Evaluation of Two Zika Viruses for Use in Controlled Human Infection Models (CHIM)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I Evaluation of Two Zika Viruses for Use in Controlled Human Infection Models (CHIM)

Conditions
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Zika Virus

Intervention / Treatment
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* Other: ZIKV-SJRP/2016-184 Strain
* Other: Experimental: ZIKV-Nicaragua/2016 Strain
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: This study will include 4 cohorts of 14 ZIKV and DENV-naïve non-pregnant 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZIKV-SJRP/2016-184 Strain<br>Dose of 10ˆ2 PFU | Other: ZIKV-SJRP/2016-184 Strain<br>* Zika Virus Strain<br>|
| Experimental: ZIKV-Nicaragua/2016 Strain<br>Dose of 10ˆ2 PFU | Other: Experimental: ZIKV-Nicaragua/2016 Strain<br>* Zika Virus Strain<br>|
| Placebo Comparator: Placebo<br>PlasmaLyte | Biological: Placebo<br>* Not an active strain of Zika<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The frequency and severity of clinical signs and symptoms of infection |  | Thru 90 days post-administration of the ZIKV strain. | 
| The infection frequency of ZIKV by strain and by dose | defined by recovery of ZIKV by RT-PCR or virus culture | Thru 90 days post-administration of the ZIKV strain | 
| The frequency, magnitude, and duration of ZIKV presence in the blood, urine, cervico-vaginal secretions, semen, and saliva | measured by RT-PCR and virus titration in tissue culture by ZIKV strain and dose | Thru 90 days post-administration of the ZIKV strain | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the clinical presentation of acute ZIKV infection by assessing the frequency of adverse events (AEs) Adverse Events | graded by severity | Thru 28 days of ZIKV administration | 
| Determine the quantity and duration of ZIKV presence using peak virus titer in blood | determined by RT-PCR and virus culture | Thru 90 days post-administration of the ZIKV strain | 
| Determine the quantity and duration of ZIKV presence using peak virus titer shedding in saliva | determined by RT-PCR and virus culture | Thru 90 days post-administration of the ZIKV strain | 
| Determine the quantity and duration of ZIKV presence shedding in urine | determined by RT-PCR and virus culture | Thru 90 days post-administration of the ZIKV strain | 
| Determine the quantity and duration of ZIKV presence shedding in cervico-vaginal secretions | determined by RT-PCR and virus culture | Thru 90 days post-administration of the ZIKV strain | 
| Determine the quantity and duration of ZIKV shedding in semen | determined by RT-PCR and virus culture | Thru 90 days post-administration of the ZIKV strain | 
| Magnitude of serum neutralizing antibody response in patients who received administration of ZIKV infection. | measured by PK blood test | Thru 180 days post-administration of the ZIKV strain | 
| Determine the peak neutralizing antibody response to ZIKV |  | Thru 180 days post-administration of the ZIKV strain | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zika virus