Clostridium Difficile InfectionPhase 1NCT02865616
MET-2 Clinical Study for Recurrent Clostridium Difficile Infection (CDI)
A Phase 1 study testing MET-2 and Vancomycin in people with Clostridium Difficile Infection, run by NuBiyota at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile Infection
- What is being tested?
- MET-2 and Vancomycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteCanada
- Study dates
- 27 Oct 2017to 17 Mar 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Clostridium Difficile Infection
- Being tested
- MET-2, Vancomycin
- Keywords
- CDI, recurrent infection, MET-2, C. difficile
- Medical subject headings
- Clostridium Infections, Reinfection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MET-2Drug
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.
VancomycinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| MET-2 Capsules | Experimental | 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. Receives: Drug: MET-2; Drug: Vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days
Secondary outcomes (4)
Incidence of adverse events (safety and tolerability)
safety and tolerability, including adverse events of grade 2 or above
Measured: 3 months
number of bowel movements (overall well-being)
overall well-being including number of bowel movements, etc as based on standardized IBS questionnaire
Measured: 3 months
Presence of MET-2 bacteria
Presence of MET-2 bacteria in stool at 30 days, based on DNA sequencing
Measured: 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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2016 (estimated)
- Study start27 Oct 2017
- Primary completion17 Mar 2020
- Study completion17 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridium Difficile InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- NuBiyota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dina Kao, MD, Principal investigator, University of Alberta, Edmonton Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02865616
- Sponsor's protocol ID
- MET-2-101
- Status last verified
- Aug 2020
- First submitted
- 4 Aug 2016
- Last updated
- 11 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 33631102
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02865616
- Acronym / sponsor ID
- MET-2-101
- Conditions
- Clostridium Difficile Infection
- Keywords
- CDI, recurrent infection, MET-2, C. difficile
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- NuBiyotaUniversity, hospital or other
- Study start
- 27 Oct 2017 (actual)
- Primary completion
- 17 Mar 2020 (actual)
- Study completion
- 17 Mar 2020 (actual)
- First posted
- 12 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MET-2 Capsules | Experimental | Drug: MET-2, Drug: VancomycinPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- ≥ 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MET-2Microbial Ecosystem Therapeutics (MET) is a new treatment approach for debilitating recurrent Clostridium difficile infection that has been developed as an alternative to fecal transplantation. | Drug | MET-2 Capsules |
| VancomycinPatients 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. | Drug | MET-2 Capsules |
Primary outcome
To demonstrate clinical resolution of diarrhea with no CDI relapse,
Time frame: 30 days
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.
4 secondary outcomes
Incidence of adverse events (safety and tolerability)
Time frame: 3 months
number of bowel movements (overall well-being)
Time frame: 3 months
Presence of MET-2 bacteria
Time frame: 30 days
mortality
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- Derived from this study: PubMed 33631102Kao 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dina Kao, MD principal investigator
University of Alberta, Edmonton Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MET-2 and Vancomycin in people with Clostridium Difficile Infection, run by NuBiyota at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To demonstrate clinical resolution of diarrhea with no CDI relapse, (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02865616, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2020.