Safety, Tolerability, and Immunogenicity of Zika Vaccine mRNA-1893 in Healthy Flavivirus Seropositive and Seronegative Adults

• ClinicalTrials.gov Identifier: NCT04064905
• Recruitment Status: Completed
• First Posted: August 22, 2019
• Last Update Posted: April 22, 2021
• Sponsor: ModernaTX, Inc.
• Collaborator: Biomedical Advanced Research and Development Authority
• Information provided by (Responsible Party): ModernaTX, Inc.

Tracking Information

• First Submitted Date: August 20, 2019
• First Posted Date: August 22, 2019
• Last Update Posted Date: April 22, 2021
• Actual Study Start Date: July 30, 2019
• Actual Primary Completion Date: March 22, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 21, 2019)

• Frequency and grade of each solicited local and systemic reactogenicity adverse event (AE) [ Time Frame: 7-day follow-up period after each vaccination ]
• Frequency and grade of any unsolicited AEs [ Time Frame: 28-day follow-up period after each vaccination ]
• Frequency of any medically attended adverse event (MAAE), serious adverse event (SAE), and adverse event of special interest (AESI) [ Time Frame: Day 1 to the end of study (EOS) Visit at Month 13 ]

Original Primary Outcome Measures (submitted: August 20, 2019)

• Frequency and grade of each solicited local and systemic reactogenicity AE [ Time Frame: 7-day follow-up period after each vaccination ]
• Frequency and grade of any unsolicited AEs [ Time Frame: 28-day follow-up period after each vaccination ]
• Frequency of any MAAE, SAE, and AESI [ Time Frame: Day 1 to the EOS Visit at Month 13 ]

Current Secondary Outcome Measures (submitted: August 21, 2019)

• Geometric mean titer (GMT) of serum neutralizing antibodies (nAb) against zika virus (ZIKV) as measured by Plaque Reduction Neutralization Test (PRNT) [ Time Frame: Day 1, Day 29, Day 57, Month 7, and Month 13 ]
• GMT of nAb in initially seronegative participants against ZIKV as measured by PRNT [ Time Frame: Day 1, Day 29, Day 57, Month 7, and Month 13 ]
• GMT of nAb in initially seropositive participants against ZIKV as measured by PRNT [ Time Frame: Day 1, Day 29, Day 57, Month 7, and Month 13 ]
• Percentage of participants who seroconverted [ Time Frame: Day 1 (baseline) to Day 29, from Day 1 to Day 57, from Day 1 to Month 7, and from Day 1 to Month 13 ]
  A seroconversion is defined as a change of PRNT from below the LOQ to a PRNT equal to or above 1:10, or a multiplication by at least 4 in subjects with pre-existing PRNT titers
• Proportion of initially seronegative participants with a seroresponse as measured by PRNT [ Time Frame: Day 29, Day 57, Month 7, and Month 13 ]
• Proportion of initially seropositive participants with a 2-fold or 4-fold increase in nAb titers as compared with baseline as measured by PRNT [ Time Frame: Day 29, Day 57, Month 7, and Month 13 ]

Original Secondary Outcome Measures (submitted: August 20, 2019)

• GMT of nAb against ZIKV as measured by PRNT [ Time Frame: Day 1, Day 29, Day 57, Month 7, and Month 13 ]
• GMT of nAb in initially seronegative participants against ZIKV as measured by PRNT [ Time Frame: Day 1, Day 29, Day 57, Month 7, and Month 13 ]
• GMT of nAb in initially seropositive participants against ZIKV as measured by PRNT [ Time Frame: Day 1, Day 29, Day 57, Month 7, and Month 13 ]
• Percentage of participants who seroconverted [ Time Frame: Day 1 (baseline) to Day 29, from Day 1 to Day 57, from Day 1 to Month 7, and from Day 1 to Month 13 ]
  A seroconversion is defined as a change of PRNT from below the LOQ to a PRNT equal to or above 1:10, or a multiplication by at least 4 in subjects with pre-existing PRNT titers
• Proportion of initially seronegative participants with a seroresponse as measured by PRNT [ Time Frame: Day 29, Day 57, Month 7, and Month 13 ]
• Proportion of initially seropositive participants with a 2-fold or 4-fold increase in nAb titers as compared with baseline as measured by PRNT [ Time Frame: Day 29, Day 57, Month 7, and Month 13 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Immunogenicity of Zika Vaccine mRNA-1893 in Healthy Flavivirus Seropositive and Seronegative Adults
• Official Title: A Phase 1, Randomized, Observer-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Tolerability, and Immunogenicity of Zika Vaccine mRNA-1893 in Healthy Flavivirus Seropositive and Seronegative Adults
• Brief Summary: This clinical study will evaluate the safety, tolerability and reactogenicity of mRNA-1893 Zika vaccines in flavivirus seronegative and flavivirus seropositive participants
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Observer blind

