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

Design:

This Phase I, dose escalation, open label clinical trial was 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 were that the vaccine would be safe, tolerable, and would elicit an immune response in healthy adults.

Study Product:

The investigational mRNA-1215 vaccine is a lipid nanoparticle dispersion containing mRNA that encodes for a secreted prefusion stabilized F component covalently linked to a G monomer (PreF/G) of a NiV Malaysian 1999 strain with a trimerization domain resulting in secretion of a trimer of heterodimers.

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.

Participants:

Healthy adults, 18 to 60 years of age.

Plan:

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

Study Schema

Group Participants Dose/Route Day 0 Week 4

• 10 25 mcg IM X X
• 10 50 mcg IM X X
• 10 100 mcg IM X X
• 10 10 mcg IM X X

Total **40

**Enrollment of up to 50 subjects was permitted in case additional evaluations were required for safety or immunogenicity.

Duration:

Participants were evaluated for safety and immune responses throughout the study for 52 weeks following the second vaccine dose.

• INCLUSION CRITERIA:

A volunteer must meet all of the following criteria:

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

Laboratory Criteria within 56 days before enrollment:

• White blood cells (WBC) and differential within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval.
• Total lymphocyte count >= 800 cells/microL.
• Platelets = 125,000 - 500,000 cells/microL.
• Hemoglobin within institutional normal range or accompanied by the PI or designee approval.
• Alanine aminotransferase (ALT) <= 1.25 X institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST) <= 1.25 X institutional ULN.
• Alkaline phosphatase (ALP) <1.1 X institutional ULN.
• Total bilirubin within institutional normal range or accompanied by the PI or designee approval.
• Serum creatinine <= 1.1 X institutional ULN.
• Negative for HIV infection by an FDA-approved method of detection

Criteria applicable to women of childbearing potential:

• Negative beta-human chorionic gonadotropin (Beta-HCG) pregnancy test (urine or serum) on the day of enrollment.
• 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 volunteer will be excluded if one or more of the following conditions apply:

• Breast-feeding or planning to become pregnant during the study.
• 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.
• Blood products within 16 weeks prior to enrollment.
• Any vaccine, including COVID-19 vaccines, received within 4 weeks prior to enrollment.
• Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study
• Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule.
• Current anti-TB prophylaxis or therapy.
• Known immediate hypersensitivity to any component of the study product, including polyethylene glycol (PEG).
• 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.

Volunteer has a history of any of the following clinically significant conditions:

• 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
• History of myocarditis and/or pericarditis
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
• Asthma that is not well controlled
• Diabetes mellitus (type I or II), with the exception of gestational diabetes
• Thyroid disease that is not well controlled
• Idiopathic urticaria within the past year
• Autoimmune disease or immunodeficiency
• Hypertension that is not well controlled
• 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
• Malignancy that is active or history of malignancy that is likely to recur during the period of the study
• 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.
• Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
• Guillain-Barre Syndrome
• 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.