Oral Aeromonas sp. MTB Phage Therapy for Pouchitis in Patients With Ulcerative Colitis (UC)

• MTB-targeted phage therapy (Biological): Aeromonas nov. subsp. macrophage-toxic bacteria (MTB) is a newly-identified enteropathogen associated with ulcerative colitis (UC). It secretes aerolysin to specifically damage colonic macrophages. MTB phage is a bacteriophage targeting this pathogen, which can safely and efficiently eliminate MTB in animal models. Treatment regimen: One bottle per dose, once daily, taken half an hour after meals for two weeks. Patient symptoms shall be assessed after each treatment session.

Primary outcomes

• Percentage of participants with a decrease in Modified Pouchitis Disease Activity Index (mPDAI) total score from baseline to week 14 [Baseline to Week 14]: The severity of pouchitis will be assessed using the modified Pouchitis Disease Activity Index (mPDAI). The mPDAI was used to evaluate patients' clinical symptoms (including stool frequency, rectal bleeding, fecal urgency, abdominal cramps, and presence of fever) and endoscopic inflammation (edema, granularity, fragility, loss of the vascular pattern, mucous exudates, and ulceration) . The percentage of participants with a decrease in mPDAI total score from baseline to Week 14 will be evaluated. A decrease in mPDAI total score is defined as a Week 14 mPDAI total score lower than the baseline mPDAI total score.

Secondary outcomes

• Percentage of Participants in Clinical Remission at Week 14 Based on the Modified Pouchitis Disease Activity Index (mPDAI) [Week 14]: Clinical remission of pouchitis will be assessed using the modified Pouchitis Disease Activity Index (mPDAI). Clinical remission is defined as an mPDAI score ≤4 points and a decrease of ≥2 points from baseline. The percentage of participants who meet the criteria for clinical remission at Week 14 will be evaluated.
• Percentage of Participants in Clinical Remission at Week 34 Based on the Modified Pouchitis Disease Activity Index (mPDAI) [Week 34]: Clinical remission of pouchitis will be assessed using the modified Pouchitis Disease Activity Index (mPDAI). Clinical remission is defined as an mPDAI score ≤4 points and a decrease of ≥2 points from baseline. The outcome will be reported as the percentage (%) of participants who meet both criteria for clinical remission at Week 34.
• Percentage of Participants With Sustained Clinical Remission at Week 34 Based on the Modified Pouchitis Disease Activity Index (mPDAI) [Week 14 through Week 34]: Sustained clinical remission will be assessed using the modified Pouchitis Disease Activity Index (mPDAI). Sustained clinical remission is defined as clinical remission at both Week 14 and Week 34. Clinical remission is defined as an mPDAI score ≤4 points and a decrease of ≥2 points from baseline. The percentage of participants who meet the criteria for sustained clinical remission at Week 34 will be evaluated.
• Percentage of Participants in Endoscopic Remission at Week 14 Based on the Modified Pouchitis Disease Activity Index Endoscopic Subscore (mPDAI-E) [Week 14]: Endoscopic remission will be assessed by endoscopic evaluation of the pouch. Endoscopic remission is defined as normalization of the mucosal appearance, clear vascular pattern, and absence of exudate or secretions.mPDAI-E≤1. The outcome will be reported as the percentage (%) of participants who meet the criteria for endoscopic remission at Week 14.
• Percentage of Participants in Endoscopic Remission at Week 34 Based on the Modified Pouchitis Disease Activity Index Endoscopic Subscore (mPDAI-E) [Week 34]: Endoscopic remission will be assessed by endoscopic evaluation of the pouch. Endoscopic remission is defined as normalization of the mucosal appearance, clear vascular pattern, and absence of exudate or secretions.mPDAI-E≤1. The outcome will be reported as the percentage (%) of participants who meet the criteria for endoscopic remission at Week 34.
• Active MTB Phage Concentration in Fresh Stool Samples (PFU/g) [24-48 hours after the first dose and Weeks 2, 8, 14, 24, and 34]: Active MTB phage concentration will be measured in fresh stool samples using a plaque assay. Approximately 1-2 g of fresh stool will be collected at each assessment. Active MTB phage concentration will be reported as plaque-forming units per gram of stool (PFU/g). Samples will be collected 24-48 hours after the first oral administration of MTB phage and at Weeks 2, 8, 14, 24, and 34.
• Fecal MTB Bacterial Abundance Measured by Culture (CFU/g) [Weeks 2, 8, 14, 24, and 34]: Fecal MTB bacterial abundance will be assessed by culture using an Aeromonas-selective culture medium. Fresh stool samples of approximately 1-2 g will be collected at Weeks 2, 8, 14, 24, and 34. MTB bacterial abundance will be reported as colony-forming units per gram of stool (CFU/g).
• Fecal MTB Bacterial Load Measured by Quantitative Polymerase Chain Reaction (qPCR) (CFU/mg) [Weeks 2, 8, 14, 24, and 34]: Fecal MTB bacterial load will be quantified using quantitative polymerase chain reaction (qPCR). Fresh stool samples of approximately 1-2 g will be collected at Weeks 2, 8, 14, 24, and 34. The qPCR cycle threshold (Ct) values will be converted to MTB bacterial load and reported as colony-forming units per milligram of stool (CFU/mg).
• Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score From Baseline to Week 34 (Points) [Baseline to Week 34]: Patient-reported quality of life will be assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). The change in IBDQ total score from baseline to Week 34 will be calculated by subtracting the baseline total score from the Week 34 total score. Scores will be reported in points.
• Incidence of Adverse Events Through Week 14 (%) [Week 14]: Adverse events will be coded using the Chinese version of the Medical Dictionary for Regulatory Activities (MedDRA). Adverse events will be summarized by study period (screening period and treatment period), System Organ Class (SOC), and Preferred Term (PT). The numbers of participants and events and the incidence of adverse events will be summarized. Treatment-related adverse events, serious adverse events, adverse events leading to study discontinuation, and important adverse events will also be summarized. Adverse events will be summarized by severity (mild, moderate, or severe).

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

1. Male and female subjects aged 18-70 years;
2. Confirmed diagnosis of ulcerative colitis (UC) prior to IPAA, with pouch takedown completed for at least 3 months;
3. Patients with pouchitis and an mPDAI score ≥ 5 points;
4. Positive stool test for MTB bacteria or Aeromonas aerolysin;
5. Subjects who agree to participate in this clinical study and have provided written informed consent.

Exclusion Criteria:

1. Patients with pre-operative diagnosis of familial polyposis, Crohn's disease, or indeterminate colitis;
2. Subjects who underwent temporary or permanent ileostomy without pouch construction;
3. Active cardiovascular and cerebrovascular diseases including coronary heart disease, hypertension, cerebral infarction;
4. Patients suffering from other systemic diseases, autoimmune diseases, malignant tumors, or other severe chronic illnesses;
5. History of psychotropic substance abuse;
6. Pregnant or lactating women;
7. Recent use of probiotic therapy;
8. Patients who have received antibiotics within the past three months;
9. Subjects deemed unsuitable for participation in this study at the investigator's discretion.

• Fangyu Wang, Principal investigator, Jinling Hospital, China