MET-2 Clinical Study for Recurrent Clostridium Difficile Infection (CDI)

Study Overview
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Brief Summary
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MET-2 clinical study is an Open label, single center, multiple dose pilot study of 19 patients. The study is designed to measure the resolution of diarrhea as well as the feasibility of administration and safety of MET-2 for the treatment of recurrent CDI in patients who have experienced at least two prior episodes of CDI and have developed recurrence after having completed standard-of care oral antibiotic therapy to treat CDI.

Detailed Description
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Microbial Ecosystem Therapeutics (MET) is a new treatment approach for debilitating recurrent Clostridium difficile infection that has been developed as an alternative to fecal transplantation. This treatment is not a drug or biologic, but is comprised of live microbes that normally reside in the human gut of a healthy individual.The product is a defined microbial community derived from healthy donor stool, referred to as Microbial Ecosystem Therapeutic-2 (MET-2). In this open label, single center, multiple dose pilot study of 19 patients will be recruited. Patients will be given an initial daily loading dose of MET-2 over 2 days followed by a maintenance dose of MET-2 over 8 days. Patients experiencing treatment failure after the first dose may be offered a second, higher loading dose of MET-2. Patients failing the second loading dose of MET-2 may be offered a higher dose of MET-2 via colonoscopy. The primary objective is clinical resolution of diarrhea with no CDI relapse at 30 days following the last dose of MET-2, i.e., absence of recurrence of diarrheal symptoms with laboratory-confirmed evidence of C. difficile 30 days after last dose of treatment. The secondary objectives are: i) Safety and tolerability, including adverse events of grade 2 or above; ii) Overall well-being including number of bowel movements and energy level, etc. as based on standardized IBS questionnaire; iii) Presence of MET-2 bacteria in stool at 30 days, based on DNA sequencing; and, iv) Mortality, at end of follow up period - mortality attributable to CDI will also be determined, by performing a detailed clinical chart review on any patient who expires during the follow up period.

Official Title
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A Phase I, Open-Label, Single-Centre Study of the Safety and Efficacy of MET-2 in Patients With Recurrent Clostridium Difficile Infection (CDI)

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Drug: MET-2
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years old. Able to provide informed consent, or have a caregiver able to provide consent Meets the definition of non-severe recurrent CDI (see Section 2.1, above) AND Has had a positive stool test for C. difficile within 60 days of enrolment Able to undergo colonoscopy and enemas Not pregnant Willing to participate in follow up as part of the study In addition, the patient must agree to undergo stool testing and blood screening tests that are part of the study, including hepatitis and HIV testing Exclusion Criteria: Life expectancy < 6 months Evidence of severe CDI ((neutropenia (ANC<1000) or WBC>30, creatinine >2X baseline, presence of toxic megacolon or intestinal perforation, admission to ICU) History of chronic diarrhea Need for regular use of agents that affect GI motility (narcotics such as codeine or morphine, agents such as loperamide or metoclopramide) Use of antibiotics for another infection (other than CDI) Colostomy Elective surgery that will require preoperative antibiotics planned within 6 months of enrolment Pregnant or planning to get pregnant in the next 6 months Unable to tolerate MET-2 for any reason Any condition for which colonoscopy or enema may be contraindicated (e.g., neutropenia, thrombocytopenia, bleeding disorders, severe colitis, etc) Any condition for which, in the opinion of the investigator, the patient should be excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MET-2 Capsules<br>Patients will be on vancomycin to control symptoms up until the time of the treatment. Initial Loading Dose: Patients will be given an initial daily loading dose of 5 g MET-2 over 2 days followed by a maintenance dose of 1.5 g over 8 days. Patients who do not experience treatment failure between Day 14 and Day 40 will be monitored until Day 130. Second Loading Dose: Patients experiencing treatment failure after the first dose may be offered a second, higher loading dose 10 g of MET-2 in the form of 20 MET-2 capsules per day for two days, there will not be additional daily dosing beyond the first 10 days. Colonoscopy: Patients failing the second loading dose of MET-2 may be offered 15 g of MET-2, equivalent to a 30 MET-2 capsule loading dose by weight, via colonoscopy.. All patients will be followed up for 120 days after the last treatment has been received. | Drug: MET-2<br>* Microbial Ecosystem Therapeutics (MET) is a new treatment approach for debilitating recurrent Clostridium difficile infection that has been developed as an alternative to fecal transplantation.<br>Drug: Vancomycin<br>* Patients will be on vancomycin to control symptoms up until the time of the treatment. Patient must hold their p.o. vancomycin for 24 hours prior to receiving the first dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate clinical resolution of diarrhea with no CDI relapse, | To demonstrate clinical resolution of diarrhea with no CDI relapse at 30 days following the last dose of MET-2, the subject will undergo full physical examination including Blood Pressure, Heart rate and body temperature measurement. A blood test will be conducted with chemistry panel, and CBC with differential. Stool test and culture will also be conducted to measure the presence of C.difficile and DNA sequencing will determine the presence of MET-2 bacteria in the stool. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (safety and tolerability) | safety and tolerability, including adverse events of grade 2 or above | 3 months | 
| number of bowel movements (overall well-being) | overall well-being including number of bowel movements, etc as based on standardized IBS questionnaire | 3 months | 
| Presence of MET-2 bacteria | Presence of MET-2 bacteria in stool at 30 days, based on DNA sequencing | 30 days | 
| mortality | Mortality, at end of follow up period - mortality attributable to CDI will also be determined, by performing a detailed clinical chart review on any patient who expires during the follow up period. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDI, recurrent infection, MET-2, C. difficile