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Controlled Human Infection Study of Orally Administered Trichuris Trichiura Eggs in Naïve Adults

Primary Purpose

Whipworm, Trichuriasis, Controlled Human Infection

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Trichuris trichiura Egg Inoculum
Sponsored by
George Washington University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Whipworm

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Males or females between 18 and 45 years, inclusive. Good general health as determined by means of the screening procedures. Available for the duration of the trial (approximately 7.5 months). Willingness to participate in the study as evidenced by signing the informed consent document. Exclusion Criteria: Pregnancy as determined by a positive urine human choriogonadotropin (hCG) (if female). Participant unwilling to use reliable contraception methods while participating in the study (if female of reproductive potential who is engaging in sexual activity that could lead to pregnancy); being of reproductive potential is defined as not being surgically sterile, abstinent from intercourse with a male partner, in a monogamous relationship with a vasectomized partner, at least 2 years post-menopausal, or determined otherwise by medical evaluation to be sterile. Currently lactating and breast-feeding (if female). Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies. Has a diagnosis of schizophrenia, bipolar disease or other major psychiatric condition that would make compliance with study visits/procedures difficult (e.g., subject with psychoses or history of suicide attempt or gesture in the 3 years before study entry, ongoing risk for suicide). Known or suspected immunodeficiency or immunosuppression as a result of an underlying illness or treatment. Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25-times the upper reference limit). Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit). Laboratory evidence of hematologic disease (hemoglobin <11.1 g/dl [females] or <12.5 g/dl [males]; absolute leukocyte count <3.4 or >11.0 x 103/mm3; absolute eosinophil count >0.6 x 103/mm3 or platelet count <125 x 103/mm3). Positive fecal occult blood test. Infection with a pathogenic intestinal helminth as determined by stool examination for ova and parasites. History of iron deficiency anemia or laboratory evidence of iron deficiency (serum ferritin concentration below the lower reference limit). Other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the participant unable to comply with the protocol. Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 24 months. Positive ELISA for hepatitis B surface antigen (HBsAg). Positive confirmatory test for HIV infection. Positive confirmatory test for hepatitis C virus (HCV) infection. Using or intends to continue using oral or parenteral corticosteroids, high-dose inhaled corticosteroids (>800 μg/day of beclomethasone dipropionate or equivalent) or other immunosuppressive or cytotoxic drugs within 30 days of the volunteer's expected enrollment in this study or planned use during the study. Known allergy to albendazole. History of previous infection with T. trichiura or continuous residence for more than 6 months in a T. trichiura-endemic area.

Sites / Locations

  • George Washington University Medical Faculty Associates
  • NIH Clinical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Trichuris trichiura Egg Inoculum 150 eggs

Trichuris trichiura Egg Inoculum 300 eggs

Trichuris trichiura Egg Inoculum 450 eggs

Arm Description

150 Trichuris trichiura eggs

300 Trichuris trichiura eggs

450 Trichuris trichiura eggs

Outcomes

Primary Outcome Measures

Solicited adverse events, graded by severity
Frequency of solicited adverse events, graded by severity, from the 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
Unsolicited adverse events
Frequency of unsolicited adverse events, graded by severity, from the time of CHTI through treatment with albendazole (Day 182)
New-onset chronic medical conditions
Frequency of new-onset chronic medical conditions through the final study visit
Adverse Events of Special Interest
Frequency of Adverse Events of Special Interest through the final study visit
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)
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)
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)
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)
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)
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)

Secondary Outcome Measures

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
Fecal egg counts
Fecal egg counts as determined by microscopy using the qualified McMaster method, during 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

Full Information

First Posted
December 27, 2022
Last Updated
August 14, 2023
Sponsor
George Washington University
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT05706116
Brief Title
Controlled Human Infection Study of Orally Administered Trichuris Trichiura Eggs in Naïve Adults
Official Title
A Controlled Human Infection Study of Orally Administered Trichuris Trichiura Eggs in Naïve Adults
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
September 23, 2025 (Anticipated)
Study Completion Date
March 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
George Washington University
Collaborators
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
No

