Clinical trial NCT02865616: MET-2 Clinical Study for Recurrent Clostridium Difficile Infection (CDI)
Official title: A Phase I, Open-Label, Single-Centre Study of the Safety and Efficacy of MET-2 in Patients With Recurrent Clostridium Difficile Infection (CDI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Clostridium Difficile Infection
Keywords: CDI
recurrent infection
MET-2
C. difficile
Lead sponsor: NuBiyota
Sponsor class: OTHER
First posted: 2016-08-12
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. ≥ 18 years old.
2. Able to provide informed consent, or have a caregiver able to provide consent
3. Meets the definition of non-severe recurrent CDI (see Section 2.1, above) AND
4. Has had a positive stool test for C. difficile within 60 days of enrolment
5. Able to undergo colonoscopy and enemas
6. Not pregnant
7. 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:

1. Life expectancy \< 6 months
2. Evidence of severe CDI ((neutropenia (ANC\<1000) or WBC\>30, creatinine \>2X baseline, presence of toxic megacolon or intestinal perforation, admission to ICU)
3. History of chronic diarrhea
4. Need for regular use of agents that affect GI motility (narcotics such as codeine or morphine, agents such as loperamide or metoclopramide)
5. Use of antibiotics for another infection (other than CDI)
6. Colostomy
7. Elective surgery that will require preoperative antibiotics planned within 6 months of enrolment
8. Pregnant or planning to get pregnant in the next 6 months
9. Unable to tolerate MET-2 for any reason
10. Any condition for which colonoscopy or enema may be contraindicated (e.g., neutropenia, thrombocytopenia, bleeding disorders, severe colitis, etc)
11. Any condition for which, in the opinion of the investigator, the patient should be excluded from the study.

Primary outcomes:
measure: To demonstrate clinical resolution of diarrhea with no CDI relapse,
timeFrame: 30 days
Secondary outcomes:
measure: Incidence of adverse events (safety and tolerability)
timeFrame: 3 months
measure: number of bowel movements (overall well-being)
timeFrame: 3 months
measure: Presence of MET-2 bacteria
timeFrame: 30 days
measure: mortality
timeFrame: 3 months
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: University of Alberta, Edmonton Alberta
name: Dina Kao, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kao D, Wong K, Franz R, Cochrane K, Sherriff K, Chui L, Lloyd C, Roach B, Bai AD, Petrof EO, Allen-Vercoe E. The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial. Lancet Gastroenterol Hepatol. 2021 Apr;6(4):282-291. doi: 10.1016/S2468-1253(21)00007-8. Epub 2021 Feb 23.