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

Browse trials for

• Pouchitis 50
• Colitis, Ulcerative 1,530

Pouchitis

50 studies on the registry are indexed under Pouchitis; 13 are open to participants now.

This study's planned enrollment of 12 is below the median of 20 across 42 interventional studies indexed under Pouchitis.

Lead sponsor

Jinling Hospital, China is the lead sponsor of 130 studies on the registry; 35 are open to participants now.

Study arms

• Experimental
  Pouchitis

  Adult patients aged 18-70 years with pouchitis after IPAA surgery for ulcerative colitis, who test positive for MTB bacteria or aerolysin\*\*.

  Biological: MTB-targeted phage therapy

Interventions

• BiologicalMTB-targeted phage therapy

  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

1. Percentage of participants with a decrease in Modified Pouchitis Disease Activity Index (mPDAI) total score from 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.

   Time frame: Baseline to Week 14

Secondary outcomes

1. Percentage of Participants in Clinical Remission at Week 14 Based on the Modified Pouchitis Disease Activity Index (mPDAI)

   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.

   Time frame: Week 14

2. Percentage of Participants in Clinical Remission at Week 34 Based on the Modified Pouchitis Disease Activity Index (mPDAI)

   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.

   Time frame: Week 34

3. Percentage of Participants With Sustained Clinical Remission at Week 34 Based on the Modified Pouchitis Disease Activity Index (mPDAI)

   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.

   Time frame: Week 14 through Week 34

4. Percentage of Participants in Endoscopic Remission at Week 14 Based on the Modified Pouchitis Disease Activity Index Endoscopic Subscore (mPDAI-E)

   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.

   Time frame: Week 14

5. Percentage of Participants in Endoscopic Remission at Week 34 Based on the Modified Pouchitis Disease Activity Index Endoscopic Subscore (mPDAI-E)

   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.

   Time frame: Week 34

6. Active MTB Phage Concentration in Fresh Stool Samples (PFU/g)

   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.

   Time frame: 24-48 hours after the first dose and Weeks 2, 8, 14, 24, and 34

7. Fecal MTB Bacterial Abundance Measured by Culture (CFU/g)

   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).

   Time frame: Weeks 2, 8, 14, 24, and 34

8. Fecal MTB Bacterial Load Measured by Quantitative Polymerase Chain Reaction (qPCR) (CFU/mg)

   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).

   Time frame: Weeks 2, 8, 14, 24, and 34

9. Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score From Baseline to Week 34 (Points)

   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.

   Time frame: Baseline to Week 34

10. Incidence of Adverse Events Through 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).

    Time frame: Week 14

Individual participant data

Plan to share: No