Study to Evaluate the Fecal Microbiota Transplantation (FMT) in the Treatment of Ulcerative Colitis

A Randomized, Open-label, Pilot Study to Evaluate the Fecal Microbiota Transplantation (FMT) in the Treatment of Ulcerative Colitis

The study is to evaluate the safety, feasibility, and preliminary efficacy of frozen FMT delivery via retention enema compared to lyophilized powder given in oral capsules as induction FMT in subjects with active UC. This study will also determine changes in microbiome (diversity and genera) and proportion of antibody-coated microbiota from baseline to after completion of FMT.

Study Overview

• Status: Recruiting
• Conditions: Active Ulcerative Colitis (UC)
• Intervention / Treatment: Drug: PRIM-DJ2727 - FROZEN; Drug: PRIM-DJ2727 - CAPSULES

Detailed Description

Studies have shown that microbiota disturbances occur in patients with ulcerative colitis (UC). This study will evaluate safety and preliminary efficacy of microbiota replacement treatment in active UC, and changes in microbiome (diversity and genera) and proportion of antibody-coated microbiota from baseline to after completion of FMT. Studies have shown that microbiota disturbances occur in patients with ulcerative colitis (UC). This study will evaluate safety and preliminary efficacy of microbiota replacement treatment in active UC, and changes in microbiome (diversity and genera) and proportion of antibody-coated microbiota from baseline to after completion of FMT.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Herbert L DuPont, MD; Phone Number: 713 500 6687; Email: herbert.l.dupont@uth.tmc.edu
• Study Contact Backup: Name: Zhi-Dong Jiang, Dr.PH; Phone Number: 713 500 9371

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston
      • Contact: Herbert L DuPont, MD; Phone Number: 713-500-9366; Email: herbert.l.dupont@uth.tmc.edu
      • Contact: Zhi-Dong Jiang, Dr.PH; Phone Number: 713 500 9371; Email: zhi-dong.jiang@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of active UC defined on clinical grounds (Partial Mayo score ≥ 3 with each subscore >1)
• Sexually active male and female subjects of childbearing potential must agree to use an effective method of birth control during the study.
• Female subjects of childbearing potential must have a negative urine Qualitative Human Chorionic Gonadotropin(HCG)pregnancy test at enrolment and on the Week 1, Day 1 of the Treatment prior to administration of study drug.
• Willing and able to sign an informed consent form and attend all study-related clinic visits, assessments, and follow-up phone calls.
• Subject has an attending physician who will provide the non-FMT care.

Exclusion Criteria:

• Subjects with sever UC (Mayo score of >7)
• Unable to take retention enema or multiple capsules orally.
• Females who are pregnant, breastfeeding, or planning to become pregnant during the study.
• Receipt of systemic non-topical antibiotics within 14 days of treatment day 1.
• Positive results for active HIV, Hepatitis B, or Hepatitis C infections.
• History of recurrent Clostridium difficile infection or FMT in the past 6-months.
• History of other active gastrointestinal conditions such as irritable bowel syndrome, microscopic colitis, celiac disease, short gut syndrome, colostomy, colectomy, gastrointestinal fistulae or strictures, chronic parasitic infections, diverticulitis etc.
• Known history of bile acid diarrhea
• Compromised immune system (e.g. primary immune disorders or clinical immunosuppression due to a medical condition or medication e.g. taking oral prednisone >20 mg a day or prednisone-equivalent)
• History of active cancer and/or ongoing chemotherapy (superficial non-metastatic cancers and maintenance chemotherapy are permitted).
• History of use of an investigational drug within 90 days prior to the screening visit.
• History of significant uncontrolled systemic disease that in the opinion of the study investigator could interfere with study participation and/or objectives.
• Life expectancy of < 1 year.
• In the opinion of investigator, subject for any reason, should be excluded from the study.
• Absolute neutrophil count (ANC) < 500IU/mL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: PRIM-DJ2727 - FROZEN	Drug: PRIM-DJ2727 - FROZEN; Patients with active UC will receive induction dose of 100 grams of stool via frozen retention enema, Fecal Microbiota Transplantation (FMT) product manufactured as PRIM-DJ2727-FROZEN administered in clinic. This consists of microbiota suspension from well-screened donors. Twice filtered fecal microbiota product diluted in saline to 500 mL containing 100g of study drug will be administered as frozen enema induction dose
Experimental: Experimental: PRIM-DJ2727 - CAPSULES	Drug: PRIM-DJ2727 - CAPSULES; Patients with active UC will receive induction dose of 100 grams of stool in orally administered enteric-coated capsules Fecal Microbiota Transplantation (FMT) product manufactured as PRIM-DJ2727-CAPSULES.These capsules consists of microbiota from well-screened donors. The induction dose of enteric-coated capsules will be derived from 100 grams stool.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease severity as assessed by the Partial Mayo Score (PMS) for Ulcerative Colitis (UC)	This is a 3 item questionnaire and each is measured from 0-3, for a maximum score of 9 a higher number indicating worse outcome	week 5
Change in fecal microbiota diversity and genera as assessed by sequencing		Baseline,end of treatment (4 weeks after baseline)
Change in proportion of antibody-coated microbiota as assessed by the antibiotic susceptibility test		Baseline,end of treatment (4 weeks after baseline)
Safety as assessed by the adverse events	Adverse events include death, life-threatening adverse event, hospitalization ≥ 24 hours, prolongation of existing hospitalization, substantial disruption of the ability to conduct normal life functions, congenital abnormally/birth defect, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or other important events that jeopardize the patient and may require medical or surgical intervention (e.g. allergic bronchospasm requiring intensive treatment)	3 months after last dose
Safety as assessed by the adverse events	Adverse events include death, life-threatening adverse event, hospitalization ≥ 24 hours, prolongation of existing hospitalization, substantial disruption of the ability to conduct normal life functions, congenital abnormally/birth defect, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or other important events that jeopardize the patient and may require medical or surgical intervention (e.g. allergic bronchospasm requiring intensive treatment)	6 months after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quality of life as assessed by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score	This is a 10 item questionnaire and each is scored from 1(all of the time) to 7 (none of the time) for a maximum score of 70 a higher number indicating better quality of life	baseline, week 5, early termination(if applicable)
Change in anxiety and depression as assessed by the Hospital Anxiety and Depression Scale (HADS)	This is a fourteen-item questionnaire to assess anxiety and depression. Seven items are related to anxiety symptoms and seven to depressive symptoms. Each item is coded from 0 to 3. The scores for anxiety and depression can therefore vary from 0 to 21, a higher number indicating worse outcome	baseline, week 5, early termination(if applicable)
Change in fecal microbiota diversity and genera as assessed by sequencing		Baseline,end of treatment (4 weeks after baseline), 6 months
Change in proportion of antibody-coated microbiota as assessed by the gut microbiota taxonomy by sequencing		Baseline,end of treatment (4 weeks after baseline), 6 months follow up

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Herbert L DuPont, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2027

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: March 23, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: HSC-MS-23-0016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No