Phase I Evaluation of Two Zika Viruses for Use in Controlled Human Infection Models (CHIM)
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 56
- Locations
- 1
- Primary Endpoint
- Number of Solicited Adverse Events
Study Overview
Brief Summary
This study will include 4 cohorts of 14 ZIKV and DENV-naïve female and male subjects, 18 - 40 years of age (total: up to 56 subjects). Within each cohort, 10 subjects will receive ZIKV and 4 subjects will receive a placebo on Study Day 0. Cohorts 1 and 2 (Dose = 10^2 PFU) will be enrolled first and will enroll only women. Cohorts 3 and 4 (Dose = 10^2 PFU) will enroll men.
Detailed Description
This study is a placebo-controlled, double-blind study in normal healthy adult male and non-pregnant female subjects 18 - 40 years of age, inclusive, recruited from the metropolitan Baltimore/Washington, DC and Burlington, VT areas. The purpose of this study is to evaluate the clinical and virologic response to escalating doses of 2 different ZIKV strains administered subcutaneously in healthy, ZIKV and DENV-naïve, male and non-pregnant, female adult volunteers to identify the most suitable ZIKV strain and dose for use in a ZIKV CHIM. The ZIKV CHIM will then be used to evaluate the protective efficacy of candidate ZIKV vaccines prior to evaluation of these candidates in Phase 2 clinical trials. Both ZIKV strains will be studied at doses of 10^2 PFU. Placebo recipients are included in the study as a control to better assess ZIKV-associated versus non-ZIKV-associated AEs.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 40 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Adult ZIKV and DENV-naïve male and non-pregnant females 18 - 40 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, approximately 26 weeks post-inoculation.
- •Must be able to complete the informed consent process and comprehension assessment independently and without assistance.
- •Willingness to participate in the study as evidenced by signing the informed consent document.
- •Willingness to reside in the inpatient unit for 9 days (or longer for safety if necessary) following receipt of ZIKV or placebo.
- •Male subjects: Willingness to use barrier contraception during cervico-vaginal, anal, and oral intercourse through study day 90 (in accordance with CDC guidance).
- •Female subjects: Willingness to use barrier contraception during cervico-vaginal, anal, and oral intercourse through study day 56 (in accordance with CDC guidance).
- •Female subjects of childbearing potential must be willing to use effective contraception while at risk of Zika infection. CDC guidelines for the use of effective contraception of 8 weeks post-infection will be followed; time of infection is defined as inoculation with challenge virus. Reliable methods of contraception include: hormonal birth control* (implantable, hormonal patch, hormonal vaginal ring, oral contraception, Depo-Provera injection, etc.), surgical sterilization (hysterectomy, tubal ligation, or tubal coil at least 3 months prior to inoculation), and intrauterine device. All female subjects will be considered having child-bearing potential except for those with post-menopausal status documented as at least 1 year since last menstrual period and females who have sex with females (exclusively) and have no intention of conceiving a child during the study. Females who are not considered to be of childbearing potential will not be required to use contraception other than barrier contraception for the purpose of reducing potential transmission.
- •Volunteers on hormonal birth control must not be on medications or other agents that decrease the effectiveness of hormonal birth control.
Exclusion Criteria
- •Currently pregnant, as determined by positive beta-human choriogonadotropin (Beta-hCG) test, breast-feeding or planning to become pregnant during the 6-month duration of the study.
- •Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies.
- •Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the requirements of the study protocol.
- •Evidence of recent opiate use based on urine toxicology screen
- •Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), 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 which 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, by screening and confirmatory assays.
- •Hepatitis C virus (HCV) infection, by screening and confirmatory assays.
- •Hepatitis B virus (HBV) infection, by hepatitis B surface antigen (HBsAg) screening.
- •History of Guillain-Barré syndrome (GBS).
- •History of seizure disease or peripheral neuropathy
- •History of any neuroinflammatory disorder i.e. Bell's Palsy, transverse myelitis
- •Any known immunodeficiency syndrome, including that caused by malignancy.
- •Use of anticoagulant medications (use of antiplatelet medication such as aspirin or non-steroidal anti-inflammatory medication is permitted and will not exclude a subject from enrollment).
- •Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following inoculation. Immunosuppressive dose of corticosteroids is defined as ≥10 mg prednisone equivalent per day for ≥14 days.
- •Receipt of a live vaccine within 21 days or a killed vaccine within the 14 days prior to inoculation or anticipated receipt of any vaccine during the 21 days following inoculation.
- •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 infection or DENV infection.
- •Previous receipt of a ZIKV or DENV vaccine (licensed or investigational).
- •Anticipated receipt of any investigational agent in the 28 days before or after inoculation.
- •Subject has definite plans to travel to a ZIKV-endemic or dengue-endemic area during the study.
- •Previous hypersensitivity to any study product component.
- •Anaphylactic reaction to mosquito bites.
- •Refusal to allow storage of specimens for future research.
Arms & Interventions
Cohort 1 - SJRP
ZIKV-SJRP/2016-184 injected at dose of 10^2 PFU.
Intervention: ZIKV-SJRP/2016-184 Strain (Biological)
Cohort 1 - Placebo
Volume matched placebo injection (saline)
Intervention: Placebo (Biological)
Cohort 2 - Placebo
Volume matched placebo injection (saline)
Intervention: Placebo (Biological)
Outcomes
Primary Outcomes
Number of Solicited Adverse Events
Time Frame: Through 90 days post-inoculation
measured by count of solicited adverse events recorded following ZIKV administration
Duration of ZIKV in Serum, Whole Blood, CVS, Semen, Urine, and Saliva
Time Frame: Through 90 days post-inoculation
Mean number of days that ZIKV was recovered in serum, whole blood, cervicovaginal secretions (cvs), semen, urine, and saliva from participants with detectable zika as measured by RT-PCR
Severity of Adverse Events
Time Frame: Through 90 days post-inoculation
count of solicited AEs by severity grade 1 - mild, event that is easily tolerated, may require 1 dose of medication. grade 2 - moderate, event that interferes with daily activity or requires more than 1 dose of medication. grade 3 - severe, event that prevents daily activity and requires medical intervention. grade 4 - life-threatening, an adverse event that is deemed by the study clinician, the medical monitor, or an outside clinician caring for the subject to be a life-threatening event. grade 5 - death, any adverse event that results in the death of the subject.
Number of Participants Infected by ZIKV
Time Frame: Through 90 days post-inoculation
Infection defined as recovery of ZIKV by RT-PCR from blood and/or by seroconversion to ZIKV (50% plaque reduction neutralization titer \[PRNT50\]≥ 1:10)
Number of Participants With Zika Virus Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva
Time Frame: Through 90 days post-inoculation
Count of participants with infectious virus recovered from serum, whole blood, cervicovaginal secretions (CVS), semen, urine, and saliva as measured by RT-PCR
Magnitude of ZIKV Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva
Time Frame: Through 90 days post-inoculation
Mean peak titer of ZIKV recovered in serum, whole blood, cervicovaginal secretions (cvs), semen, urine, and saliva of participants by RT-PCR. Data are reported in Log10 Genome Equivalents (GE) per milliliter.
Secondary Outcomes
- Peak Virus Titer Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva(Through 90 days post-inoculation)
- Duration of ZIKV in Serum, Whole Blood, CVS, Semen, Urine, and Saliva(Through 90 days post-inoculation)
- Peak Neutralizing Antibody Response to ZIKV(Through 90 days post-inoculation)
- Frequency of AEs by Severity(Through 28 days post-inoculation)
- Number of Participants With Zika Virus Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva(Through 90 days post-inoculation)