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

Primary Purpose

Zika Virus

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ZIKV-SJRP/2016-184 Strain
Experimental: ZIKV-Nicaragua/2016 Strain
Placebo
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Zika Virus focused on measuring Zika virus

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Adult ZIKV and DENV-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 through study day 56 (in accordance with CDC guidance).
  • 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 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.
  • Refusal to allow storage of specimens for future research.

Sites / Locations

  • Johns Hopkins University, Bloomberg School of Public HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

ZIKV-SJRP/2016-184 Strain

ZIKV-Nicaragua/2016 Strain

Placebo

Arm Description

Dose of 10ˆ2 PFU

Dose of 10ˆ2 PFU

PlasmaLyte

Outcomes

Primary Outcome Measures

The frequency and severity of clinical signs and symptoms of infection
The infection frequency of ZIKV by strain and by dose
defined by recovery of ZIKV by RT-PCR or virus culture
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

Secondary Outcome Measures

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

Full Information

First Posted
October 26, 2021
Last Updated
October 12, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT05123222
Brief Title
Evaluation of Two Zika Viruses for Use in Controlled Human Infection Models (CHIM)
Official Title
Phase I Evaluation of Two Zika Viruses for Use in Controlled Human Infection Models (CHIM)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 16, 2022 (Actual)
Primary Completion Date
July 31, 2024 (Anticipated)
Study Completion Date
August 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Zika Virus
Keywords
Zika virus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ZIKV-SJRP/2016-184 Strain
Arm Type
Experimental
Arm Description
Dose of 10ˆ2 PFU
Arm Title
ZIKV-Nicaragua/2016 Strain
Arm Type
Experimental
Arm Description
Dose of 10ˆ2 PFU
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
PlasmaLyte
Intervention Type
Other
Intervention Name(s)
ZIKV-SJRP/2016-184 Strain
Intervention Description
Zika Virus Strain
Intervention Type
Other
Intervention Name(s)
Experimental: ZIKV-Nicaragua/2016 Strain
Intervention Description
Zika Virus Strain
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Not an active strain of Zika
Primary Outcome Measure Information:
Title
The frequency and severity of clinical signs and symptoms of infection
Time Frame
Thru 90 days post-administration of the ZIKV strain.
Title
The infection frequency of ZIKV by strain and by dose
Description
defined by recovery of ZIKV by RT-PCR or virus culture
Time Frame
Thru 90 days post-administration of the ZIKV strain
Title
The frequency, magnitude, and duration of ZIKV presence in the blood, urine, cervico-vaginal secretions, semen, and saliva
Description
measured by RT-PCR and virus titration in tissue culture by ZIKV strain and dose
Time Frame
Thru 90 days post-administration of the ZIKV strain
Secondary Outcome Measure Information:
Title
Characterize the clinical presentation of acute ZIKV infection by assessing the frequency of adverse events (AEs) Adverse Events
Description
graded by severity
Time Frame
Thru 28 days of ZIKV administration
Title
Determine the quantity and duration of ZIKV presence using peak virus titer in blood
Description
determined by RT-PCR and virus culture
Time Frame
Thru 90 days post-administration of the ZIKV strain
Title
Determine the quantity and duration of ZIKV presence using peak virus titer shedding in saliva
Description
determined by RT-PCR and virus culture
Time Frame
Thru 90 days post-administration of the ZIKV strain
Title
Determine the quantity and duration of ZIKV presence shedding in urine
Description
determined by RT-PCR and virus culture
Time Frame
Thru 90 days post-administration of the ZIKV strain
Title
Determine the quantity and duration of ZIKV presence shedding in cervico-vaginal secretions
Description
determined by RT-PCR and virus culture
Time Frame
Thru 90 days post-administration of the ZIKV strain
Title
Determine the quantity and duration of ZIKV shedding in semen
Description
determined by RT-PCR and virus culture
Time Frame
Thru 90 days post-administration of the ZIKV strain
Title
Magnitude of serum neutralizing antibody response in patients who received administration of ZIKV infection.
Description
measured by PK blood test
Time Frame
Thru 180 days post-administration of the ZIKV strain
Title
Determine the peak neutralizing antibody response to ZIKV
Time Frame
Thru 180 days post-administration of the ZIKV strain

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ruby Pritchett
Phone
(410) 955-2791
Email
rpritch1@jhu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna Durbin, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University, Bloomberg School of Public Health
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruby Pritchett
Phone
410-955-2791
Email
rpritch1@jhu.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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