A Study of Safety of PBCLN-003 Following Antibiotic Therapy in Subjects With C.Difficile-associated Diarrhea

Study Overview
=================
Brief Summary
-----------------
This Phase I double blind, randomized clinical study to evaluate the safety of human milk oligosaccharides (HMO) is designed to assess the safety and dosage ranging of PBCLN-003 in adults with Clostridium difficile-associated diarrhea (CDAD). Within 3 dose cohort, subjects will be randomized in a 3:1 ratio to receive PBCLN-003 or placebo.

Official Title
-----------------
A Phase 1 Double Blind, Randomized Clinical Study to Evaluate the Safety of Human Milk Oligosaccharides Following Antibiotic Therapy in Subjects With C. Difficile-associated Diarrhea

Conditions
-----------------
Clostridium Difficile Diarrhea

Intervention / Treatment
-----------------
* Drug: PBCLN-003
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Enrollment episode of CDAD diagnosed based on > 3 loose stools per day and detection of CD toxin by nucleic acid amplification tests (NAAT), EIA or GDH Mild to moderate CDAD during enrollment episode (per Society of Hospital Epidemiologists of America (SHEA)/lnfectious Disease Society of America(ISDA) criteria) Current therapy with standard of care antibiotics for recurrent CDAD(vancomycin, metronidazole, fidaxomicin) BMI > 18.5 and < 40 Age 18 years or older Agreement to adhere to the study protocol Informed consent is obtained Women who are capable of bearing children must have a negative pregnancy test at the time of screening Female subjects of childbearing potential must use birth control (defined as oral or injectable contraceptives, intrauterine devices, surgical sterilization or a combination of a condom and spermicide) during the study period and for up to 8 weeks after the first drug of study. Exclusion Criteria: Severe CDAD during enrollment episode (per SHEA/ISDA criteria) characterized as follows: History of five (5) or more recurrences of CDAD within the past 12 months prior to potential study enrollment History of fecal microbiome transplant or other microbiome directed experimental intervention for CDAD History (ever) of CD complicating inflammatory bowel disease (Crohn's disease, ulcerative colitis), or history of bowel resection surgery (other than uncomplicated appendectomy) or history of other infectious diarrhea or diarrhea of unknown etiology since the initial episode of CDAD Clinically immunocompromised due to any primary immune or autoimmune deficiency, as a result of chronic disease, cancer or medication used to treat these diseases Initiating a new diet or weight loss amounting to 10% within two weeks prior to date of study entry Enrolled in another clinical study for the therapy of CDAD or affecting nutritional management during the study period Enrolled or has been enrolled in another experimental (IND) study within two weeks prior to date of study entry Is pregnant or lactating History of swallowing difficulties, including dysphagia or odynophagia for liquids or solids Use of any Probiotics (any formulation) within the two weeks prior to date of study entry New, or a change in the consumption of the following prescription medications or over-the-counter (OTC) medications within two weeks prior to date of study entry: Proton pump inhibitors (for example: Prilosec®, Nexium®) Histamine-2 receptor antagonists (for example: Zantac®, Pepcid®) Consumption of the following prescription medications during the current enrollment episode: • Bezlotuxamab/Zinplava®

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>PBCLN-003, daily in 3 divided oral doses for 7 days, 2 ascending dose cohorts | Drug: PBCLN-003<br>* Investigational drug<br>|
| Placebo Comparator: Placebo<br>Placebo, daily in 3 divided oral doses for 7 days, 2 ascending dose cohorts | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of Adverse Events in a dose escalation study of PBCLN-003 | Comparison of adverse event reporting and grading results between groups using physical exams, safety related blood tests, and urinalysis, adverse event reports, and subject complaint logs. | Up to 8 Weeks |