Clinical trial NCT04064905: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Zika Virus
Keywords: mRNA-1893
zika vaccine
Moderna
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2019-08-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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


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 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.

Primary outcomes:
measure: Number of Participants With Solicited Local and Systemic Reactogenicity Adverse Reaction (ARs)-First Vaccination
timeFrame: Up to Day 7 after first vaccination (up to 8 days)
measure: Number of Participants With Solicited Local and Systemic Reactogenicity Adverse Reaction (ARs)-Second Vaccination
timeFrame: Up to Day 7 after second vaccination (Day 29 to Day 36)
measure: Number of Participants With Unsolicited Adverse Events (AEs)
timeFrame: Up to Day 392 (all AEs considered an SAE were collected till end of study [Day 392]; the Other AEs [non-SAE] were collected up to Day 57)
measure: Number of Participants With Adverse Event of Special Interest (AESI) and Serious Adverse Events (SAEs)
timeFrame: Day 1 to the end of study visit (up to Day 392)
Secondary outcomes:
measure: Geometric Mean Titer (GMT) of Neutralizing Antibody (nAb) Against Zika Virus as Measured by Plaque Reduction Neutralization Test (PRNT50)
timeFrame: Day 1, 29, 57, Month 7 and 13
measure: Geometric Mean Titer of Neutralizing Antibody in Initially Seronegative Participants Against Zika Virus as Measured by Plaque Reduction Neutralization Test (PRNT50)
timeFrame: Day 1, 29, 57, Month 7 and 13
measure: Geometric Mean Titer of Neutralizing Antibody in Initially Seropositive Participants Against Zika Virus as Measured by Plaque Reduction Neutralization Test (PRNT50)
timeFrame: Day 1, 29, 57, Month 7 and 13
measure: 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
timeFrame: 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.
measure: Number of Initially Seronegative Participants With a Seroresponse as Measured by Plaque Reduction Neutralization Test
timeFrame: Day 29, Day 57, Month 7, and Month 13
measure: 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
timeFrame: Day 29, Day 57, Month 7, and Month 13
Other outcomes:
Locations:
city: Omaha
country: United States
facility: Meridan Clinical Research
state: Nebraska
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research
state: Texas
city: Ponce
country: Puerto Rico
facility: Ponce School of Medicine - CAIMED Center
Study officials:
References: