A Study of Zika Vaccine mRNA-1893 in Adult Participants Living in Endemic and Non-Endemic Flavivirus Areas

Study Overview
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Brief Summary
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This clinical study will evaluate the safety, tolerability, and reactogenicity of 2 dose levels of messenger RNA (mRNA)-1893 Zika vaccine in comparison to a placebo control in healthy participants who are flavivirus-seronegative and in participants who are flavivirus-seropositive.

Official Title
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A Phase 2, Randomized, Observer-Blind, Placebo-Controlled, Dose Confirmation Study to Evaluate the Safety, Tolerability, and Immunogenicity of Zika Vaccine mRNA-1893 in Adults Aged 18 Through 65 Years and Living in Endemic and Non-Endemic Flavivirus Areas

Conditions
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Zika Virus

Intervention / Treatment
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* Biological: mRNA-1893
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Understands and agrees to comply with the study procedures and provides written informed consent. According to investigator assessment, is in good general health and can comply with study procedures. Female participants of childbearing potential may be enrolled in the study if the participant: has a negative pregnancy test at the Eligibility Visit and on the day of the first investigational product (IP) injection; has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first IP injection; has agreed to continue adequate contraception through 3 months following the last IP injection; and is not currently breastfeeding. Key Exclusion Criteria: Participant is acutely ill or febrile (temperature ≥38.0°Celsius/100.4°Farenheight) on the day of the first or second vaccination. Participant had prior administration of a ZIKV vaccine candidate during a clinical study investigation. Participant had prior administration of a marketed dengue vaccine or dengue vaccine candidate under clinical study investigation. Participant has a body mass index (BMI) from ≤18 or ≥35 kilograms (kg)/square meter (m^2). Participant has a history of myocarditis, pericarditis, or myopericarditis. Participant has a history of a diagnosis or condition that, in the judgement of the investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. Clinically unstable is defined as a diagnosis or condition requiring significant changes in management or medication within the 2 months prior to screening and includes ongoing work-up of an undiagnosed illness that could lead to a new diagnosis or condition. Participant has any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that in the opinion of the investigator, might pose a risk due to participation in the study or could interfere with the interpretation of study results. Participant has as a history of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine, including an mRNA vaccine or any components of an mRNA vaccine. Participant has received or plans to receive a nonstudy vaccine (including authorized or approved vaccines for the prevention of COVID-19) ≤28 days prior to the first IP injection or within 28 days prior to or after any IP injection. Licensed influenza vaccine received within 14 days prior to the first IP injection or plans to receive a licensed influenza vaccine 14 days prior to through 14 days following each IP injection are not exclusionary. Participant has received systemic immunoglobulins or blood products within 3 months prior to the day of enrollment. Participant has donated ≥450 milliliters (mL) of blood products within 28 days of the Day 1 Visit. Participant has participated in an interventional clinical study within 28 days prior to the day of enrollment or plans to do so while enrolled in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1893 Low Dose (2-Dose Regimen)<br>Participants will receive mRNA-1893 at a low dose level administered as a 2-dose regimen with 28-day (-3/+7 days) interval between vaccinations (administered on Day 1 and Day 29). | Biological: mRNA-1893<br>* Solution for injection<br>* Other names: Zika vaccine;|
| Experimental: mRNA-1893 High Dose (2-Dose Regimen)<br>Participants will receive mRNA-1893 at a high dose level administered as a 2-dose regimen with 28-day (-3/+7 days) interval between vaccinations (administered on Day 1 and Day 29). | Biological: mRNA-1893<br>* Solution for injection<br>* Other names: Zika vaccine;|
