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

NCT07649096 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 24-003475N93022D00018
• Study Type: interventional
• Target: 86
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 1, first-in-human, double-blind, placebo-controlled, adaptive-design, single-site study, involving dose exploration cohorts. During Part A, up to 4 cohorts, each consisting of approximately 14 healthy adult study participants, will be randomly allocated to receive either FZ002 or placebo. Part A is designed to begin with Cohort 1 evaluating the highest proposed dose of study product. This is intended to represent the "ceiling" (highest level) of the ranges of doses to be evaluated in the study. In the event of a safety or tolerability concern in Cohort 1, a dose de-escalation will be evaluated in Cohorts 2-4 until a safe and well-tolerated dose is identified. If no safety or tolerability concerns are identified at the completion of a cohort, the study will proceed to Part B with the approval of the independent Safety Monitoring Committee (SMC). This adaptive design allows for the progression of the study from Part A to Part B without necessarily progressing through all 4 cohorts in Part A if there is a lack of safety or tolerability concerns. During Part B, an initial 'sentinel' Cohort 5 "some-risk" adult study participants will be randomly allocated to receive a single daily dose of FZ002 or placebo for 28 consecutive days. This is intended to represent the "floor" (lowest level) of doses to be evaluated in the study. A Protocol Safety Review Team (PSRT) will review the available safety data from the first 7 days of Cohort 5. If there is a lack of safety or tolerability concerns over the first 7-days of dosing for Cohort 5, then Cohort 6 will be opened for enrollment. Cohort 6 "some-risk" adult study participants will evaluate the "floor" and "ceiling" dose of FZ002 versus 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.

Conditions

Clostridium Difficile Infection

Keywords

Clostridioides difficile; Clostridium difficile; Phase 1; Probiotic Yeast; Tetra-specific Anti-toxin

Outcome Measures

Primary Outcomes (4)

• Occurrence of serious adverse events (SAEs)

  Through Day 208

• Occurrence of solicited adverse events (AEs)

  Solicited AEs will include headache, fever, nausea, abdominal pain, diarrhea, malaise, constipation, fatigue, and vomiting. Oral temperatures will be measured daily.

  Through Day 35

• Occurrence of unsolicited AEs

  Through Day 57

• The occurrence of any positive yeast blood culture for Saccharomyces

  Days 8 and 29

Secondary Outcomes (1)

• The occurrence of abnormalities in clinical safety laboratory parameters based on change from baseline

  Days 8 and 29

Study Arms (14)

Part A Cohort 1 Arm FZ002

EXPERIMENTAL

Healthy adults administered 4 capsules of FZ002 orally QH12 for 28 days. N=12

Biological: FZ002

Part A Cohort 1 Arm Placebo

PLACEBO COMPARATOR

Healthy adults administered 4 capsules of placebo orally QH12 for 28 days. N=2

Other: Placebo for FZ002

Part A Cohort 2 Arm FZ002

EXPERIMENTAL

Healthy adults administered 2 capsules of FZ002 orally QH12 for 28 days. N=12

Biological: FZ002

Part A Cohort 2 Arm Placebo

PLACEBO COMPARATOR

Healthy adults administered 2 capsules of placebo orally QH12 for 28 days. N=2

Other: Placebo for FZ002

Part A Cohort 3 Arm FZ002

EXPERIMENTAL

Healthy adults administered 1 capsule of FZ002 orally QH12 for 28 days. N=12

Biological: FZ002

Part A Cohort 3 Arm Placebo

PLACEBO COMPARATOR

Healthy adults administered 1 capsule of placebo orally QH12 for 28 days. N=2

Other: Placebo for FZ002

Part A Cohort 4 Arm FZ002

EXPERIMENTAL

Healthy adults administered with 1 capsule of FZ002 orally once daily for 28 days. N=12

Biological: FZ002

Part A Cohort 4 Arm Placebo

PLACEBO COMPARATOR

Healthy adults administered with 1 capsule of placebo orally once daily for 28 days. N=2

Other: Placebo for FZ002

Part B Cohort 5 Arm FZ002

EXPERIMENTAL

"some-risk" adults administered with 1 capsule of FZ002 orally once daily for 28 days. N=4