Primary Purpose: Prevention

• Condition: Zika Virus

Intervention

• Biological: mRNA-1893
  Zika vaccine
• Other: Placebo
  0.9% sodium chloride

Study Arms

• Experimental: mRNA-1893
  Intervention: Biological: mRNA-1893
• Placebo Comparator: Placebo
  0.9% sodium chloride
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 20, 2019): 120
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: March 22, 2021
• Actual Primary Completion Date: March 22, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Agrees to comply with the study procedures and provides written informed consent
• 18 to 49 years of age
• In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., complete diary cards, return for follow-up visits, be available for safety telephone calls).
• Is in good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, and physical examination at screening.
• Negative urine pregnancy test at the Screening visit and at the day of each vaccination for females of childbearing potential.
• Male participants must agree to practice adequate contraception from the time of the first vaccination and through 3 months following the last vaccination.
• For flavivirus-seropositive group, has positive flavivirus test results (including dengue, West Nile, and Zika) as determined by ELISA or other commercially available serological assay.
• For flavivirus-seronegative group, has negative flavivirus test results (including dengue, West Nile, and Zika) as determined by ELISA or other commercially available serological assay.

Exclusion Criteria:

• Has any acute or chronic, Clinically Significant disease in the opinion of the investigator.
• Has received a vaccine for dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, Yellow Fever, or Zika.
• Has a neurologic disorder
• Has a body mass index that is ≤ 18 or ≥ 35 kg/m2.
• Has elevated liver function tests
• Has clinical laboratory test results (hematology, serum chemistry, or coagulation) with a toxicity score of Grade ≥ 1 at Screening.
• Has a bleeding disorder that would contraindicate IM injections or phlebotomy.
• Reports a diagnosis of congenital or acquired immunodeficiency (including HIV infection), or autoimmune disease.
• Has a history of hypersensitivity or severe reactions to previous vaccinations or any component of the study vaccine.
• Has a history of idiopathic urticaria.
• Reports a previous diagnosis of hematologic malignancy or pre-malignancy or a diagnosis of any other malignancy within the previous 10 years (excluding nonmelanoma skin cancer).
• Has a medical, psychiatric, or occupational condition that, in the opinion of the investigator, might pose an additional risk to the participant due to participation in the study or would interfere with the evaluation of the study vaccines or the interpretation of study results.
• Is acutely ill or febrile on the day of screening (Day 0) or randomization (Day 1).
• Has a history of inflammatory arthritis.
• Has a history of febrile disease with arthritis or arthralgia within 2 weeks of administration of any study vaccine.
• Has received an investigational or nonregistered product (drug or vaccine) within 30 days before the first dose of study vaccine or has plans for administration during the study period.
• Has received or is scheduled to receive an inactivated vaccine within the period from 14 days before, or through 14 days after, administration of any study vaccination.
• Has received or is scheduled to receive a live virus vaccine administered within the period from 28 days before, or through 28 days after, any dose of study vaccine.
• Has received chronic administration (defined as > 14 total days) of immunosuppressants or other immune-modifying drugs within 6 months before the first study vaccine dose.
• Has received immunoglobulins and/or blood products within the 3 months before the first study vaccine dose or has plans for administration during the study period.
• Has a positive test result at the Screening Visit for hepatitis B surface antigen, hepatitis C virus antibody, or HIV type 1 or 2 antibodies.
• Has donated > 450 mL of whole blood or blood products within 30 days of enrollment or plans to do so during the study period.
• Is an immediate family member or household member of study personnel.
• Previously participated in an investigational study involving LNPs.
• Has a positive urine drug screen result at Screening for any of the following nonprescription drugs of abuse: amphetamines, benzodiazepines, cocaine, methadone, opiates, and phencyclidine.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 49 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT04064905
• Other Study ID Numbers: mRNA-1893-P101; BARDA HHS010020160029C ( Other Grant/Funding Number: Biomedical Advanced Research & Development Authority (BARDA) )
• Has Data Monitoring Committee: Yes

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

• Current Responsible Party: ModernaTX, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ModernaTX, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Biomedical Advanced Research and Development Authority
• Investigators: Not Provided
• PRS Account: ModernaTX, Inc.
• Verification Date: April 2021