5. Study Description

Brief Summary
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.
Detailed Description
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Whipworm, Trichuriasis, Controlled Human Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Trichuris trichiura Egg Inoculum 150 eggs
Arm Type
Experimental
Arm Description
150 Trichuris trichiura eggs
Arm Title
Trichuris trichiura Egg Inoculum 300 eggs
Arm Type
Experimental
Arm Description
300 Trichuris trichiura eggs
Arm Title
Trichuris trichiura Egg Inoculum 450 eggs
Arm Type
Experimental
Arm Description
450 Trichuris trichiura eggs
Intervention Type
Biological
Intervention Name(s)
Trichuris trichiura Egg Inoculum
Intervention Description
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.
Primary Outcome Measure Information:
Title
Solicited adverse events, graded by severity
Description
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
Title
Serious Adverse Events
Description
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
Title
Unsolicited adverse events
Description
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
Title
New-onset chronic medical conditions
Description
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
Title
Adverse Events of Special Interest
Description
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
Title
Adverse events related to abnormal clinical safety laboratory parameter (white blood cell count) values
Description
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
Title
Adverse events related to abnormal clinical safety laboratory parameter (absolute eosinophil count) values
Description
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
Title
Adverse events related to abnormal clinical safety laboratory parameter (platelet count) values
Description
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
Title
Adverse events related to abnormal clinical safety laboratory parameter (hemoglobin concentration) values
Description
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
Title
Adverse events related to abnormal clinical safety laboratory parameter (serum creatinine concentration) values
Description
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
Title
Adverse events related to abnormal clinical safety laboratory parameter (serum alanine aminotransferase concentration) values
Description
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
Secondary Outcome Measure Information:
Title
Fecal egg detection
Description
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
Title
Fecal egg counts
Description
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
Title
T. trichiura DNA in fecal samples
Description
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
Other Pre-specified Outcome Measures:
Title
Serum cytokine concentrations
Description
Serum cytokine concentrations during Weeks 12 through 26 post-CHTI
Time Frame
Weeks 12 through 26 post-CHTI
Title
Cytokine concentrations of supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with T. trichiura antigen
Description
Cytokine responses to stimulation with T. trichiura and other microbial antigens for total blood cells and peripheral blood monocytes (PBMCs) from the blood
Time Frame
Day of CHTI through final study visit on study Day 203
Title
Fecal microbiome
Description
Microbial communities present in the fecal samples by DNA and/or RNA sequencing analyses prior to and after exposure to T. trichiura Egg Inoculum
Time Frame
Day of CHTI through final study visit on study Day 203

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Males or females between 18 and 45 years, inclusive. Good general health as determined by means of the screening procedures. Available for the duration of the trial (approximately 7.5 months). Willingness to participate in the study as evidenced by signing the informed consent document. Exclusion Criteria: Pregnancy as determined by a positive urine human choriogonadotropin (hCG) (if female). Participant unwilling to use reliable contraception methods while participating in the study (if female of reproductive potential who is engaging in sexual activity that could lead to pregnancy); being of reproductive potential is defined as not being surgically sterile, abstinent from intercourse with a male partner, in a monogamous relationship with a vasectomized partner, at least 2 years post-menopausal, or determined otherwise by medical evaluation to be sterile. Currently lactating and breast-feeding (if female). Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies. Has a diagnosis of schizophrenia, bipolar disease or other major psychiatric condition that would make compliance with study visits/procedures difficult (e.g., subject with psychoses or history of suicide attempt or gesture in the 3 years before study entry, ongoing risk for suicide). Known or suspected immunodeficiency or immunosuppression as a result of an underlying illness or treatment. Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25-times the upper reference limit). Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit). Laboratory evidence of hematologic disease (hemoglobin <11.1 g/dl [females] or <12.5 g/dl [males]; absolute leukocyte count <3.4 or >11.0 x 103/mm3; absolute eosinophil count >0.6 x 103/mm3 or platelet count <125 x 103/mm3). Positive fecal occult blood test. Infection with a pathogenic intestinal helminth as determined by stool examination for ova and parasites. History of iron deficiency anemia or laboratory evidence of iron deficiency (serum ferritin concentration below the lower reference limit). Other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the participant unable to comply with the protocol. Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 24 months. Positive ELISA for hepatitis B surface antigen (HBsAg). Positive confirmatory test for HIV infection. Positive confirmatory test for hepatitis C virus (HCV) infection. Using or intends to continue using oral or parenteral corticosteroids, high-dose inhaled corticosteroids (>800 μg/day of beclomethasone dipropionate or equivalent) or other immunosuppressive or cytotoxic drugs within 30 days of the volunteer's expected enrollment in this study or planned use during the study. Known allergy to albendazole. History of previous infection with T. trichiura or continuous residence for more than 6 months in a T. trichiura-endemic area.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Diemert, MD
Phone
202-994-2909
Email
ddiemert@gwu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Laura Vasquez, MPH
Phone
202-994-1599
Email
lvasquez@gwu.edu
Facility Information:
Facility Name
George Washington University Medical Faculty Associates
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Thoreson, PA-C
Phone
202-741-2443
Email
cthoreson@mfa.gwu.edu
First Name & Middle Initial & Last Name & Degree
David J Diemert, MD
First Name & Middle Initial & Last Name & Degree
Elissa Malkin, DO
Facility Name
NIH Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Nutman, MD
Phone
301-496-5399
Email
tnutman@niaid.nih.gov
First Name & Middle Initial & Last Name & Degree
Thomas Nutman, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Controlled Human Infection Study of Orally Administered Trichuris Trichiura Eggs in Naïve Adults

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