Dose Escalation, Open-Label Clinical Trial to Evaluate Safety, Tolerability and Immunogenicity of a Nipah Virus (NiV) mRNA Vaccine, mRNA-1215, in Healthy Adults
- Conditions
- Nipah Virus Infection
- Interventions
- Biological: mRNA -1215
- Registration Number
- NCT05398796
- 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 infection and 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 visited the NIH clinic 13 to 15 times over 14 to 16 months.
Participants received 2 doses of the experimental vaccine at 1 month apart. The vaccine was given as a shot into the muscle of the upper arm. Participants stayed in the clinic at least 30 minutes after each vaccination.
Participants were given a diary card and a thermometer. They recorded their temperature and any other reactogenicity symptoms for 7 days after each vaccination.
During each follow-up visit, 3 to 14 tubes of blood were drawn for research.
Some participants underwent an optional procedure called apheresis. A needle is placed into a vein in each arm. Blood is removed through one needle. The blood passed through a machine that separates some of the blood cells. The rest of the blood is returned to the body through another needle.
The mRNA-1215 vaccine cannot cause NiV infection.
- Detailed Description
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
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 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Group 1 mRNA -1215 25 mcg IM, 2 injections 4 weeks apart Group 2 mRNA -1215 50 mcg IM, 2 injections 4 weeks apart Group 4 mRNA -1215 10 mcg IM, 2 injections 4 weeks apart Group 3 mRNA -1215 100 mcg IM, 2 injections 4 weeks apart
- Primary Outcome Measures
Name Time Method Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration 7 days after product administration Participants recorded the occurrence of solicited local symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Product Administration 7 days after product administration Participants recorded the occurrence of solicited systemic symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007.
Number of Participants With Serious Adverse Events Following Product Administration Day 0 after product administration through Day 392, up to Week 56 SAEs were recorded from receipt of product administration through the last study visit at Week 56. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration Day 0 through 28 days post product administration, up to Week 4 Unsolicited AEs and attribution assessments were recorded in the study database from receipt of study product administration through the visit scheduled for 4 weeks after study product administration. At other time periods greater than 4 weeks after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With New Chronic Medical Conditions Following Product Administration Day 0 after product administration through Day 392, up to Week 56 New chronic medical conditions that required ongoing medical management were recorded from receipt of study product administration through the last expected study visit through Day 392, up to Week 56. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity
Number of Participants With Adverse Events of Special Interest (AESI) Following Product Administration Day 0 after product administration through Day 392, up to Week 56 An AESI is an AE (serious or nonserious) of scientific medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the investigator to the Sponsor is required.
Number of Participants With Medically Attended Adverse Events (MAAEs) Following Product Administration First vaccination to 6 months MAAEs are defined as adverse events leading to hospitalization, an emergency room visit or an otherwise unscheduled visit to or from medical personnel, for any reason.
Number of Participants With Abnormal Laboratory Measures of Safety Following Product Administration Day 0 after product administration through Day 392, up to Week 56 Abnormal lab results recorded as unsolicited adverse events (AEs) are summarized\*. Safety lab parameters included pregnancy test, hematology and chemistry labs, and HIV Serology diagnostic test. Institutional lab normal ranges as well as Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.
- Secondary Outcome Measures
Name Time Method Geometric Mean NiV(M) Pre-F Binding Antibody Titer (GMTs) and 95% Confidence Intervals (CIs). Serum samples collected at baseline (Week 0) and at two weeks after the second product administration (Week 6). Vaccine-induced binding antibody titers against Pre-F antigen of Nipah virus Malaysia strain (NiV(M)) were measured by ELISA. The value of the antibody response was determined by obtaining half of the maximum effective concentration (EC50) titer from the optical density 450 nm curves for the function of the reciprocal dilution using a four-parameter logistic curve fit in Prism (version 10.2.2). NiV Pre-F EC50 titers were normalized using the World Health Organization (WHO)/National Institute for Biological Standards and Control (NIBSC) international standard (IS, NIBSC code 22/130) and are reported as group geometric mean titers (GMTs) and 95% confidence intervals (CIs) in international units per milliliter (IU/ml).
Geometric Mean NiV(M) G Binding Antibody Titer (GMTs) and 95% Confidence Intervals (CIs). Serum samples collected at baseline (Week 0) and at two weeks after the second product administration (Week 6). Vaccine-induced binding antibody titers against G antigen of Nipah virus Malaysia strain (NiV(M)) were measured by ELISA. The value of the antibody response was determined by obtaining half of the maximum effective concentration (EC50) titer from the optical density 450 nm curves for the function of the reciprocal dilution using a four-parameter logistic curve fit in Prism (version 10.2.2). NiV G EC50 titers were normalized using the World Health Organization (WHO)/National Institute for Biological Standards and Control (NIBSC) international standard (IS, NIBSC code 22/130) and are reported as group geometric mean titers (GMTs) and 95% confidence intervals (CIs) in international units per milliliter (IU/ml).
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
National Institutes of Health Clinical Center🇺🇸Bethesda, Maryland, United States