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

Sponsor

ModernaTX, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04917861

Collaborator

(none)

800

Enrollment

Locations

Arms

34.6

Anticipated Duration (Months)

72.7

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Zika Virus	Biological: mRNA-1893 Biological: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 8, 2021

Anticipated Primary Completion Date :

Apr 26, 2024

Anticipated Study Completion Date :

Apr 26, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mRNA-1893 Low Dose (2-Dose Regimen) 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 Solution for injection Other Names: Zika vaccine
Experimental: mRNA-1893 High Dose (2-Dose Regimen) 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 Solution for injection Other Names: Zika vaccine
Experimental: mRNA-1893 High Dose (1-Dose Regimen) 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 Solution for injection Other Names: Zika vaccine Biological: Placebo 0.9% sodium chloride solution for injection
Placebo Comparator: Placebo 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 0.9% sodium chloride solution for injection

Outcome Measures

Primary Outcome Measures

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 [Day 1 to Day 57]
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).

Secondary Outcome Measures

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 [Day 1 to Days 8, 29, and 36]
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).
Percentage of Participants With Seroconversion, as Measured by MN [Day 1 to Days 8, 29, 36, and 57]
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).
Percentage of Initially Seronegative Participants With a Seroresponse, as Measured by PRNT [Days 8, 29, and 36]
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).
Percentage of Initially Seronegative Participants With a Seroresponse, as Measured by MN [Days 8, 29, 36, and 57]
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).
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Meridian Clinical Research (Sioux City, IA)	Sioux City	Iowa	United States	51106
2	Johnson County Clin-Trials	Lenexa	Kansas	United States	66219
3	Benchmark Research - Fort Worth	Fort Worth	Texas	United States	76135
4	Clinical Research Puerto Rico, Inc.	Guayama		Puerto Rico	00784
5	Ponce Medical School Foundation, Inc.	Ponce		Puerto Rico	00713
6	Ponce Medical School Foundation, Inc.	Ponce		Puerto Rico	00716
7	Clinical Research Puerto Rico, Inc.	San Juan		Puerto Rico	00909
8	Latin Clinical Trial Center, Inc.	San Juan		Puerto Rico	00909
9	GCM Medical Group, PSC	San Juan		Puerto Rico	00917
10	Carribean Medical Research	San Juan		Puerto Rico	00918
11	University of Puerto Rico	San Juan		Puerto Rico	00935