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

Zika Virus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04064905
• Other study ID #: mRNA-1893-P101
• Secondary ID: BARDA HHS0100201
• Status: Completed
• Phase: Phase 1
• Start date: July 30, 2019
• Est. completion date: March 22, 2021

Study information

• Verified date: December 2023
• Source: ModernaTX, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical study will evaluate the safety, tolerability and reactogenicity of mRNA-1893 Zika vaccines in flavivirus seronegative and flavivirus seropositive participants

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: March 22, 2021
• Est. primary completion date: March 22, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

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 enzyme-linked immunosorbent assay (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.

Related Conditions & MeSH terms

• Zika Virus
• Zika Virus Infection

Intervention

Biological:
• mRNA-1893
Zika vaccine

Other:
• Placebo
0.9% sodium chloride

Locations

Country	Name	City	State
Puerto Rico	Ponce School of Medicine - CAIMED Center	Ponce
United States	Benchmark Research	Austin	Texas
United States	Benchmark Research	Fort Worth	Texas
United States	Meridan Clinical Research	Omaha	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
ModernaTX, Inc.	Biomedical Advanced Research and Development Authority

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Solicited Local and Systemic Reactogenicity Adverse Reaction (ARs)-First Vaccination	Solicited ARs (local and systemic) were collected in the daily diary. Local ARs included: injection site pain, injection site erythema, and injection site induration/swelling. Systemic ARs included: body temperature (oral), generalized myalgia (muscle ache or pain), generalized arthralgia (joint ache or pain), headache, fatigue/malaise (unusual tiredness), nausea/vomiting, chills, and rash. Data for this outcome measure is reported up to 7 days after the first study vaccination only. A summary of all serious adverse events (SAEs) and all nonserious AEs ("Other"), regardless of causality, is in Reported "Adverse Events" section.	Up to Day 7 after first vaccination (up to 8 days)
Primary	Number of Participants With Solicited Local and Systemic Reactogenicity Adverse Reaction (ARs)-Second Vaccination	Solicited ARs (local and systemic) were collected in the daily diary. Local ARs included: injection site pain, injection site erythema, and injection site induration/swelling. Systemic ARs included: body temperature (oral), generalized myalgia (muscle ache or pain), generalized arthralgia (joint ache or pain), headache, fatigue/malaise (unusual tiredness), nausea/vomiting, chills, and rash. Data for this outcome measure is reported up to 7 days after the second study vaccination only. A summary of all serious adverse events (SAEs) and all nonserious AEs ("Other"), regardless of causality, is in Reported "Adverse Events" section.	Up to Day 7 after second vaccination (Day 29 to Day 36)
Primary	Number of Participants With Unsolicited Adverse Events (AEs)	An unsolicited AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A treatment-emergent adverse event (TEAE) was as any AE not present before exposure to vaccine or any AE already present that worsened in intensity or frequency after exposure. A summary of all SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Day 1 to the end of study visit (up to Day 392)
Primary	Number of Participants With Adverse Event of Special Interest (AESI) and Serious Adverse Events (SAEs)	An SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions was a congenital anomaly/birth defect, or was an important medical event. AESIs included potentially immune-mediated medical conditions (autoimmune or autoinflammatory diseases) that may have the theoretical potential for association with novel vaccines. A summary of all SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.	Day 1 to the end of study visit (up to Day 392)
Secondary	Geometric Mean Titer (GMT) of Neutralizing Antibody (nAb) Against Zika Virus as Measured by Plaque Reduction Neutralization Test (PRNT50)	GMT 95% CI is calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation.	Day 1, 29, 57, Month 7 and 13
Secondary	Geometric Mean Titer of Neutralizing Antibody in Initially Seronegative Participants Against Zika Virus as Measured by Plaque Reduction Neutralization Test (PRNT50)	GMT 95% CI is calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation.	Day 1, 29, 57, Month 7 and 13
Secondary	Geometric Mean Titer of Neutralizing Antibody in Initially Seropositive Participants Against Zika Virus as Measured by Plaque Reduction Neutralization Test (PRNT50)	GMT 95% CI is calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation.	Day 1, 29, 57, Month 7 and 13
Secondary	Percentage of Participants Who Seroconverted From 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	Seroconversion is defined as a change of PRNT from below the lower limit of quantification (LLOQ) to a PRNT equal to or above LLOQ for the assay, or a multiplication by at least 4 in participants with pre-existing PRNT titers.	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.
Secondary	Number of Initially Seronegative Participants With a Seroresponse as Measured by Plaque Reduction Neutralization Test	Seroconversion is defined as a change of PRNT from below the LLOQ to a PRNT equal to or above LLOQ for the assay, or a multiplication by at least 4 in participants with pre-existing PRNT titers.	Day 29, Day 57, Month 7, and Month 13
Secondary	Number of Initially Seropositive Participants With a 2-fold or 4-fold Increase in Neutralizing Antibody Titers as Compared With Baseline as Measured by Plaque Reduction Neutralization Test	Seroconversion is defined as a change of Plaque Reduction Neutralization Test from below the lower limit of quantification (LLOQ) to a PRNT equal to or above LLOQ for the assay, or a multiplication by at least 4 in participants with pre-existing PRNT titers.	Day 29, Day 57, Month 7, and Month 13