A Controlled Human Infection Model (CHIM) is being developed to provide early proof-of-concept that experimental infection with the intestinal nematode, Trichuris trichiura, is feasible and safe. The proposed model consists of enrolling consenting, healthy, trichuriasis-naïve adults and challenging them with the investigational product, Trichuris trichiura Egg Inoculum, to assess their ability to result in detectable infection. The proposed study will be a feasibility study that will consist of administering different doses of the Trichuris trichiura Egg Inoculum to healthy adult volunteers to determine the optimal dose (i.e., number of T. trichiura eggs) that is safe, well-tolerated and results in consistent infection.
Open-label, dose-escalation clinical study in healthy, trichuriasis-naïve adults: Study sites: * George Washington University, Washington, DC * Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD * Number of participants: up to 18 in 3 cohorts of 6 volunteers each In Cohort 1, six (6) volunteers will receive an inoculum of 150 embryonated Trichuris trichiura eggs. In Cohort 2, six (6) volunteers will receive an inoculum of 300 embryonated Trichuris trichiura eggs. In the optional Cohort 3, six (6) volunteers will receive an inoculum of 450 embryonated Trichuris trichiura eggs. The cohorts will be enrolled in a staggered fashion with safety data assessed prior to larval dose escalation. Cohort 2 will be inoculated no earlier than 16 weeks after the last volunteer is inoculated in Cohort 1. The optional Cohort 3 will be inoculated no sooner than 16 weeks after the last volunteer is inoculated in Cohort 2. Cohort 3 will be enrolled only if the tolerability of the experimental infection of Cohort 2 is acceptable and does not result in significant adverse events. * Egg administration schedule: Study Day 0 (single administration) * Route: oral * Doses of T. trichiura Egg Inoculum to be tested: 150, 300 and 450 embryonated eggs (high dose optional) * Study duration: approximately 10 months per study participant
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Trichuris trichiura Egg Inoculum that will be used in this study is manufactured by obtaining T. trichiura eggs from the feces of a chronically infected human volunteer, who is negative for HIV, HBV, and HCV. Fecal material is processed following a qualified standard procedure, and after isolating eggs, they are stored at 2-8oC until use. Controls for the manufacturing process are tests for viability (microscopy of larval hatching), species identification (PCR), and microbial bioburden of the eggs.
George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, United States
RECRUITINGNIH Clinical Center
Bethesda, Maryland, United States
RECRUITINGSolicited adverse events, graded by severity
Frequency of solicited adverse events, graded by severity, from the day of CHTI through study Day 182.
Time frame: Day of CHTI through study Day 182
Serious Adverse Events
Frequency of CHTI-related Serious Adverse Events from the time of administration of the T. trichiura Egg Inoculum through the final study visit
Time frame: Day of CHTI through final study visit on study Day 203
Unsolicited adverse events
Frequency of unsolicited adverse events, graded by severity, from the time of CHTI through treatment with albendazole (Day 182)
Time frame: Day of CHTI through study Day 182
New-onset chronic medical conditions
Frequency of new-onset chronic medical conditions through the final study visit
Time frame: Day of CHTI through final study visit on study Day 203
Adverse Events of Special Interest
Frequency of Adverse Events of Special Interest through the final study visit
Time frame: Day of CHTI through final study visit on study Day 203
Adverse events related to abnormal clinical safety laboratory parameter (white blood cell count) values
Frequency of clinical safety laboratory adverse events related to abnormal white blood cell count (unit of measure = cells/mm\^3)
Time frame: Day of CHTI through final study visit on study Day 203
Adverse events related to abnormal clinical safety laboratory parameter (absolute eosinophil count) values
Frequency of clinical safety laboratory adverse events related to abnormal eosinophil count (unit of measure = cells/mm\^3)
Time frame: Day of CHTI through final study visit on study Day 203
Adverse events related to abnormal clinical safety laboratory parameter (platelet count) values
Frequency of clinical safety laboratory adverse events related to abnormal platelet count (unit of measure = cells/mm\^3)
Time frame: Day of CHTI through final study visit on study Day 203
Adverse events related to abnormal clinical safety laboratory parameter (hemoglobin concentration) values
Frequency of clinical safety laboratory adverse events related to abnormal hemoglobin concentration (unit of measure = g/dL)
Time frame: Day of CHTI through final study visit on study Day 203
Adverse events related to abnormal clinical safety laboratory parameter (serum creatinine concentration) values
Frequency of clinical safety laboratory adverse events related to abnormal serum creatinine concentration (unit of measure = mg/dL)
Time frame: Day of CHTI through final study visit on study Day 203
Adverse events related to abnormal clinical safety laboratory parameter (serum alanine aminotransferase concentration) values
Frequency of clinical safety laboratory adverse events related to abnormal serum alanine aminotransferase (ALT) concentration (unit of measure = U/L)
Time frame: Day of CHTI through final study visit on study Day 203
Fecal egg detection
Proportion of participants with detectable T. trichiura eggs, at any time point, in fecal samples, as determined by microscopy using the qualified saline flotation technique
Time frame: Day of CHTI through study Day 182
Fecal egg counts
Fecal egg counts as determined by microscopy using the qualified McMaster method, during Weeks 12 through 26 post-CHTI
Time frame: Weeks 12 through 26 post-CHTI
T. trichiura DNA in fecal samples
Levels of T. trichiura DNA in fecal samples, as measured by qPCR, during Weeks 12 through 26 post-CHTI
Time frame: Weeks 12 through 26 post-CHTI
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