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

• ClinicalTrials.gov Identifier: NCT05398796
• Recruitment Status: Active, not recruiting
• First Posted: June 1, 2022
• Last Update Posted: April 26, 2024
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Moderna TX, Inc
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information

• First Submitted Date: May 27, 2022
• First Posted Date: June 1, 2022
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: July 11, 2022
• Estimated Primary Completion Date: October 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2022)

• To evaluate the safety and tolerability of a 2-dose vaccine regimen of mRNA-1215 [ Time Frame: Through 52 weeks after last product administration ]
  X mcg IM of mRNA-1215 to healthy adults; dose will be determined based on evaluation of Groups 1-3.
• To evaluate the safety and tolerability of a 2-dose vaccine regimen of mRNA-1215 [ Time Frame: Through 52 weeks after last product administration ]
  50 mcg IM of mRNA-1215 to healthy adults
• To evaluate the safety and tolerability of a 2-dose vaccine regimen of mRNA-1215 [ Time Frame: Through 52 weeks after last product administration ]
  25 mcg IM of mRNA-1215 to healthy adults
• To evaluate the safety and tolerability of a 2-dose vaccine regimen of mRNA-1215 [ Time Frame: Through 52 weeks after last product administration ]
  100 mcg IM of mRNA-1215 to healthy adults

Original Primary Outcome Measures (submitted: May 31, 2022)

• To evaluate the safety and tolerability of a 2-dose vaccine regimen of mRNA-1215 [ Time Frame: Through 52 weeks after last product administration ]
  100 mcg IM of mRNA-1215 to healthy adults
• To evaluate the safety and tolerability of a 2-dose vaccine regimen of mRNA-1215 [ Time Frame: Through 52 weeks after last product administration ]
  X mcg IM of mRNA-1215 to healthy adults; dose will be determined based on evaluation of Groups 1-3.
• To evaluate the safety and tolerability of a 2-dose vaccine regimen of mRNA-1215 [ Time Frame: Through 52 weeks after last product administration ]
  25 mcg IM of mRNA-1215 to healthy adults
• To evaluate the safety and tolerability of a 2-dose vaccine regimen of mRNA-1215 [ Time Frame: Through 52 weeks after last product administration ]
  50 mcg IM of mRNA-1215 to healthy adults

Current Secondary Outcome Measures (submitted: May 31, 2022)

To evaluate antibody responses to the mRNA-1215 vaccine [ Time Frame: 2 weeks after last product administration ]

The antibody responses to mRNA-1215 will be evaluated at each dose level.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults
• Official Title: VRC 322/DMID 21-0016: A Phase I, Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults

Brief Summary

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.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Nipah Virus Infection

Intervention

Biological: mRNA -1215

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.

Study Arms

• Experimental: Group 1
  25 mcg IM
  Intervention: Biological: mRNA -1215
• Experimental: Group 2
  50 mcg IM
  Intervention: Biological: mRNA -1215
• Experimental: Group 3
  100 mcg IM
  Intervention: Biological: mRNA -1215
• Experimental: Group 4
  Intervention: Biological: mRNA -1215

Publications *

• Zelnik N, Leshinsky E, Kolodny EH. Familial spastic paraparesis. Is it a mitochondrial disorder? Pediatr Neurosurg. 1995;23(4):225-6. doi: 10.1159/000120963. No abstract available.
• Loomis RJ, Stewart-Jones GBE, Tsybovsky Y, Caringal RT, Morabito KM, McLellan JS, Chamberlain AL, Nugent ST, Hutchinson GB, Kueltzo LA, Mascola JR, Graham BS. Structure-Based Design of Nipah Virus Vaccines: A Generalizable Approach to Paramyxovirus Immunogen Development. Front Immunol. 2020 Jun 11;11:842. doi: 10.3389/fimmu.2020.00842. eCollection 2020.
• Loomis RJ, DiPiazza AT, Falcone S, Ruckwardt TJ, Morabito KM, Abiona OM, Chang LA, Caringal RT, Presnyak V, Narayanan E, Tsybovsky Y, Nair D, Hutchinson GB, Stewart-Jones GBE, Kueltzo LA, Himansu S, Mascola JR, Carfi A, Graham BS. Chimeric Fusion (F) and Attachment (G) Glycoprotein Antigen Delivery by mRNA as a Candidate Nipah Vaccine. Front Immunol. 2021 Dec 8;12:772864. doi: 10.3389/fimmu.2021.772864. eCollection 2021.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 31, 2022): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 1, 2024
• Estimated Primary Completion Date: October 1, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05398796
• Other Study ID Numbers: 10000687; 000687-I
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: .Only aggregate data will be shared.

• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Same as current
• Collaborators: Moderna TX, Inc

Investigators

• Principal Investigator: Lesia K Dropulic, M.D.; National Institute of Allergy and Infectious Diseases (NIAID)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: April 24, 2024