Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults

Background:

Nipah virus (NiV) is transmitted from animals to humans, from humans to humans, and through contaminated food. Infected people may have a cough and trouble breathing. Some people may develop serious symptoms, such as brain inflammation, that can lead to death. There are no drugs or vaccines to treat or prevent NiV infection.

Objective:

To test the safety of an experimental vaccine (mRNA-1215) for NiV. Researchers will also evaluate how participants bodies respond to the vaccine.

Eligibility:

Healthy, nonpregnant adults aged 18 to 60 years.

Design:

Participants will visit the NIH clinic 13 to 15 times over 14 to 16 months.

Participants will get 2 doses of the experimental vaccine during this study at either 1 month or 4 months apart. The vaccine will be given as a shot into the muscle of the upper arm. Participants will stay in the clinic at least 30 minutes after each vaccination.

Participants will be given a diary card and a thermometer. They will record their temperature and any other symptoms for 7 days after each vaccination.

During each follow-up visit, 3 to 14 tubes of blood will be drawn for research.

Participants may undergo an optional procedure called apheresis. A needle will be placed into a vein in each arm. Blood will be removed through one needle. The blood will pass through a machine that separates some of the blood cells. The rest of the blood will return to the body through the other needle.

The study vaccine cannot cause NiV infection.

Design:

This Phase I, dose escalation, open label clinical trial is the first study of mRNA-1215 in healthy adults to evaluate the safety, tolerability, and immunogenicity of a Nipah virus (NiV) mRNA vaccine. The hypotheses are that the vaccine will be safe, tolerable, and will elicit an immune response in healthy adults.

Study Product:

mRNA-1215 is a novel mRNA vaccine that encodes for the secreted prefusion stabilized F component covalently linked to G monomer (pre-F/G) of Malaysian strain NiV, resulting in a post-expression trimerization. mRNA-1215 was co-developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Disease (NIAID) and ModernaTX, Inc, and manufactured by ModernaTX.

Subjects:

Healthy adults, 18 to 60 years of age.

Plan:

Subjects will be enrolled at the NIH Clinical Center and will receive mRNA-1215 via intramuscular (IM) injection by needle and syringe into the deltoid muscle. A dose escalation safety evaluation will occur to ensure the safety data support proceeding to the higher dose group. The mRNA-1215 vaccine dose for Group 4 will be selected based on interim analysis of safety and immunogenicity data from Groups 1-3. Subjects will be evaluated for safety and immune responses through clinical observation and blood collection at specified timepoints throughout the study. The study schema is as follows:

Study Schema

Group Subjects Dose/Route Day 0 Week 4

1. 10 25 mcg IM X X
2. 10 50 mcg IM X X
3. 10 100 mcg IM X X
4. 10 10 mcg IM X X

Total \*\*40

\*\*Enrollment up to 50 subjects is permitted in case additional evaluations are required for safety or immunogenicity.

Duration:

Subjects will be evaluated for safety and immune responses throughout the study for 52 weeks following last product administration.

Eligibility Criteria:
* INCLUSION CRITERIA:

A subject must meet all of the following criteria:

1. Healthy adults between the ages of 18-60 years inclusive.
2. Based on history and physical examination, in good general health and without history of any of the conditions listed in the exclusion criteria.
3. Able and willing to complete the informed consent process.
4. Available for clinic visits for 52 weeks after last product administration.
5. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
6. Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) of 18 to 35 within the 56 days before enrollment.

   Laboratory Criteria within 56 days before enrollment:
7. White blood cells (WBC) and differential within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval.
8. Total lymphocyte count \>= 800 cells/microL.
9. Platelets = 125,000 - 500,000 cells/microL.
10. Hemoglobin within institutional normal range or accompanied by the PI or designee approval.
11. Alanine aminotransferase (ALT) \<= 1.25 X institutional upper limit of normal (ULN).
12. Aspartate aminotransferase (AST) \<= 1.25 X institutional ULN.
13. Alkaline phosphatase (ALP) \<1.1 X institutional ULN.
14. Total bilirubin within institutional normal range or accompanied by the PI or designee approval.
15. Serum creatinine \<= 1.1 X institutional ULN.
16. Negative for HIV infection by an FDA-approved method of detection

    Criteria applicable to women of childbearing potential:
17. Negative beta-human chorionic gonadotropin (Beta-HCG) pregnancy test (urine or serum) on the day of enrollment.
18. Agrees to use an effective means of birth control from at least 21 days prior to enrollment through the end of the study.

EXCLUSION CRITERIA:

A subject will be excluded if one or more of the following conditions apply:

1. Breast-feeding or planning to become pregnant during the study.
2. More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment.
3. Blood products within 16 weeks prior to enrollment.
4. Any vaccine, including COVID-19 vaccines, received within 4 weeks prior to enrollment.
5. Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study
6. Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule.
7. Current anti-TB prophylaxis or therapy.
8. Known immediate hypersensitivity to any component of the study product, including polyethylene glycol (PEG).
9. Confirmed past NiV infection, prior residence in (\>6 months), or planned travel for any length of time during the study to countries where NiV infection is endemic, eg. Bangladesh, India, Philippines.

   Subject has a history of any of the following clinically significant conditions:
10. Serious reactions to vaccines that preclude receipt of the study vaccination, including allergic reaction (anaphylaxis, urticaria or allergic reaction requiring medical intervention) to SARS-CoV-2 mRNA vaccines, as determined by the investigator
11. History of myocarditis and/or pericarditis
12. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
13. Asthma that is not well controlled
14. Diabetes mellitus (type I or II), with the exception of gestational diabetes
15. Thyroid disease that is not well controlled
16. Idiopathic urticaria within the past year
17. Autoimmune disease or immunodeficiency
18. Hypertension that is not well controlled
19. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws
20. Malignancy that is active or history of malignancy that is likely to recur during the period of the study
21. Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years.
22. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
23. Guillain-Barre Syndrome
24. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a subject s ability to give informed consent, including but not limited to clinically significant forms of: infectious diseases, drug or alcohol abuse, autoimmune diseases, psychiatric disorders, or heart disease.