MTC Versus FMT in for RCDI

Study Overview
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Brief Summary
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Investigating four different treatment of MTC or FMT

Detailed Description
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The purpose of this research study is to compare two different treatments for patients with recurrent Clostridiodies difficile infections: MTC01 vs fecal microbiota transplantation (FMT). FMT is the transfer of bacteria from a healthy donor's colon to a recipient's colon. To do this, stool from a healthy donor is blended with salt water and made into a liquid solution rich in bacteria. This solution is sprayed into the recipient's colon during a colonoscopy. This treatment is now considered standard medical care for recurrent Clostridioides difficile infections. One FMT dose contains the entire collection of microbes in a healthy donor and is made up of billions of microbes. Each dose of FMT is different from the next and it is unknown exactly what microbes are present in each dose.

Official Title
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Comparison of MTC01 vs FMT for the Treatment of Recurrent Clostridioides Difficile Infection

Conditions
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Clostridiodies Difficile Infections

Intervention / Treatment
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* Drug: MTC 01
* Drug: Fecal Microbiota Transplantation (FMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages eligible for study: 18 years and older Able and willing to provide written informed consent History of recurrent CDI defined as 2 episodes of CDI occurring within the previous 6 months (inclusive of the current episode) Subjects with a qualifying recurrent CDI episode, defined as: History of diarrhea (>=3 unformed stools per day for 2 or more consecutive days that is clinically consistent with CDI Documented positive stool test by local laboratory for toxigenic C. difficile (toxin EIA or PCR-based testing) for the current CDI episode within 60 days prior to randomization. Received a course of standard-of-care (SOC) CDI antibiotics for the most recent CDI episode (for 10 to 42 days, with exact duration, antibiotic type and dose at the discretion of the Investigator) Demonstrated adequate clinical response, defined as <= 3 unformed stools per day for 2 or more consecutive days during SOC CDI antibiotics prior to randomization. CDI symptoms started within 60 days prior to randomization. Exclusion Criteria: Female subjects who are pregnant or breastfeeding or are planning to become pregnant during the study. Women with reproductive potential should use a reliable method of birth control: Consistent use of an approved hormonal contraception (birth control pill/patches, rings); An intrauterine device (IUD); Contraceptive injection (Depo-Provera); Double barrier methods (Diaphragm with spermicidal gel or condoms with contraceptive foam); Sexual abstinence (no sexual intercourse) or Sterilization Known or suspected toxic megacolon, ileus or bowel obstruction at the time of enrollment. Subjects with active gastroenteritis due to infectious causes other than CDI Subjects with allergies to ingredients present in the investigational product Prior participation in studies of investigational live biotherapeutic products or FMT within the last 6 months. History of active diarrhea associated with inflammatory bowel disease (IBD). Major gastrointestinal surgery within the last 3 months before enrollment. Use of drugs that alter gut motility. History of acute leukemia or hematopoietic stem cell transplantation or myelosuppressive chemotherapy within 2 months prior to enrollment. Unable or unwilling to undergo a colonoscopy Inpatient status, though patients can be screened while inpatients, the must be outpatient for the planned colonoscopy. Anticipated immediate or upcoming surgery within 30 days Need for continued non-anti-CDI antibiotic therapy History of total proctocolectomy Patients who are unable to give informed consent Participation in a clinical trial in the preceding 30 days or simultaneously during this trial Severe food allergy (anaphylaxis or anaphylactoid-like reaction) Life expectancy < 6 months Unable to adhere to protocol requirements Patient who have received an FMT in the past year Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines that it will put the subject at greater risk from FMT Clinically significant abnormal lab values including but not limited to WBC >15 x 103/mm3, ANC <0.5 x 103/mm3, or laboratory evidence of acute kidney injury at Investigator's discretion, at screening If a patient is heavily immunosuppressed and is negative for CMV or EBV

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Four different interventions
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose MTC 01<br>High dose MTC 01 is 10 x 11 CFU slurry to be administered via colonoscopy | Drug: MTC 01<br>* Slurry to be administered via colonoscopy<br>|
| Experimental: Low Dose MTC 01<br>Low Dose MTC 01 is 10 x 10 CFU slurry to be administered via colonoscopy | Drug: MTC 01<br>* Slurry to be administered via colonoscopy<br>|
| Active Comparator: Low dose Fecal Microbiota Transplantation (FMT)<br>High dose FMT is 10 x 11 CFU slurry to be administered via colonoscopy | Drug: Fecal Microbiota Transplantation (FMT)<br>* Stool from a healthy donor is blended with salt water and made into a liquid solution rich in bacteria. This solution is sprayed into the recipient's colon during a colonoscopy<br>* Other names: Full spectrum FMT from a single donor;|
| Experimental: High Dose Fecal Microbiota Transplantation (FMT)<br>Low dose FMT is 10 x 10 CFU slurry to be administered via colonoscopy | Drug: Fecal Microbiota Transplantation (FMT)<br>* Stool from a healthy donor is blended with salt water and made into a liquid solution rich in bacteria. This solution is sprayed into the recipient's colon during a colonoscopy<br>* Other names: Full spectrum FMT from a single donor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-related serious adverse events (SAE) as assessed by NIH grading | Number of serious adverse events per NIH grading indications. Grade 1-5, where grade 3-5 are considered severe. Mild Moderate Severe Life threatening Death Serious Adverse Event (SAE): Any adverse event that: Results in death Is life threatening, or places the participant at immediate risk of death from the event as it occurred Requires or prolongs hospitalization Causes persistent or significant disability or incapacity Results in congenital anomalies or birth defects Is another condition which investigators judge to represent significant hazards | up to 24 weeks | 
| Number of participants with treatment-related adverse events as assessed by CTCAE 5.0 | Number of participants with treatment-related adverse events as assessed by CTCAE 5.0, grade 1-2, where higher grades indicate higher levels of impairment. Mild Moderate Severe Life threatening Death | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients who develop Clostridioides difficile (C difficile) | Recurrence of Clostridioides difficile (C difficile) within 8 weeks of receiving treatment. The stool C difficile toxin test detects harmful substances produced by the C difficile bacterium . This infection is a common cause of diarrhea after antibiotic use. Abnormal results mean that toxins produced by C difficile are seen in the stool and are causing diarrhea. | within 8 weeks |