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

• ClinicalTrials.gov Identifier: NCT05123222
• Recruitment Status: Recruiting
• First Posted: November 17, 2021
• Last Update Posted: March 6, 2023
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information

• First Submitted Date: October 26, 2021
• First Posted Date: November 17, 2021
• Last Update Posted Date: March 6, 2023
• Actual Study Start Date: February 16, 2022
• Estimated Primary Completion Date: April 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 26, 2022)

• 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. ]
• The frequency and severity of clinical signs and symptoms of infection [ Time Frame: Thru 90 days post-administration of the ZIKV strain. ]
• The infection frequency of ZIKV by strain and by dose [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
• 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.
• Find a suitable ZIKV CHIM Strain [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
  Defined as ≥ 80% of ZIKV and DENV-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

Original Primary Outcome Measures (submitted: November 5, 2021)

• 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. ]
• The frequency and severity of clinical signs and symptoms of infection [ Time Frame: Thru 90 days post-administration of the ZIKV strain. ]
• The infection frequency of ZIKV by strain and by dose [ Time Frame: Thru 90 days post-administration of the ZIKV strain ]
• 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.
• 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

Current Secondary Outcome Measures (submitted: November 5, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• Brief Summary: This study will include 5 cohorts of 14 ZIKV and DENV-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.
• 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, ZIKV and DENV-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.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

This study will include 5 cohorts of 14 ZIKV and DENV-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

• Condition: Zika Virus

Intervention

• Other: ZIKV-SJRP/2016-184 Strain
  Zika Virus Strain
• Other: Experimental: ZIKV-Nicaragua/2016 Strain
  Zike Virus Strain
• Biological: Placebo
  Not an active strain of Zika

Study Arms

• Experimental: ZIKV-SJRP/2016-184 Strain
  Dose of 10ˆ2 PFU Dose escalation of 10ˆ3 PFU Dose escalation of 10ˆ4 PFU
  Intervention: Other: ZIKV-SJRP/2016-184 Strain
• Experimental: ZIKV-Nicaragua/2016 Strain
  Dose of 10ˆ2 PFU Dose escalation of Dose of 10ˆ3 PFU Dose escalation of 10ˆ4 PFU
  Intervention: Other: Experimental: ZIKV-Nicaragua/2016 Strain
• Placebo Comparator: Placebo
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 5, 2021): 70
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2023
• Estimated Primary Completion Date: April 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 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, 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05123222
• Other Study ID Numbers: CIR 316
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Anna Durbin, MD; Johns Hopkins University

• PRS Account: National Institute of Allergy and Infectious Diseases (NIAID)
• Verification Date: March 2023