Clinical trial NCT05706116: 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
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Whipworm
Trichuriasis
Controlled Human Infection
Lead sponsor: George Washington University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2023-01-31
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

1. Males or females between 18 and 45 years, inclusive.
2. Good general health as determined by means of the screening procedures.
3. Available for the duration of the trial (approximately 7.5 months).
4. Willingness to participate in the study as evidenced by signing the informed consent document.

Exclusion Criteria:

1. Pregnancy as determined by a positive urine human choriogonadotropin (hCG) (if female).
2. 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.
3. Currently lactating and breast-feeding (if female).
4. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
5. 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).
6. Known or suspected immunodeficiency or immunosuppression as a result of an underlying illness or treatment.
7. Laboratory evidence of liver disease (alanine aminotransferase \[ALT\] greater than 1.25-times the upper reference limit).
8. Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit).
9. 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).
10. Positive fecal occult blood test.
11. Infection with a pathogenic intestinal helminth as determined by stool examination for ova and parasites.
12. History of iron deficiency anemia or laboratory evidence of iron deficiency (serum ferritin concentration below the lower reference limit).
13. 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.
14. Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 24 months.
15. Positive ELISA for hepatitis B surface antigen (HBsAg).
16. Positive confirmatory test for HIV infection.
17. Positive confirmatory test for hepatitis C virus (HCV) infection.
18. 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.
19. Known allergy to albendazole.
20. History of previous infection with T. trichiura or continuous residence for more than 6 months in a T. trichiura-endemic area.

Primary outcomes:
measure: Solicited adverse events, graded by severity
timeFrame: Day of CHTI through study Day 182
measure: Serious Adverse Events
timeFrame: Day of CHTI through final study visit on study Day 203
measure: Unsolicited adverse events
timeFrame: Day of CHTI through study Day 182
measure: New-onset chronic medical conditions
timeFrame: Day of CHTI through final study visit on study Day 203
measure: Adverse Events of Special Interest
timeFrame: Day of CHTI through final study visit on study Day 203
measure: Adverse events related to abnormal clinical safety laboratory parameter (white blood cell count) values
timeFrame: Day of CHTI through final study visit on study Day 203
measure: Adverse events related to abnormal clinical safety laboratory parameter (absolute eosinophil count) values
timeFrame: Day of CHTI through final study visit on study Day 203
measure: Adverse events related to abnormal clinical safety laboratory parameter (platelet count) values
timeFrame: Day of CHTI through final study visit on study Day 203
measure: Adverse events related to abnormal clinical safety laboratory parameter (hemoglobin concentration) values
timeFrame: Day of CHTI through final study visit on study Day 203
measure: Adverse events related to abnormal clinical safety laboratory parameter (serum creatinine concentration) values
timeFrame: Day of CHTI through final study visit on study Day 203
measure: Adverse events related to abnormal clinical safety laboratory parameter (serum alanine aminotransferase concentration) values
timeFrame: Day of CHTI through final study visit on study Day 203
Secondary outcomes:
measure: Fecal egg detection
timeFrame: Day of CHTI through study Day 182
measure: Fecal egg counts
timeFrame: Weeks 12 through 26 post-CHTI
measure: T. trichiura DNA in fecal samples
timeFrame: Weeks 12 through 26 post-CHTI
Other outcomes:
measure: Serum cytokine concentrations
timeFrame: Weeks 12 through 26 post-CHTI
measure: Cytokine concentrations of supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with T. trichiura antigen
timeFrame: Day of CHTI through final study visit on study Day 203
measure: Fecal microbiome
timeFrame: Day of CHTI through final study visit on study Day 203
Locations:
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
city: Bethesda
country: United States
facility: NIH Clinical Center
state: Maryland
Study officials:
References: