Safety and Tolerability of FMT Capsules in Healthy Volunteers

Study Overview
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Brief Summary
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This is a two-part, randomized, double-blind, placebo-controlled, single center study to investigate the safety and tolerability of XBI-302 administered orally in healthy volunteers. The hypothesis of this study is that XBI-302 is safe and well tolerated with the proposed dosing regimens.

Official Title
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Safety and Tolerability of Xbiome Gut Microbial Capsule XBI-302 in Healthy Volunteers

Conditions
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Acute-graft-versus-host Disease

Intervention / Treatment
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* Biological: XBI-302
* Biological: XBI-302 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to participate and sign the ICF. Healthy adults 18-55 years of age, male and female. For women of childbearing age, negative serum pregnancy test at Screening and negative serum pregnancy test confirmed at the admission to the Phase 1 unit. Female participants must not be pregnant, lactating, or actively trying to become pregnant. Participants who are premenopausal and of childbearing potential must have two negative pregnancy tests (serum) and both female and male participants must use medically acceptable and effective contraceptive methods during the study period, including: Having a male partner who is sterile prior to the female participant's entry into the study and is the sole sexual partner for that female participant Use of double-barrier methods of contraception; condoms with the use of caps (with spermicide) and intra-uterine devices are acceptable True abstinence, when this is in line with the preferred and usual lifestyle of the participant (Note: period abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) Clinical laboratory test values (hematology, blood chemistry, routine stool test, urinalysis, etc.) are in the normal ranges or although it was outside the normal limits, the researchers determined that the participant will still be eligible within the screening period. Participants have a body mass index (BMI) between 18 and 30 kilogram per meter square (kg/m2) inclusive, and a body weight of at least 45 kilograms (kg). Exclusion Criteria: History of cardiovascular disease, immune system disease, malignant disease such as cancer, nervous system disease, hematological disease, endocrinological disease, and/or any other diseases that in the opinion of the investigator could impact assessments of safety or the gut microbiome. Significant past medical history of GI conditions including inflammatory bowel disease, irritable bowel syndrome, celiac disease, history of GI malignancy or polyposis, C. difficile infection in past year. GI symptoms that occur more than four times a month including acid reflux, nausea, vomiting, diarrhea, abdominal pain or cramps, abdominal distension, bloating, constipation. Used oral antibiotics within 4 weeks prior to the first FMT dosing. HIV infection and/or HBV/HCV infection. Active tuberculosis and undergoing treatment. History of mental illness, drug or alcohol abuse and/or any other behavioral issues that may impact study compliance. Lactating women or participants who plan to become pregnant or conceive within half a year. History of severe hypersensitivity (may cause difficulty in breathing). Alcohol breathalyzer test positive, urine drug screening test positive, and/or smoker. Participated in any other clinical trials within 3 months of first dose. Participants with history of bowel or gastrointestinal surgery. Participants who are immunosuppressed or immunocompromised, either by genetic, acquired or secondary to medication. Participants who are experiencing symptoms associated with COVID-19 (including but not limited to cough, fever, shortness of breath, nausea, diarrhea, anhedonia, anosmia, ageusia or severe fatigue).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 XBI-302<br>40 XBI-302 capsules in 1 day | Biological: XBI-302<br>* Fecal Microbiota Transplantation Capsules<br>|
| Placebo Comparator: Cohort 1 Placebo<br>40 placebo capsules in 1 day | Biological: XBI-302 Placebo<br>* XBI-302 Placebo<br>|
| Experimental: Cohort 2 XBI-302<br>80 XBI-302 capsules over 2 days | Biological: XBI-302<br>* Fecal Microbiota Transplantation Capsules<br>|
| Placebo Comparator: Cohort 2 Placebo<br>80 placebo capsules over 2 days | Biological: XBI-302 Placebo<br>* XBI-302 Placebo<br>|
| Experimental: Cohort 3 XBI-302<br>40 XBI-302 capsules per day, once a week for 4 weeks. | Biological: XBI-302<br>* Fecal Microbiota Transplantation Capsules<br>|
| Placebo Comparator: Cohort 3 Placebo<br>40 placebo capsules per day, once a week for 4 weeks. | Biological: XBI-302 Placebo<br>* XBI-302 Placebo<br>|
| Experimental: Cohort 4 XBI-302<br>80 XBI-302 capsules over 2 days, once a week for 4 weeks. | Biological: XBI-302<br>* Fecal Microbiota Transplantation Capsules<br>|
| Placebo Comparator: Cohort 4 Placebo<br>80 placebo capsules over 2 days, once a week for 4 weeks. | Biological: XBI-302 Placebo<br>* XBI-302 Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of all AEs and SAEs | The incidence and severity of all AEs and SAEs that are determined to be related to XBI-302 through Day 28. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of all AEs and SAEs | The incidence of all AEs and SAEs through Day 28 and Week 12. | Day 28 and Week 12 | 
| Change in laboratory data of pre- and post-intervention as a measure of safety. | Compare changes laboratory data via hematology, blood chemistry, urinalysis, and routine stool testing before and after using FMT capsules. | Baseline, Weeks 1, 2, 3, 4, and 12 (if applicable for the arm) | 
| Change in functions of all organ systems via standard complete physical examinations. | Change in functions of all organ systems via standard complete physical examinations. | Baseline, Weeks 1, 2, 3, 4, and 12 (if applicable for the arm) | 
| Change in functions of heart, lungs, abdomen and other organ that involve the gastrointestinal tract and digestive system via targeted physical examinations. | Change in functions of heart, lungs, abdomen and other organ that involve the gastrointestinal tract and digestive system via targeted physical examinations. | Baseline, Weeks 1, 2, 3, 4, and 12 (if applicable for the arm) | 
| Change in vital signs in ear temperature, pulse, respirations, and blood pressure as a measure of safety. | Change in vital signs in ear temperature, pulse, respirations, and blood pressure as a measure of safety. | Baseline, Weeks 1, 2, 3, 4, and 12 (if applicable for the arm) | 
| The incidence of gastrointestinal AEs | Compare the incidence of gastrointestinal AEs on the dosing day(s) between treatment groups. | Weeks 1, 2, 3, and 4 (if applicable for the arm) | 
| The level of difficulty of swallowing FMT capsules as a measure of tolerability. | Estimate degree of difficulty of swallowing FMT capsules via daily diary cards by selecting easy, ok, hard (must rest frequently to complete all capsules), or very hard (stuck to my throat all the time, took a long time to finish all capsules). | Weeks 1, 2, 3, and 4 (if applicable for the arm) | 
| The subjective experience of the taste acceptance as a measure of tolerability. | Estimate degree of taste acceptance of FMT capsules via daily diary cards by selecting none, ok, a strange taste, or strong taste that makes me nauseous. | Weeks 1, 2, 3, and 4 (if applicable for the arm) | 
| The gut microbiome profile | Compare the gut microbiome profile before and after the transplantation between treatment groups. | Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, and 12 (if applicable for the arm) | 
| The gut microbiome profile | Compare the gut microbiome profile before and after the transplantation between donors and participants. | Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, and 12 (if applicable for the arm) | 
| The colonization of microbiota from donor | Compare the effects of diet and lifestyle on the colonization of microbiota from donor before and after FMT. | Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, and 12 (if applicable for the arm) |