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

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ClinicalTrials.gov Identifier: NCT05123222
Recruitment Status : Recruiting
First Posted : November 17, 2021
Last Update Posted : April 15, 2022
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This study will include 5 cohorts of 14 flavivirus-naïve female subjects, 18 - 40 years of age (total: up to 70 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. Cohorts 3 and 4 may be enrolled if dose escalation criteria are met (Section 3.1.2.3). Enrollment into Cohort 5 may occur if dose escalation criteria are met following enrollment into Cohorts 3 and 4. Only one ZIKV strain will be evaluated in Cohort 5.

Condition or disease Intervention/treatment Phase
Zika Virus Other: ZIKV-SJRP/2016-184 Strain Other: Experimental: ZIKV-Nicaragua/2016 Strain Biological: Placebo Phase 1

Detailed Description:
This study is a placebo-controlled, double-blind study in normal healthy adult 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, flavivirus-naïve, 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 and 10^3 PFU. Only one of the ZIKV strains will be studied at a dose of 10^4 PFU. The ZIKV strain to be studied at 10^4 PFU will be determined following review of the data from the 10^2 and 10^3 PFU cohorts. Placebo recipients are included in the study as a control to better assess ZIKV-associated versus non-ZIKV-associated AEs.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: This study will include 5 cohorts of 14 flavivirus-naïve female subjects, 18 - 40 years of age (total: up to 70 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. Cohorts 3 and 4 may be enrolled if dose escalation criteria are met (Section 3.1.2.3). Enrollment into Cohort 5 may occur if dose escalation criteria are met following enrollment into Cohorts 3 and 4. Only one ZIKV strain will be evaluated in Cohort 5.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase I Evaluation of Two Zika Viruses for Use in Controlled Human Infection Models (CHIM)
Actual Study Start Date : February 16, 2022
Estimated Primary Completion Date : April 14, 2023
Estimated Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ZIKV-SJRP/2016-184 Strain
Dose of 10ˆ2 PFU Dose escalation of 10ˆ3 PFU Dose escalation of 10ˆ4 PFU
Other: ZIKV-SJRP/2016-184 Strain
Zika Virus Strain

Experimental: ZIKV-Nicaragua/2016 Strain
Dose of 10ˆ2 PFU Dose escalation of Dose of 10ˆ3 PFU Dose escalation of 10ˆ4 PFU
Other: Experimental: ZIKV-Nicaragua/2016 Strain
Zike Virus Strain

Placebo Comparator: Placebo Biological: Placebo
Not an active strain of Zika




Primary Outcome Measures :
  1. Response rate of both ZIKV Strains for use in a safety-assured Zika CHIM [ Time Frame: Thru 90 days post-administration of the ZIKV strain. ]
  2. The frequency and severity of clinical signs and symptoms of infection [ Time Frame: Thru 90 days post-administration of the ZIKV strain. ]
  3. The infection frequency of ZIKV by strain and by dose [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
  4. The frequency, magnitude, and duration of ZIKV presence in the blood, urine, cervico-vaginal secretions, and saliva [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
    Measured by RT-PCR and virus titration in tissue culture by ZIKV strain and dose.

  5. Find a suitable ZIKV CHIM Strain [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
    Defined as ≥ 80% of flavivirus-naïve inoculated subjects develop detectable viremia by virus culture (infectious virus) and Infectious virus is detected on more than 1 day for ≥ 80% of subjects with detectable viremia and The mean peak titer of infectious virus recovered from subjects is 2 - 3.0 log10 PFU/mL


Secondary Outcome Measures :
  1. Characterize the clinical presentation of acute ZIKV infection by assessing the frequency of adverse events (AEs) Adverse Events [ Time Frame: Thru 28 days of ZIKV administration ]
    Graded by severity

  2. Determine the quantity and duration of ZIKV presence using peak virus teter [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
    determined by RT-PCR

  3. Determine the quantity and duration of ZIKV presence using peak virus teter [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
    determined by virus culture

  4. Determine the quantity and duration of ZIKV presence shedding saliva [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
    determined by RT-PCR

  5. Determine the quantity and duration of ZIKV presence shedding saliva [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
    determined by virus culture

  6. Determine the quantity and duration of ZIKV presence shedding in urine [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
    determined by RT-PCR

  7. Determine the quantity and duration of ZIKV presence shedding in urine [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
    determined by virus culture

  8. Magnitude of serum neutralizing antibody response in patients who received administration of ZIKV infection. [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
    Measured by PK blood test

  9. Determine the peak neutralizing antibody response to ZIKV [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult flavivirus-naïve 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 16 days (or longer for safety if necessary) following receipt of ZIKV or placebo.
  • All subjects: Willingness to use barrier contraception during cervico-vaginal, anal, and oral intercourse for the duration of the study.
  • Female subjects of childbearing potential must be willing to use effective contraception for the duration of the study. Reliable methods of contraception include: hormonal birth control* (implantable, hormonal patch, NuvaRing®, 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, DENV infection, yellow fever virus infection, St Louis Encephalitis virus or West Nile virus infection.
  • Previous receipt of a flavivirus 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.
  • Refusal to allow storage of specimens for future research.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05123222


Contacts
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Contact: Madeleine Blunt (443) 610-8568 mblunt2@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins University, Bloomberg School of Public Health Recruiting
Baltimore, Maryland, United States, 21202
Contact: Madeleine Blunt, MD    443-610-8568    mblunt2@jhmi.edu   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Anna Durbin, MD Johns Hopkins University
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT05123222    
Other Study ID Numbers: CIR 316
First Posted: November 17, 2021    Key Record Dates
Last Update Posted: April 15, 2022
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zika virus
Additional relevant MeSH terms:
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Zika Virus Infection
Infections
Virus Diseases
Arbovirus Infections
Vector Borne Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections