A Safety Trial to Evaluate an Orally Ingested Yeast Modified to Express a Tetra-specific Anti-toxin for Clostridioides Difficile

What this study involves

The registry says this study is recruiting. Individual locations may have different availability.

Study type

Interventional

Phase

Phase 1

Age range

18 years - 75 years

Sex eligible

All sexes

Healthy volunteers

Accepted

Participants

56 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

This is a Phase 1, first-in-human, double-blind, placebo-controlled, adaptive-design, single-site study, involving dose exploration cohorts.

During dose escalation, up to 4 cohorts, each consisting of up to 14 healthy adult (18-75 years, inclusive) study participants, will be randomly allocated to receive either FZ002 (n=12) or placebo (n=2). Dose escalation is designed to begin with the first cohort (Cohort 1) evaluating the lowest proposed dose of study product (1 capsules taken daily for 28 consecutive days). The first 3 participants will serve as sentinels and randomized in 2:1 ratio (FZ200: placebo). After review of the sentinel participants' data by the PSRT, the remaining participants (n=11) in the cohort will be randomly allocated in a 10:1 ratio (FZ002: placebo).

The primary objective is to evaluate safety and clinical tolerability of oral doses of FZ002 or placebo when taken for up to 28 days.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

Inclusion Criteria:

To be eligible to participate in this trial, an individual must meet all of the following criteria:

1. Provides written informed consent prior to the initiation of any trial procedures.
2. Is able to understand and agrees to comply with all planned trial procedures and be available for all study visits, including:

1. Receiving 28 days of blinded oral study product
2. Providing blood and self-collected stool samples
3. Is a non-pregnant individual, aged 18-75 years, inclusive, at the time of enrollment.
4. Has no more than 1 single Grade 1 screening laboratory abnormality that is not clinically significant. If the participant has more than 1 Grade 1 abnormality, it must be approved by the Division of Microbiology and Infectious Diseases \[DMID\] Medical Monitor (MM).
5. Participants of childbearing potential: use of adequate contraception for at least 4 weeks prior to enrollment and agreement to use such a method during trial participation and for an additional 4 weeks after the last dose of blinded study product. Note: Definitions of participants of childbearing potential and adequate contraception are provided in Section 13.1.
6. Agrees to refrain from ingestion of probiotics\* or fermented foods\*\* from 7 days prior to study product administration, while on blinded study product, and through Day 36 (Visit 7).

\*E.g., probiotic nutritional Lactobacillus or Bifidobacterium supplements, yogurt, kefir, any "live and active culture" nutritional product, etc.

\*\*E.g., kombucha, fermented pickled vegetables, etc.
7. Has good health by medical history, vital signs, physical examination, and concomitant medication review\*. Participants should be stable based on their condition over the last 3 months prior to enrollment.

\*As defined by not requiring a change in therapy (including dose or frequency) or medical care for worsening disease for at least 3 months prior to enrollment. Vital signs must not meet Grade 1 or higher.
8. Not using medications daily that may affect gut motility, gastric acidity, or baseline gut function\* within 3 months of enrollment and through Day 36 (Visit 7).

\*E.g., proton pump inhibitors, opioids, anti-diarrheal agents, anti-constipation agents, daily Over-the-counter \[OTC\] "heartburn" relief medications.
9. Not using glucagon-like peptide-1 (GLP-1) receptor agonists within 6 weeks of enrollment.
10. Any elective surgery (including dental) that required preoperative or postoperative antibiotics must have been completed at least 3 months prior to enrollment.
11. No history of Clostridioides difficile infection \[CDI\] (suspected or proven), no recent hospital admissions (within 3 years), and no receipt of systemic antibiotics known to increase risk of CDI\* (within 6 months).

