Study to Assess Safety, Tolerability and Efficacy of Incremental Doses of MGB-BP-3 in Patients With CDAD

Study Overview
=================
Brief Summary
-----------------
The objective of this Phase IIa study is to assess the safety, tolerability, and efficacy of incremental doses of MGB-BP-3 in patients with Clostridium difficile-associated diarrhea (CDAD).

Detailed Description
-----------------
This is an exploratory, Phase IIa, open-label study assessing the safety, tolerability, and efficacy of incremental doses of MGB-BP-3 with 3 sequential groups of 10 patients with CDAD. Patients will be administered an oral dose of MGB-BP-3 for 10 days (Day 1 to Day 10). At the end of the treatment period, patients will be followed for up to 8 weeks to assess the incidence of disease recurrence.

Official Title
-----------------
An Exploratory, Open Labelled, Phase IIa Study to Assess Safety, Tolerability and Efficacy of Incremental Doses of MGB-BP-3 in Patients With Clostridium Difficile-associated Diarrhea (CDAD)

Conditions
-----------------
Clostridium Difficile Infection

Intervention / Treatment
-----------------
* Drug: MGB-BP-3


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: Age 18 years or older of any gender. Inpatients and/or outpatients who are able to attend all scheduled visits. Patients with the first episode or the first recurrence of mild or moderate CDAD. Confirmed diagnosis of mild or moderate CDAD as defined by the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America guidelines. Main Exclusion Criteria: Patients with severe complicated CDAD (including hypotension or shock, ileus, megacolon, pseudomembranous colitis). A white blood cell count higher than 15,000 cells/mL. A serum creatinine level greater than or equal to 1.5 times ULN. Elevated liver enzymes alanine aminotransferase and aspartate aminotransferase greater than ULN. Inflammatory bowel disease (ulcerative colitis or Crohn's disease), microscopic colitis, or irritable bowel syndrome with chronic diarrhea. Any other non-C difficile diarrhea. Received treatment with a fecal transplant within 7 days and/or is anticipated to receive a fecal transplant during the study. Major gastrointestinal surgery (ie, significant bowel resection) within 3 months of enrollment (does not include appendectomy or cholecystectomy). Received laxatives within the previous 48 hours. Pregnant or lactating women. Prior (within 180 days of Screening) or current use of anti-toxin antibodies. Have received a vaccine against C difficile. Any condition for which, in the opinion of the investigator, the treatment may pose a health risk to the patient.

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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is an open-label study with 3 sequential groups of 10 patients with CDAD with a staggered start.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1: 125mg b.i.d. for 10 days<br>Patients will be administered an oral dose of 125mg b.i.d. MGB-BP-3 for 10 days (Day 1 to Day 10). | Drug: MGB-BP-3<br>* MGB-BP-3<br>* Other names: No other names - not applicable;|
| Active Comparator: Group 2: 250mg b.i.d. for 10 days<br>Patients will be administered an oral dose of 250mg b.i.d. MGB-BP-3 for 10 days (Day 1 to Day 10). | Drug: MGB-BP-3<br>* MGB-BP-3<br>* Other names: No other names - not applicable;|
| Active Comparator: Group 3: 500mg b.i.d. for 10 days<br>Patients will be administered an oral dose of 500mg b.i.d. MGB-BP-3 for 10 days (Day 1 to Day 10). | Drug: MGB-BP-3<br>* MGB-BP-3<br>* Other names: No other names - not applicable;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events assessed by the Investigator, as per CTCAE v.5.0. | Incidence of treatment emergent adverse events (Safety and Tolerability of up to 3 incremental doses of MGB-BP-3 in patients with CDAD). | 40 days | 
| Initial cure rate at 12 days post initiation of therapy. | Initial clinical cure is defined as resolution of diarrhea (<3 bowel movements with unformed stools within 24 hours [Type 5, 6, or 7 bowel movement on the Bristol Stool Chart] for patients for 2 consecutive days), maintained for the subsequent duration of therapy (1 day of exacerbation and then return to the resolved state is acceptable), with no further requirement for CDAD therapy, assessed by EOT and sustained for 2 days after the end of the 10-day initial treatment course. | 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CDAD Recurrence | Recurrence of CDAD within 4 weeks (8 weeks optional) post end of treatment. | Up to 8 weeks | 
| Peak plasma concentration (Cmax). | Days 1, 5 and 10. | 10 days | 
| Time to peak plasma concentration (Tmax). | Days 1, 5 and 10. | 10 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Efficacy, Clostridium difficile, CDAD, MGB-BP-3, Novel anti-infective, Tolerability, Safety, Phase IIa