies react to these vaccines.

Participant Groups

Group I: Part B: mRNA-1195 Middle Dose Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195 (at a dose level selected based on the Part A interim analysis) middle dose on Days 1, 57, and 169.

Group II: Part B: mRNA-1195 Low Dose Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195 (at a dose level selected based on the Part A interim analysis) low dose on Days 1, 57, and 169.

Group III: Part B: mRNA-1195 High Dose Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195 (at a dose level selected based on the Part A interim analysis) high dose on Days 1, 57, and 169.

Group IV: Part A: mRNA-1195.2 Dose Level 4 Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195.2 at Dose Level 4 on Days 1, 57, and 169.

Group V: Part A: mRNA-1195.2 Dose Level 3 Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195.2 at Dose Level 3 on Days 1, 57, and 169.

Group VI: Part A: mRNA-1195.2 Dose Level 2 Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195.2 at Dose Level 2 on Days 1, 57, and 169.

Group VII: Part A: mRNA-1195.2 Dose Level 1 Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195.2 at Dose Level 1 on Days 1, 57, and 169.

Group VIII: Part A: mRNA-1195.1 Dose Level 4 Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195.1 at Dose Level 4 on Days 1, 57, and 169.

Group IX: Part A: mRNA-1195.1 Dose Level 3 Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195.1 at Dose Level 3 on Days 1, 57, and 169.

Group X: Part A: mRNA-1195.1 Dose Level 2 Experimental Treatment 1 Intervention

Participants will receive 3 IM injections of mRNA-1195.1 at Dose Level 2 on Days 1, 57, and 169.

Group XI: Part A: mRNA-1195.1 Dose Level 1 Experimental Treatment 1 Intervention

Participants will receive 3 intramuscular (IM) injections of mRNA-1195.1 at Dose Level 1 on Days 1, 57, and 169.

Group XII: Part A: mRNA-1189 Active Control 1 Intervention

Participants will receive 3 IM injections of mRNA-1189 on Days 1, 57, and 169.

Group XIII: Part A: Placebo Placebo Group 1 Intervention

Participants will receive 3 IM injections of study drug-matching placebo on Days 1, 57, and 169.

Group XIV: Part B: Placebo Placebo Group 1 Intervention

Participants will receive 3 IM injections of study drug-matching placebo on Days 1, 57, and 169.

Who Is Running the Clinical Trial?

ModernaTX, Inc.

Lead Sponsor

Trials

127

Recruited

66,790,000+

Dr. Stephen Hoge

ModernaTX, Inc.

Chief Medical Officer

MD from Harvard Medical School

Stéphane Bancel

ModernaTX, Inc.

Chief Executive Officer since 2011

MBA from Harvard Business School, MSc in Engineering from École Centrale Paris

Findings from Research

In a study of 510 university students, penetrative sexual intercourse was identified as a significant risk factor for acquiring Epstein-Barr virus (EBV), with 46% of initially EBV-seronegative students seroconverting over three years, and 25% of those developing infectious mononucleosis (IM).

EBV type 1 was found to be more likely associated with IM compared to silent seroconversion, suggesting that a vaccine targeting EBV could potentially prevent IM by reducing viral load rather than requiring complete immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cohort study among university students: identification of risk factors for Epstein-Barr virus seroconversion and infectious mononucleosis. Crawford, DH., Macsween, KF., Higgins, CD., et al.[2022]

The recombinant subunit gp350 Epstein-Barr virus (EBV) vaccine was tested in 148 healthy adult volunteers and demonstrated a good safety profile, with most side effects being mild and acceptable, although one serious adverse event was reported.

The vaccine formulations were effective in generating immune responses, specifically inducing gp350-specific antibodies, including neutralizing antibodies, indicating potential efficacy in protecting against EBV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults. Moutschen, M., Léonard, P., Sokal, EM., et al.[2007]

A study involving 1217 females with suspected adverse events after HPV vaccination found that EBV infection around the time of vaccination is not a significant risk factor for these events, as only a small number had recent EBV infections.

The higher rates of EBV testing among those reporting adverse events suggest that the symptoms attributed to the vaccine may actually be due to other factors, rather than a direct link to the HPV vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are unexplained adverse health events following HPV vaccination associated with infectious mononucleosis? - A Danish nationwide matched case-control study. Krogsgaard, LW., Helmuth, IG., Bech, BH., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

mRNA-based Vaccines Targeting the T-cell Epitope-rich Domain of Epstein Barr Virus Latent Proteins Elicit Robust Anti-Tumor Immunity in Mice. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Designing an effective vaccine to prevent Epstein-Barr virus-associated diseases: challenges and opportunities. [2022]

3. England pubmed.ncbi.nlm.nih.gov

LMP2-mRNA lipid nanoparticle sensitizes EBV-related tumors to anti-PD-1 therapy by reversing T cell exhaustion. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Four Decades of Prophylactic EBV Vaccine Research: A Systematic Review and Historical Perspective. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Prophylactic and therapeutic strategies for Epstein-Barr virus-associated diseases: emerging strategies for clinical development. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

A cohort study among university students: identification of risk factors for Epstein-Barr virus seroconversion and infectious mononucleosis. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults. [2007]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Progress, prospects, and problems in Epstein-Barr virus vaccine development. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Are unexplained adverse health events following HPV vaccination associated with infectious mononucleosis? - A Danish nationwide matched case-control study. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Mapping of the gene coding for Epstein-Barr virus-determined nuclear antigen EBNA3 and its transient overexpression in a human cell line by using an adenovirus expression vector. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Therapeutic vaccination against the rhesus lymphocryptovirus EBNA-1 homologue, rhEBNA-1, elicits T cell responses to novel epitopes in rhesus macaques. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Epstein-Barr-virus-infected human T-cell line with a unique pattern of viral-gene expression. [2019]

13. China pubmed.ncbi.nlm.nih.gov

[Functional effects of dendritic cells transfected with Epstein-Barr virus latent membrane protein 2A recombinant adenovirus]. [2006]