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

Overview

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

Interventions

• Biological Trichuris trichiura Egg Inoculum
  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 eg

Primary outcome measures

• Solicited adverse events, graded by severity [Time frame: Day of CHTI through study Day 182]
• Serious Adverse Events [Time frame: Day of CHTI through final study visit on study Day 203]
• Unsolicited adverse events [Time frame: Day of CHTI through study Day 182]
• New-onset chronic medical conditions [Time frame: Day of CHTI through final study visit on study Day 203]
• Adverse Events of Special Interest [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 [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 [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 [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 [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 [Time frame: Day of CHTI through final study visit on study Day 203]

Secondary outcome measures (3)

• Fecal egg detection [Time frame: Day of CHTI through study Day 182]
• Fecal egg counts [Time frame: Weeks 12 through 26 post-CHTI]
• T. trichiura DNA in fecal samples [Time frame: Weeks 12 through 26 post-CHTI]

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.
• Ability to sign and understand 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.
• Inability to speak English.
• Current/planned simultaneous participation in another study of an investigational agent or device for the duration of their study participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• George Washington University Medical Faculty Associates — Washington D.C.
• NIH Clinical Center — Bethesda

Identifiers

NCT: NCT05706116 · CHTI-01-21

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