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

NCT05123222 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CIR 316
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Zika Virus

Keywords

Zika virus

Outcome Measures

Primary Outcomes (6)

• Number of Solicited Adverse Events

  measured by count of solicited adverse events recorded following ZIKV administration

  Through 90 days post-inoculation

• Severity of Adverse Events

  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.

  Through 90 days post-inoculation

• Number of Participants Infected by ZIKV

  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)

  Through 90 days post-inoculation

• Number of Participants With Zika Virus Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva

  Count of participants with infectious virus recovered from serum, whole blood, cervicovaginal secretions (CVS), semen, urine, and saliva as measured by RT-PCR

  Through 90 days post-inoculation

• Magnitude of ZIKV Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva

  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.

  Through 90 days post-inoculation

• Duration of ZIKV in Serum, Whole Blood, CVS, Semen, Urine, and Saliva

  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

  Through 90 days post-inoculation

Secondary Outcomes (5)

• 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

• 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

Study Arms (4)

Cohort 1 - SJRP

EXPERIMENTAL

ZIKV-SJRP/2016-184 injected at dose of 10\^2 PFU.

Biological: ZIKV-SJRP/2016-184 Strain

Cohort 1 - Placebo

PLACEBO COMPARATOR

Volume matched placebo injection (saline)

Biological: Placebo

Cohort 2 - Nicaragua

EXPERIMENTAL

ZIKV-Nicaragua/2016 injected at dose of 10\^2 PFU.

Biological: Experimental: ZIKV-Nicaragua/2016 Strain

Cohort 2 - Placebo

PLACEBO COMPARATOR

Volume matched placebo injection (saline)

Biological: Placebo

Interventions

ZIKV-SJRP/2016-184 Strain BIOLOGICAL

Zika Virus Strain (San Jose Rio Puerto)

Cohort 1 - SJRP

Experimental: ZIKV-Nicaragua/2016 Strain BIOLOGICAL

Zika Virus Strain (Nicaragua)

Cohort 2 - Nicaragua

Placebo BIOLOGICAL

Saline

Cohort 1 - Placebo; Cohort 2 - Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Johns Hopkins University, Bloomberg School of Public Health

Baltimore, Maryland, 21202, United States

Location

MeSH Terms

Conditions

Zika Virus Infection

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections

Results Point of Contact

• Title: Anna Durbin
• Organization: Center for Immunization Research

adurbin1@jhu.edu

667-306-9772

Study Officials

• Anna Durbin, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: This study will include 4 cohorts of 14 ZIKV and DENV-naïve non-pregnant female and male subjects, 18 - 40 years of age (total: 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. Two strains of ZIKV will be evaluated in both men and women- San Jose Rio Puerto (Cohorts 1 and 3) and Nicaragua (Cohorts 2 and 4).

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: November 17, 2021
• Study Start: February 16, 2022
• Primary Completion: September 3, 2024
• Study Completion: September 3, 2024
• Last Updated: April 11, 2025
• Results First Posted: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)