Investigational Microbiota Restoration Therapeutic for Hepatic Encephalopathy

NCT04155099 | Terminated Phase 2 FDA Drug

• 1 other identifier: 2019.193
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Individuals with cirrhosis are likely to develop overt hepatic encephalopathy for which diagnostic modalities and treatment options are limited. The purpose of this study is to determine if individuals with cirrhosis who experience hepatic encephalopathy would benefit from investigational microbiota restoration therapy due to their inherent cognitive alterations. Analysis for a correlation between changes in microbiome composition and specific blood biomarkers could allow for earlier diagnosis of HE which could then be treated earlier and with novel treatments.

Conditions

Hepatic Encephalopathy; Cirrhosis, Liver

Keywords

encephalopathy

Outcome Measures

Primary Outcomes (1)

• Change in cognitive function at 1 month post-FMT as measured by change in response times on EncephalApp (Stroop test)

  Determine whether microbiota restoration therapy improves cognition 1 month after treatment by measuring differences in time scores from EncephalApp. The app times participants in seconds (s) in variations of the Stroop Test. The average (s) across all trials will be reported as well as the difference in (s) between (trial 1)-(trial 5). Longer completion times indicate greater cognitive impairment, while a decrease in completion time from trial 1 to trial 5 indicates learning (cognitive improvement). The scale for this measure is theoretically 0s-500s.

  1 month

Secondary Outcomes (3)

• Number of HE episodes

  1 month to 12 months

• Engraftment of FMT as assessed by change in type and abundance of gut microbiota following shotgun sequencing

  1 month to 12 months

• Change in cognitive function at 3, 6 and 12 months post-FMT as measured by change in response times on EncephalApp (Stroop test)

  3 to 12 months

Other Outcomes (1)

• Correlations of clinical variables with primary and secondary outcomes

  Duration of the study (0 days to 12 months)

Study Arms (3)

High dose

EXPERIMENTAL

Capsules of active drug will be supplied in 8-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment.

Biological: RBX7455

Low dose

EXPERIMENTAL

Capsules of active drug will be supplied in 4-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment.

Biological: RBX7455

pill quantity-matched Placebo

PLACEBO COMPARATOR

Capsules of inactive compound will be supplied in 8- or 4-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment.

Biological: Placebo

Interventions

RBX7455 BIOLOGICAL

RBX7455 is a preparation of live intestinal microorganisms (active drug) purified from stool donations obtained from healthy, screened donors, mixed with preservative, lyophilized, and put into capsules. The capsules are taken orally (i.e., by mouth). After ingestion, these freeze-dried microorganisms can reconstitute and proliferate in the gut.

Also known as: Microbiota Restoration Therapy

High dose; Low dose

Placebo BIOLOGICAL

Capsule with cellulose filler

pill quantity-matched Placebo

Eligibility Criteria

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

You may qualify if:

• Individuals who are male or female and are between the ages of 18 and 70 years.
• Individuals with a current diagnosis of liver cirrhosis as evidenced by one or more of the following:
• a. Liver Biopsy
• OR a clinical suspicion of cirrhosis based on the presence of one or more of the following criteria:
• Radiologic evidence of varices, cirrhosis or portal hypertension
• Laboratory evidence of platelet count \<100,000 or AST/ALT ratio \>1
• Endoscopic evidence of varices or portal gastropathy
• Elastography (i.e. Fibroscan)
• Individuals must have at least one previously documented episode of HE.
• Individuals must be able to read and write in the English language.
• Individuals must be able and willing to utilize the electronic device necessary to measure cognitive function without assistance from outside individuals once the training phase has been completed.
• Individuals must be able to provide valid informed consent prior to any study related procedures.

You may not qualify if:

• Individuals who are color-blind.
• Individuals actively using psychotropic substances including alcohol.
• Individuals who are pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Study individuals are expected to attest to this fact during their participation time. Females who are not surgically sterile or having undergone greater than one year of menopause will receive urine pregnancy tests at screening and initial drug dosing.
• Presence of TIPS (transjugular intrahepatic portosystemic shunt).
• Individuals with an active bacterial infection and are taking antibiotics for those infections at time of consent.
• Individuals with ANC \<800 (neutropenia).
• Individuals with MELD \>17.
• Individuals with platelet count \<35,000/mm3.
• Individuals who are immunocompromised due any of the following reasons:
• HIV infection (CD4 count \<200/mm3) or AIDS diagnosis
• Inherited/primary immunodeficiency disorders
• Treatment with any anti-neoplastic agent within the last 3 months (excluding locoregional therapy for hepatocellular carcinoma)
• Treatment with any immunosuppressant medications \[including but not limited to monoclonal antibodies to B cells or T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil\] within the last 3 months
• Individuals who have previously undergone FMT.
• Individuals with a history of colorectal cancer (all stages).

Sponsors & Collaborators

• Ochsner Health System: lead
• Rebiotix Inc.: collaborator

Study Sites (1)

Ochsner Medical Center

Jefferson, Louisiana, 70121, United States

Location

MeSH Terms

Conditions

Hepatic Encephalopathy; Liver Cirrhosis; Brain Diseases

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Julia Garcia-Diaz, MD

  Ochsner Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a double-blinded study meaning both Ochsner study staff and participating individuals will not know to which group they are assigned/randomized. A third party will be responsible for providing study participant randomization and recording the exact treatment to which all study participants are assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Study individuals will be placed into one of four study treatment groups: High dose investigational microbiota restoration therapeutic RBX7455 group, Low dose investigational microbiota restoration therapeutic RBX7455 group, or a pill quantity-matched Placebo group. Individuals will be randomized in a 1:1:1/2:1/2 manner. It is anticipated of the 75 potentially enrolled individuals, 50 will receive active treatment (high or low dose investigational microbiota restoration therapeutic) and 25 will receive placebo.

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: November 7, 2019
• Study Start: March 1, 2021
• Primary Completion: July 30, 2023
• Study Completion: July 30, 2023
• Last Updated: October 3, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)