Fecal Microbiota Transplant (FMT) Capsule for Improving the Efficacy of GI-aGVHD

Evaluating Safety and Efficacy of GI-XBI-302 in Patients With Glucocorticoid-refractory Acute Graft vs. Host Disease After Allogeneic Stem Cell Transplantation

This study aims to determine whether the fecal microbiota transplant (FMT) capsule improves the response rate of GI-aGVHD in patients with glucocorticoid-refractory acute graft vs. host disease after allogeneic stem cell transplantation

Study Overview

• Status: Not yet recruiting
• Conditions: GVHD
• Intervention / Treatment: Biological: FMT

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: yanli zhao; Phone Number: 0316-3306412; Email: 13121053519@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. GVHD within 100 days after allogeneic hematopoietic stem cell transplantation (allo HSCT);

  2. Age 18 - 65 years old, regardless of gender;

  3. Patients with grade 3 or 4 gastrointestinal involvement (aGVHD) according to the International Alliance (Magic) classification standard;

  4. Patients with glucocorticoid resistant GI aGVHD are diagnosed. According to the expert consensus of Chinese allogeneic hematopoietic stem cell transplantation for the treatment of hematological diseases (III) - acute graft-versus-host disease (2020 Edition), the definition of glucocorticoid resistant acute GVHD is Thomas' hematopoietic cell transplantation: stem cell transplantation (5th Edition) Glucocorticoid resistance was defined as PD at 3 days, NR at 7 days or Cr not reached at 14 days after first-line treatment.

  5. ECoG 3 points or less;

  6. Stop prophylactic antibiotics at least 12 hours before FMT treatment;

  7. Be able and willing to sign informed consent;

  8. Patients who are capable of swallowing capsules and can complete the study;

Exclusion Criteria:

• 1. There are active but uncontrolled infections, except GVHD complicated with infectious diarrhea;

  2. Gastrointestinal perforation, active gastrointestinal bleeding, small intestinal obstruction, toxic megacolon or other serious gastrointestinal diseases not caused by GVHD;

  3. Have a history of severe allergic reaction; Or known to be allergic to any ingredient of intestinal bacteria capsule xbi-302;

  4. Any serious disease that can increase the risk of patients participating in the study;

  5. Female subjects with positive pregnancy test and lactation, or female subjects of childbearing age who refuse to take contraceptive measures during the study;

  6. According to the judgment of the researcher, the patients with high dynamic diarrhea can not stay in the intestine for enough time to dissolve the capsule.

  7. HIV, HBV, HCV and syphilis are positive;

  8. After colectomy;

  9. Participate in other intervention clinical studies within 4 weeks before the screening period;

  10. The expected survival time is less than 12 weeks;

  11. The basic body function test is inferior to the following standards: total neutrophils (neu) < 0.5 (x109 / L), platelet count (PLT) < 30 (x109 / L), serum creatinine (CR) > 1.5 times the maximum normal value (ULN), albumin (ALB) < 25g / L;

  12. There is any situation that the researcher thinks is not suitable for inclusion (any history of medical history, treatment history or abnormal test data that may confuse the results of this study, interfere with the subject's whole participation in the study, or harm the interests of the subject).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FMT; 60 capsules per day for 2 day	Biological: FMT; Fecal Microbiota Transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	assessed by Overall Response Rate (ORR) at Day 28	Day 28
AE	assessed all related a grade 3 or above adverse event (AE) at Day 28	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE	assessed all related adverse event (AE)	up to 25 weeks
Shannon index	changes of Shannon index	up to 25 weeks
colonization bacteria analysis	the number and relative abundance of bacteria that originally existed only in the capsule but could still be detected in the stool samples of subjects	up to 25 weeks
PFS	Kaplan-Meier Curve	up to 25 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabonomics	The changes of calprotectin, Is, SCFA and bile acid were compared	up to 25 weeks
biomarkers	The changes of IL-6、IL-8、sTNFR1、sST2、Reg3a、Elafin were compared	up to 25 weeks
Immunohistochemistry	The phenotypes and subsets of CD4 and CD8 positive T cells, B cells, NK cells and monocytes were compared	up to 25 weeks
Proportion of patients	Proportion of patients with hormone dosage ≤ 20mg / day equivalent to equivalent converted dose of prednisolone	up to 25 weeks
The proportion of patients	who stopped antibiotics was compared.	up to 25 weeks
Percentage of patients	Percentage of patients who died due to GVHD	up to 25 weeks

Collaborators and Investigators

• Sponsor: Shenzhen Xbiome Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2021
• Primary Completion (ANTICIPATED): March 2, 2023
• Study Completion (ANTICIPATED): March 2, 2023

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: October 15, 2021
• First Posted (ACTUAL): October 26, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 26, 2021
• Last Update Submitted That Met QC Criteria: October 15, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: XCT4843002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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