\*Systemic antibiotics that are known to increase the risk of CDI include lincosamides (e.g., clindamycin), monobactams (e.g., aztreonam), extended-spectrum penicillin combinations with beta-lactamase inhibitors (e.g., piperacillin-tazobactam), carbapenems (e.g., imipenem, meropenem, ertapenem), third generation or higher cephalosporins, and fluoroquinolones. Common oral antibiotics that would be allowable or are not known to significantly increase risk of CDI include amoxicillin, azithromycin, cephalexin, doxycycline, metronidazole, and trimethoprim/sulfamethoxazole.
12. No history of other enteric infections or diarrheal illness within 3 months of enrollment.

Exclusion Criteria:

1. Dwells in a long-term care or skilled nursing facility (living independently with limited nursing care is allowable).
2. Known to be pregnant or has a positive pregnancy test at screening or enrollment.
3. Currently breastfeeding a child.
4. Known to have a yeast allergy or significant hypersensitivity to any components of the study product; including S. boulardii (or any S. boulardii-based nutritional supplement), hydroxypropyl methylcellulose, and Microcrystalline cellulose \[MCC\].

Hydroxypropyl methylcellulose is the major component of the capsule shell and MCC is the placebo component.
5. Known to have significant hypersensitivity to a first-line antifungal therapy (i.e., fluconazole or amphotericin B) against Saccharomyces.
6. Known to be immunocompromised or have known or suspected congenital or acquired immunodeficiency, as determined by the investigator.
7. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 3 years of enrollment.
8. Receipt of chronic (\>/=14 days) immunosuppressive corticosteroids at a dose of \>/=20 mg prednisone daily or prednisone equivalent within 30 days of enrollment, including oral, parenteral, or high dose inhaled\* corticosteroids.

\*High-dose inhaled corticosteroid is defined as \>800 mcg/day of beclomethasone dipropionate chlorofluorocarbon compounds \[CFC\] or equivalent. Intra-articular, intranasal, and topical steroids are allowable.
9. Active malignancy or history of malignancy in the past 3 years (non-melanoma, excised, cured skin cancers are allowed).
10. History of or testing positive for human immunodeficiency virus (HIV), hepatitis B, or active hepatitis C at screening (positive hepatitis C antibody and detectable hepatitis C virus RNA).
11. Anticipated or current receipt of kidney dialysis treatment.
12. Concurrent, acutely life-threatening disease or condition, or any unstable medical history, as determined by the investigator.
13. Significant chronic gastrointestinal \[GI\] condition(s) or disease\*.

\*Includes diagnosis of inflammatory bowel disease or active Rome IV irritable bowel syndrome, poorly controlled Celiac disease, active gastroparesis, toxic megacolon, colostomy, intestinal resection (except uncomplicated appendectomy), ileus, short gut syndrome, or recent (within 6 months of enrollment) diverticular bleeding requiring surgical intervention or transfusion.
14. Recent (within 6 months of enrollment) history of difficulty with swallowing food, liquids, or pills.
15. Prosthetic heart valve or indwelling foreign structure within vascular supply (e.g., no central line or indwelling catheter) or known to have moderate to severe valvular disease.
16. History of alcohol abuse or drug addiction within 5 years of enrollment or that might interfere with the ability to comply with trial procedures.
17. Diagnosis of schizophrenia, bipolar disease, or other significant psychiatric disease in the opinion of the investigator that may interfere with or pose a problem with compliance with the study or the welfare of the participant.
18. Presence of mild, acute, or self-limited condition, such as fever or cough or other symptoms of upper respiratory tract infection within 7 days prior to planned randomization.
19. Any chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion or participant safety.
20. Identified as a study site or contract research organization employee or family member who is involved in the protocol and may have direct access to trial-related data.
21. Participating in another clinical trial investigating a vaccine, drug, medical device, or medical procedure within 4 weeks of enrollment through the last visit of the study.

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment

Random assignment

Masking

Triple masked

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Secondary measures

Research locations (1)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

1 locations

Study team and timeline

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Study start

Oct 29, 2026 Estimated

Primary completion

Aug 22, 2028 Estimated

Study completion

Sep 22, 2028 Estimated

First posted

Jun 16, 2026 Actual

Last updated

Nov 10, 2026 Actual

Official study contacts