Biological: FZ002

Part B Cohort 5 Arm Placebo

PLACEBO COMPARATOR

"some-risk" adults administered with 1 capsule of placebo orally once daily for 28 days. N=1

Other: Placebo for FZ002

Part B Cohort 6 Group 1 Arm FZ002

EXPERIMENTAL

"some-risk" adults administered with 4 capsules of FZ002 orally QH12 for 28 days. N=12

Biological: FZ002

Part B Cohort 6 Group 1 Arm Placebo

PLACEBO COMPARATOR

"some-risk" adults administered with 4 capsules of placebo orally QH12 for 28 days. N=3

Other: Placebo for FZ002

Part B Cohort 6 Group 2 Arm FZ002

EXPERIMENTAL

"some-risk" adults administered with 1 capsule of FZ002 orally once daily for 28 days. N=8

Biological: FZ002

Part B Cohort 6 Group 2 Arm Placebo

PLACEBO COMPARATOR

"some-risk" adults administered with 1 capsule of placebo orally once daily for 28 days. N=2

Other: Placebo for FZ002

Interventions

FZ002 BIOLOGICAL

A recombinant live biotherapeutic product (rLBP) for oral administration, bioengineered from the parental S. boulardii (Sb) strain to constitutively produce ABAB, an anti-toxin against TcdA and TcdB of CDiff, intended to reduce the risk of CDI recurrence.

Part A Cohort 1 Arm FZ002; Part A Cohort 2 Arm FZ002; Part A Cohort 3 Arm FZ002; Part A Cohort 4 Arm FZ002; Part B Cohort 5 Arm FZ002; Part B Cohort 6 Group 1 Arm FZ002; Part B Cohort 6 Group 2 Arm FZ002

Placebo for FZ002 OTHER

The placebo is a capsule filled with commercially sourced pharmaceutical-grade microcrystalline cellulose (MCC), an inert substance. No anticipated risk related to the study product.

Part A Cohort 1 Arm Placebo; Part A Cohort 2 Arm Placebo; Part A Cohort 3 Arm Placebo; Part A Cohort 4 Arm Placebo; Part B Cohort 5 Arm Placebo; Part B Cohort 6 Group 1 Arm Placebo; Part B Cohort 6 Group 2 Arm Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in Part A of this trial, an individual must meet all of the following criteria:
• Provides written informed consent prior to the initiation of any trial procedures.
• Is able to understand and agrees to comply with all planned trial procedures and be available for all study visits, including:
• Receiving 28 days of blinded oral study product
• Providing blood and self-collected stool samples
• Is a non-pregnant individual, aged 18-75 years, inclusive, at the time of enrollment.
• 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).
• 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.
• 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 6).
• \*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.
• 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.
• 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 6).
• \*E.g., proton pump inhibitors, opioids, anti-diarrheal agents, anti-constipation agents, daily Over-the-counter \[OTC\] "heartburn" relief medications.

You may not qualify if:

• Dwells in a long-term care or skilled nursing facility (living independently with limited nursing care is allowable).
• Known to be pregnant or has a positive pregnancy test at screening or enrollment.
• Currently breastfeeding a child.
• Known to have 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.
• Known to have significant hypersensitivity to a first-line antifungal therapy (i.e., fluconazole or amphotericin B) against Saccharomyces.
• Known to be immunocompromised or have known or suspected congenital or acquired immunodeficiency, as determined by the investigator.
• Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 3 years of enrollment.
• 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 CFC or equivalent. Intra-articular, intranasal, and topical steroids are allowable.
• Active malignancy or history of malignancy in the past 3 years (non-melanoma, excised, cured skin cancers are allowed).
• 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).
• Anticipated or current receipt of kidney dialysis treatment.
• Concurrent, acutely life-threatening disease or condition, or any unstable medical history, as determined by the investigator.
• Significant chronic gastrointestinal \[GI\] condition(s) or disease\*.

Sponsors & Collaborators

• Fzata, Inc: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): lead

MeSH Terms

Conditions

Clostridium Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Central Study Contacts

William B Smith

CONTACT

18663059100; william.smith@amr-clinical.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: June 16, 2026
• Study Start: July 27, 2026
• Primary Completion (Estimated): August 22, 2028
• Study Completion (Estimated): September 22, 2028
• Last Updated: July 31, 2026

Record last verified: 2026-06-04