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

• ClinicalTrials.gov Identifier: NCT04917861
• Recruitment Status: Active, not recruiting
• First Posted: June 8, 2021
• Last Update Posted: September 2, 2022
• Sponsor: ModernaTX, Inc.
• Information provided by (Responsible Party): ModernaTX, Inc.

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 (Clinical Trial)
• Actual Enrollment: 809 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: June 8, 2021
• Estimated Primary Completion Date: April 26, 2024
• Estimated Study Completion Date: April 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 Name: 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 Name: 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 Name: 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 :

1. Number of Solicited Local and Systemic Adverse Reactions (ARs) [ Time Frame: Up to Day 36 (7 days after each vaccination) ]
2. Number Unsolicited Adverse Events (AEs) [ Time Frame: Up to Day 57 (28 days after each vaccination) ]
3. Number of Medically Attended Adverse Events (MAAEs) [ Time Frame: Day 1 throughout the entire study duration (up to Day 700) ]
4. Number of Serious Adverse Events (SAEs) and Adverse Events of Special Interests (AESIs) [ Time Frame: Day 1 throughout the entire study duration (up to Day 700) ]
5. 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) [ Time Frame: Day 57 ]
6. Percentage of Participants With Seroconversion, as Measured by PRNT [ Time Frame: 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 :

1. GMT of ZIKV-Specific nAbs in All Participants, as Measured by PRNT [ Time Frame: Days 1, 8, 29, and 36 ]
2. GMT of ZIKV-Specific nAbs in All Participants, as Measured by Microneutralization (MN) [ Time Frame: Days 1, 8, 29, 36 and 57 ]
3. GMT of ZIKV-Specific nAbs in Initially Flavivirus Seronegative Participants, as Measured by PRNT [ Time Frame: Days 1, 8, 29, and 36 ]
4. GMT of ZIKV-Specific nAbs in Initially Flavivirus Seronegative Participants, as Measured by MN [ Time Frame: Days 1, 8, 29, 36, and 57 ]
5. GMT of ZIKV-Specific nAbs in Initially Flavivirus Seropositive Participants, as Measured by PRNT [ Time Frame: Days 1, 8, 29, and 36 ]
6. GMT of ZIKV-Specific nAbs in Initially Flavivirus Seropositive Participants, as Measured by MN [ Time Frame: Days 1, 8, 29, 36, and 57 ]
7. Geometric Mean Fold Rise (GMFR) of ZIKV-Specific nAbs in All Participants, as Measured by PRNT [ Time Frame: Days 8, 29, 36, and 57 ]
8. GMFR of ZIKV-Specific nAbs in All Participants, as Measured by MN [ Time Frame: Days 8, 29, 36, and 57 ]
9. GMFR of ZIKV-Specific nAbs in Initially Flavivirus Seronegative Participants and Initially Flavivirus Seropositive Participants, as Measured by PRNT [ Time Frame: Days 8, 29, and 36 ]
10. GMFR of ZIKV-Specific nAbs in Initially Flavivirus Seronegative Participants and Initially Flavivirus Seropositive Participants, as Measured by MN [ Time Frame: Days 8, 29, 36, and 57 ]
11. Percentage of Participants With Seroconversion, as Measured by PRNT [ Time Frame: 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).
12. Percentage of Participants With Seroconversion, as Measured by MN [ Time Frame: 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).
13. Percentage of Initially Seronegative Participants With a Seroresponse, as Measured by PRNT [ Time Frame: 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).
14. Percentage of Initially Seronegative Participants With a Seroresponse, as Measured by MN [ Time Frame: 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).
15. 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 [ Time Frame: Days 8, 29, and 36 ]
16. 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 [ Time Frame: Days 8, 29, 36, and 57 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

United States, Iowa

Meridian Clinical Research (Sioux City, IA)

Sioux City, Iowa, United States, 51106

United States, Kansas

Johnson County Clin-Trials

Lenexa, Kansas, United States, 66219

United States, Texas

Benchmark Research - Fort Worth

Fort Worth, Texas, United States, 76135

Puerto Rico

Clinical Research Puerto Rico, Inc.

Guayama, Puerto Rico, 00784

Ponce Medical School Foundation, Inc.

Ponce, Puerto Rico, 00713

Ponce Medical School Foundation, Inc.

Ponce, Puerto Rico, 00716

Clinical Research Puerto Rico, Inc.

San Juan, Puerto Rico, 00909

Latin Clinical Trial Center, Inc.

San Juan, Puerto Rico, 00909

GCM Medical Group, PSC

San Juan, Puerto Rico, 00917

Carribean Medical Research

San Juan, Puerto Rico, 00918

University of Puerto Rico

San Juan, Puerto Rico, 00935

Sponsors and Collaborators

ModernaTX, Inc.

More Information

• Responsible Party: ModernaTX, Inc.
• ClinicalTrials.gov Identifier: NCT04917861
• Other Study ID Numbers: mRNA-1893-P201; HHSO100201600029C ( Other Grant/Funding Number: BARDA )
• First Posted: June 8, 2021
• Last Update Posted: September 2, 2022
• Last Verified: August 2022

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

Keywords provided by ModernaTX, Inc.:

Flavivirus; mRNA-1893; Zika vaccine; Moderna

Additional relevant MeSH terms:

Zika Virus Infection; Arbovirus Infections; Vector Borne Diseases; Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs