Clinical trial NCT03611946: Evaluation of the Safety and Immunogenicity of the Live Attenuated Zika Vaccine rZIKV/D4Δ30-713 in Flavivirus-naïve Adults
Official title: Phase I Evaluation of the Safety and Immunogenicity of the Live Attenuated Zika Vaccine rZIKV/D4Δ30-713 in Flavivirus-naïve Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Zika Virus
Keywords: Zika virus
Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2018-08-02
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of a single dose of the live attenuated Zika vaccine rZIKV/D4Δ30-713 in adults with no history of previous flavivirus infection.

Detailed description: This study will evaluate the safety, reactogenicity, and immunogenicity of a single dose of the live attenuated Zika vaccine rZIKV/D4Δ30-713 in adults with no history of previous flavivirus infection.

Participants will be randomly assigned to receive a single dose of either rZIKV/D4Δ30-713 or placebo at study entry (Day 0).

Study visits will occur on Days 0, 4, 6, 8, 10, 12, 14, 16, 21, 28, 56, 90, 150, and 180. Visits may include a physical examination; blood, urine, saliva, nasopharyngeal (NP) or midturbinate swab, vaginal secretions, and semen collection; and pregnancy testing.

SARS-CoV-2 PCR (nasopharyngeal or mid-turbinate swab) will be performed during screening and on days 0, 8, and 14.

Eligibility criteria: Inclusion Criteria:

* Adult male or female between 18 and 50 years of age, inclusive.
* Good general health as determined by physical examination, laboratory screening, and review of medical history.
* Available for the duration of the study, which is approximately 26 weeks.
* Willingness to participate in the study as evidenced by signing the informed consent document.
* Females only: Female subjects of childbearing potential, with the exception noted below, should be willing to use effective contraception and have no plans to undergo IVF (in vitro fertilization) during participation in the trial. Reliable methods of contraception include hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, and intrauterine device. Women must have been on an effective method of birth control for at least 30 days prior to enrollment. All female subjects will be considered as having childbearing potential, except for women who exclusively have sex with women, those who have had a hysterectomy, tubal ligation, or tubal coil (at least 3 months prior to vaccination), or are considered to be post-menopausal, as documented by at least 1 year since last menstrual period with a follicle-stimulating hormone (FSH) level in the menopausal range or at least 24 consecutive months of amenorrhea. Transgender men who have internal female organs and have sex with men will be considered of childbearing potential and should be willing to use effective contraception during the trial. Exception: Females who have sex with females (exclusively) and have no intention of conceiving a child during the study and women whose partners have had a vasectomy will not be required to use contraception, however they will be required to use female condoms and/or dental dams for at least 1 month following vaccination. For women whose sexual partner has had a vasectomy, the vasectomy must have been performed 30 days or more prior to enrollment.
* Males only: Males of reproductive potential should be willing to use barrier contraception for the first 3 months following vaccination\* and agree to not donate sperm for the duration of the study.

  * Based on CDC guidance for men returning from ZIKV-endemic areas

Exclusion Criteria:

* Females only: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test, or breast-feeding.
* Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease based on history, physical examination, and/or laboratory studies.
* Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the subject's ability to understand and cooperate with the requirements of the study protocol.
* Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in this protocol.
* Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, or would render the subject unable to comply with the protocol.
* Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by subject history.
* History of a severe allergic reaction or anaphylaxis.
* Severe asthma (emergency room visit or hospitalization within the last 6 months).
* HIV infection, as indicated by screening and confirmatory assays.
* Hepatitis C virus (HCV) infection, as indicated by screening and confirmatory assays.
* Hepatitis B virus (HBV) infection, as indicated by hepatitis B surface antigen (HBsAg) screening.
* Any known immunodeficiency syndrome.
* History of Guillain-Barrè syndrome.
* Current use of anticoagulant medications (this does not include anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications).
* Use of immunosuppressive corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following inoculation. An immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg of a prednisone equivalent per day for greater than or equal to 14 days.
* Receipt of a live vaccine within 28 days or a killed vaccine within 14 days prior to inoculation, or anticipated receipt of any vaccine during the 28 days following inoculation with the exception of COVID-19 vaccines either licensed or under EUA which can be given at any time, however all effort will be made to avoid giving COVID-19 vaccines within the above windows.
* Asplenia.
* Receipt of blood products within the past 6 months, including transfusions or immunoglobulin, or anticipated receipt of any blood products or immunoglobulin during the 28 days following inoculation.
* History or serologic evidence of previous ZIKV or other flavivirus infection (e.g., dengue, yellow fever virus, St. Louis Encephalitis virus, or West Nile virus).
* Previous receipt of a flavivirus vaccine (licensed or experimental).
* Receipt or anticipated receipt of any investigational agent in the 28 days before or after inoculation with the exception of COVID-19 vaccines, either licensed or authorized under EUA.
* Refusal to allow specimen storage for future research.
* Is in isolation or quarantine for SARS-CoV-2 infection or exposure and cannot complete screening or enrollment for this reason.

Primary outcomes:
measure: Frequency of solicited local and general adverse events (AEs)
timeFrame: Measured through Day 28
measure: Frequency of unsolicited AEs
timeFrame: Measured through Day 28
measure: Frequency of medically-attended AEs and serious adverse events (SAEs)
timeFrame: Measured through Day 90
measure: Peak neutralizing antibody titer to ZIKV with either 103 PFU or 104 PFU of rZIKV/D4Δ30
timeFrame: Measured through Day 90
Secondary outcomes:
measure: Frequency of viremia
timeFrame: Measured through Day 180
measure: Determination of the neutralizing antibody titer to ZIKV
timeFrame: Measured through Day 180
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University, Bloomberg School of Public Health
state: Maryland
city: Burlington
country: United States
facility: University of Vermont Medical Center (UVMMC), Clinical Research Center
state: Vermont
Study officials:
affiliation: Center for Immunization Research, Johns Hopkins School of Public Health
name: Anna Durbin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Vermont
name: Kristen Pierce, MD
role: PRINCIPAL_INVESTIGATOR
References: