Safety Evaluation of Fecal Microbiota Transplantation in Severe Alcoholic Hepatitis

NCT05006430 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-43752
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, randomized, parallel assignment, and double-blind placebo-controlled pilot study to characterize the intestinal microbiome in patients with severe Alcoholic Hepatitis (SAH) and evaluate the safety and the trends in improvement of diversity of intestinal microbiome following administration of lyophilized capsules containing microbiota suspension from well screened health donors. The study aims to enroll 50 patients with SAH who will be randomly assigned in 1:1 where 25 patients will be assigned to receive orally administered lyophilized PRIM-DJ2727 and Standard of Care (SOC) and the other 25 patients will be assigned to receive placebo and SOC for 4 weeks.

Conditions

Alcoholic Hepatitis

Keywords

Severe alcoholic hepatitis

Outcome Measures

Primary Outcomes (5)

• To Assess survival in patients with severe alcoholic hepatitis receiving PRIM-DJ2727 capsules in comparison to standard of care.

  PRIM-DJ2727 is given orally at dose of 30 gm once daily for a week then, once weekly for 3 weeks

  [Day1 to 12 month]

• To assess the change in gut microbiome population associated with severe alcoholic hepatitis patients from baseline in study population at 4 weeks.

  Microbiome will be characterized at baseline and at 4 weeks in terms of predominant genera and number of each genus population.

  At [Baseline] [4 weeks]

• To assess the change in gut microbiome population associated with severe alcoholic hepatitis patients from baseline in study population at 6 months.

  Microbiome will be characterized at baseline and at 6 months in terms of predominant genera and number of each genus population.

  At [Baseline] [6 months]

• To assess the change in gut microbiome population associated with severe alcoholic hepatitis patients from baseline in study population at 9 months.

  Microbiome will be characterized at baseline and at 9 months in terms of predominant genera and number of each genus population.

  At [Baseline] [9 months]

• To assess the change in gut microbiome population associated with severe alcoholic hepatitis patients from baseline in study population at 12 months.

  Microbiome will be characterized at baseline and at 12 months in terms of predominant genera and number of each genus population.

  At [Baseline] [12months]

Secondary Outcomes (20)

• To assess change in the prognostic scores of Model for End Stage Liver Disease (MELD) from baseline in the study population at 4 weeks.

  At [Baseline] [4 weeks]

• To assess change in the prognostic scores of Model for End Stage Liver Disease (MELD) from baseline in the study population at 12 weeks.

  At [Baseline] [12 weeks]

• To assess change in the prognostic scores of Model for End Stage Liver Disease (MELD) from baseline in the study population at 6 months.

  At [Baseline] [6 months]

• To assess change in the prognostic scores of Model for End Stage Liver Disease (MELD) from baseline in the study population at 9 months.

  At [Baseline] [9 months]

• To assess change in the prognostic scores of Model for End Stage Liver Disease (MELD) from baseline in the study population at 12 months.

  At [Baseline] [12 months]

Study Arms (2)

Intervention Arm

ACTIVE COMPARATOR

Subjects will receive Standard of Care (SOC), based on AASLD/EASL guidelines and one dose of PRIM-DJ2727 (30 grams of stool/dose \~ 3 capsules) every day for a week followed by once weekly for 3 weeks, amounting to total 10 doses. PRIM-DJ2727 (microbiota suspension) is an intestinal microbial suspension prepared form stool obtained from carefully and thoroughly screened healthy human donors. It will be provided by University of Texas School of Public Health.

Biological: Fecal Microbiota Transplantation

Placebo Arm

PLACEBO COMPARATOR

Subjects will receive Standard of Care (SOC), based on AASLD/EASL guidelines and one dose of Placebo every day for a week followed by once weekly for 3 weeks, amounting to total 10 doses. Placebo will be identical to the investigational product but will not contain active PRIM-DJ2727.

Other: Placebo

Interventions

Fecal Microbiota Transplantation BIOLOGICAL

It's an intestinal microbial suspension prepared form stool obtained from carefully and thoroughly screened healthy human donors.

Also known as: (PRIM-DJ2727), FMT

Intervention Arm

Placebo OTHER

Placebo will be identical to the investigational product but will not contain fecal material.

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any gender; male or female; aged 18- 75 years old.
• Severe alcoholic hepatitis defined as 2.1 Onset of jaundice within prior 8 weeks. 2.2 Ongoing alcohol consumption of \>40 g/day (3 drinks) in females or \>60 g/day (4 drinks) in males for 6 months or more, with less than 60 days of abstinence before the onset of jaundice. 2.3 Aspartate aminotransferase \>50, Aspartate aminotransferase/Alanine aminotransferase ratio \> 1.5, BUT both values \<400 IU/L.
• Serum total bilirubin \>3.0 mg/dl. 2.5 MELD score \>15 and/or Maddrey DF score of ≥32.

You may not qualify if:

• Non-alcoholic related liver diseases.
• Patients with swallowing dysfunction at risk of aspiration.
• Patients at risk for or with known anatomic or functional gastrointestinal (GI) obstruction or who have undergone major intra-abdominal surgery in the last year.
• Patients who have undergone placement of a portosystemic shunt, infection of which may require prolonged antibiotics.
• Patients with any congenital or acquired immunodeficiency (Other than liver disease)
• Uncontrolled infections, sepsis, or GI bleeding.
• Presence of cancer especially patients with skin cancer who is receiving or may receive systemic chemotherapy or immunotherapy during the study period.
• Underlying disease that might be exacerbated by proposed treatments (e.g. HCV, HBV, HIV, TB).
• Serum creatinine \>2.5 mg/dl at presentation.
• Pregnant and breastfeeding patients.
• Active use drug addiction.
• PI thinks their participation would pose a health risk e.g. patients with very severe AH with MELD score \>30 or Maddrey DF \> 60 or patient will be getting liver transplantation imminently.
• Any other major illness/ condition that in the investigators judgment, will substantially increase the risk to the participant.

Sponsors & Collaborators

• Prasun Kumar Jalal: lead

Study Sites (1)

Baylor St. Luke Medical Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Hepatitis, Alcoholic

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine-Hepatology

Study Record Dates

• First Submitted: June 4, 2021
• First Posted: August 16, 2021
• Study Start: January 21, 2023
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: January 23, 2025

Record last verified: 2024-08

Locations

US (1)