Efficacy and Safety of FMT Capsule Treating Steroid-refractory GI-aGvHD

Investigator-initiated Trial to Explore the Efficacy and Safety of Fecal Microbiota Transplant (FMT) Capsule in the Treatment of Steroid-refractory Gastrointestinal Acute Graft Versus Host Disease Patients

Gastro-Intestinal Acute Graft Versus Host Disease (GI-aGVHD) is a complication of allogeneic stem cell transplant which is usually treated with steroids. When aGVHD does not respond to steroids it is described as steroid-refractory aGVHD. There is no standard therapy for steroid-refractory GI-aGVHD.

Fecal Microbiota Transplantation (FMT) is the transfer of fecal material from a healthy donor to a patient in order to restore the diversity of the intestinal microbiota. FMT is currently indicated for the treatment of recurrent Clostridium Difficile infection.

The investigators hypothesize that perturbations in the intestinal microbiota following allogeneic hematopoietic stem cell transplantation (HSCT) are essential for the development and propagation of acute graft-versus-host disease. Therefore, modification of HSCT recipients' gut microbiota using fecal transplantation from a healthy donor could be used to treat gut acute GVHD.

This study evaluates safety and feasibility of fecal microbiota transplantation with frozen capsules from healthy donors for the treatment of steroid resistant or steroid dependent acute graft-versus-host disease of the gut.

Study Overview

• Status: Unknown
• Conditions: Steroid-refractory Gastrointestinal Acute Graft Versus Host Disease
• Intervention / Treatment: Biological: Fecal Microbiota Transplant (FMT) Capsule

Detailed Description

This trial is designed to reconstruct the intestinal micro-ecology of patients with steroid-refractory gastrointestinal acute graft versus host disease (GI-aGvHD) by FMT. The primary objective is to evaluate the safety of FMT capsule in the treatment of steroid-refractory GI-aGvHD patients. The secondary objectives are as follows.

To observe the efficacy of FMT capsule in the treatment of steroid-refractory GI-aGvHD 28 days after the first administration.

To explore the characteristics of gut microbiota changes after FMT capsule treating steroid-refractory GI-aGvHD.

To evaluate the safety of FMT capsule treating steroid-refractory GI-aGvHD 12 weeks and 24 weeks after the first administration.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fen Huang; Phone Number: 13826204917; Email: 13826204917@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital, Southern Medical University
      • Contact: Fen Huang; Phone Number: +86-020-62787883; Email: 13826204917@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must be willing and able to sign the informed consent form and complete the follow-up visits.
2. 18-75 years old. No gender limitation.
3. Patients who can swallow the capsules without chewing.
4. Patients who were clinically diagnosed as steroid refractory GI-aGvHD. The diagnosis criteria are: experiencing GI-aGvHD clinical manifestations (e.g., abdominal cramps, diarrhea, stool blood) within 100 days after receiving hematopoietic stem cell transplant (HSCT); having Grade 2-4 gastrointestinal clinical symptoms; excluding diarrhea caused solely by pathogen infection; after adequate steroid treatment, disease progression on day 3, or with no change on day 7, or without complete response on day 14.
5. Patients who had complicated infection after the diagnosis of aGvHD, but are able to discontinue all the antibiotic therapy 12 hours before receiving FMT treatment.
6. ECOG scale ≤3
7. Basic body function indexes reach the following criteria: total neutrophil≥0.5*10^9/L, platelet count≥100*10^9/L, serum creatinine ≤1.5×upper limit of normal (ULN) or creatinine clearance≥40 mL/min, albumin≥25g/L.

Exclusion Criteria:

1. Patients with extremely serious grade IV aGvHD (life-threatening or with serious non-GvHD complication).
2. Refractory malignant condition.
3. Patients who have received two or more HSCT.
4. Patients who have active infection that has not been controlled and must receive antibiotic therapy, including diarrhea (non-GvHD diarrhea) caused by infection or antibiotics, excluding GvHD complicated infective diarrhea.
5. Patients who have gastrointestinal perforation or toxic intestinal.
6. Patients who have a history of severe allergic reactions.
7. Any condition in which PI do not consider it appropriate to participate (e.g., any medical history, treatment history, or abnormal history of testing data that may confuse the study results, or interfere with the patient's full participation in the study, or hurt the patient's benefit)
8. Female patients who have positive pregnancy test results or are breastfeeding. Women of childbearing age who refuse to use contraception one month after FMT treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Fecal Microbiota Transplant (FMT) Capsule	Biological: Fecal Microbiota Transplant (FMT) Capsule; When enrolled in the study, subjects will ingest 20 FMT capsules/day orally for 3 consecutive days. If the syndrome is not completely recovered or relapse 14 days after the first administration, the subject will receive a booster dose (20 capsules/day for 3 consecutive days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of adverse events (AEs)/serious adverse events (SAEs)	The number of FMT capsule associated AEs/SAEs occurring from the first administration of FMT to Day 28 (Day 1 is the last day of the first dose of FMT).	28 days
The severity of AEs/SAEs	The severity of FMT capsule associated AEs/SAEs occurring from the first administration of FMT to Day 28 (Day 1 is the last day of the first dose of FMT).	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	GI-aGvHD response rate (Complete response+Partial response) on Day 28 after the first dose of FMT (Day 1 is the last day of the first dose of FMT).	28 days
Changes in gut microbiota	Compare the gut microbiota diversity and major bacterial genus before and 28, 43(for subjects recieved 2 dose of FMT), 84 and 168 days after FMT treatment.	Days 28, 43, 84, and 168
The number of AEs/SAEs	The number of FMT capsule associated AEs/SAEs occurring from the first FMT treatment to Weeks 12 and 24 after the first FMT treatment.	Weeks 12 and 24
The severity of AEs/SAEs	The severity of FMT capsule associated AEs/SAEs occurring from the first FMT treatment to Weeks 12 and 24 after the first FMT treatment.	Weeks 12 and 24

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2020
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: October 28, 2020
• First Submitted That Met QC Criteria: November 9, 2020
• First Posted (Actual): November 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: XBI-302CT1004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No