| Experimental: mRNA-1893 High Dose (1-Dose Regimen)<br>Participants will receive placebo matching to mRNA-1893 on Day 1 and mRNA-1893 at a high dose level administered as a 1-dose regimen (administered on Day 29). There will be 28-day (-3/+7 days) interval between vaccinations. | Biological: mRNA-1893<br>* Solution for injection<br>* Other names: Zika vaccine;Biological: Placebo<br>* 0.9% sodium chloride solution for injection<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo matching to mRNA-1893 administered as a 2-dose regimen with 28-day (-3/+7 days) interval between vaccinations (administered on Day 1 and Day 29). | Biological: Placebo<br>* 0.9% sodium chloride solution for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Solicited Local and Systemic Adverse Reactions (ARs) |  | Up to Day 36 (7 days after each vaccination) | 
| Number Unsolicited Adverse Events (AEs) |  | Up to Day 57 (28 days after each vaccination) | 
| Number of Medically Attended Adverse Events (MAAEs) |  | Day 1 throughout the entire study duration (up to Day 700) | 
| Number of Serious Adverse Events (SAEs) and Adverse Events of Special Interests (AESIs) |  | Day 1 throughout the entire study duration (up to Day 700) | 
| Geometric Mean Titer (GMT) of Zika Virus (ZIKV)-Specific Neutralizing Antibodies (nAb) in All Participants, Initially Flavivirus Seronegative, and Initially Flavivirus Seropositive Participants, as Measured by Plaque Reduction Neutralization Test (PRNT) |  | Day 57 | 
| Percentage of Participants With Seroconversion, as Measured by PRNT | Seroconversion is defined as either an increase in ZIKV-specific nAb titer from below the lower limit of quantification (LLOQ) to a titer equal to or above LLOQ, or an increase of at least 4-fold in ZIKV-specific nAb titer in participants with pre-existing nAb titers (as measured by PRNT). | Day 1 to Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMT of ZIKV-Specific nAbs in All Participants, as Measured by PRNT |  | Days 1, 8, 29, and 36 | 
| GMT of ZIKV-Specific nAbs in All Participants, as Measured by Microneutralization (MN) |  | Days 1, 8, 29, 36 and 57 | 
| GMT of ZIKV-Specific nAbs in Initially Flavivirus Seronegative Participants, as Measured by PRNT |  | Days 1, 8, 29, and 36 | 
| GMT of ZIKV-Specific nAbs in Initially Flavivirus Seronegative Participants, as Measured by MN |  | Days 1, 8, 29, 36, and 57 | 
| GMT of ZIKV-Specific nAbs in Initially Flavivirus Seropositive Participants, as Measured by PRNT |  | Days 1, 8, 29, and 36 | 
| GMT of ZIKV-Specific nAbs in Initially Flavivirus Seropositive Participants, as Measured by MN |  | Days 1, 8, 29, 36, and 57 | 
| Geometric Mean Fold Rise (GMFR) of ZIKV-Specific nAbs in All Participants, as Measured by PRNT |  | Days 8, 29, 36, and 57 | 
| GMFR of ZIKV-Specific nAbs in All Participants, as Measured by MN |  | Days 8, 29, 36, and 57 | 
| GMFR of ZIKV-Specific nAbs in Initially Flavivirus Seronegative Participants and Initially Flavivirus Seropositive Participants, as Measured by PRNT |  | Days 8, 29, and 36 | 
| GMFR of ZIKV-Specific nAbs in Initially Flavivirus Seronegative Participants and Initially Flavivirus Seropositive Participants, as Measured by MN |  | Days 8, 29, 36, and 57 | 
| Percentage of Participants With Seroconversion, as Measured by PRNT | Seroconversion is defined as either an increase in ZIKV-specific nAb titer from below the LLOQ to a titer equal to or above LLOQ, or an increase of at least 4-fold in ZIKV-specific nAb titer in participants with pre-existing nAb titers (as measured by PRNT). | Day 1 to Days 8, 29, and 36 | 
| Percentage of Participants With Seroconversion, as Measured by MN | Seroconversion is defined as either an increase in ZIKV-specific nAb titer from below the LLOQ to a titer equal to or above LLOQ, or an increase of at least 4-fold in ZIKV-specific nAb titer in participants with pre-existing nAb titers (as measured by MN). | Day 1 to Days 8, 29, 36, and 57 | 
| Percentage of Initially Seronegative Participants With a Seroresponse, as Measured by PRNT | Seroresponse is defined as an increase in ZIKV-specific nAb titer (as measured by PRNT) from below the LLOQ to greater than or equal to the LLOQ). | Days 8, 29, and 36 | 
| Percentage of Initially Seronegative Participants With a Seroresponse, as Measured by MN | Seroresponse is defined as an increase in ZIKV-specific nAb titer (as measured by MN) from below the LLOQ to greater than or equal to the LLOQ). | Days 8, 29, 36, and 57 | 
| Percentage of Initially Seropositive Participants With a 2-Fold or 4-Fold Increase in ZIKV-Specific nAb Titers as Compared With Baseline, as Measured by PRNT |  | Days 8, 29, and 36 | 
| Percentage of Initially Seropositive Participants With a 2-Fold or 4-Fold Increase in ZIKV-Specific nAb Titers as Compared With Baseline, as Measured by MN |  | Days 8, 29, 36, and 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Flavivirus, mRNA-1893, Zika vaccine, Moderna