Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Vedanta Biosciences, Inc. | INDUSTRY |
| American College of Gastroenterology | OTHER |
| American Association for the Study of Liver Diseases | OTHER |
Not provided
Not provided
Not provided
Not provided
This research is studying the use of a new drug to learn about its safety and efficacy as a treatment for hepatic encephalopathy.
Eligible participants will be enrolled and given oral antibiotics followed by 14 days of the study drug (placebo vs.VE303). There will be visits as well as other procedures to collect blood and stool samples, and have tests of your cognition (thinking) for this research study.
The hypothesis is that VE303 will safely and effectively improve cognitive function in patients with a history of overt hepatic encephalopathy.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| VE303 | Experimental | VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Starting the last day of oral vancomycin (Day 1), subjects randomized to this arm will take 5 capsules of placebo for 14 days taken once daily. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced Serious Adverse Events up to Week 6 | An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of the investigator, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. | Week 6 |
| Change in Psychometric Hepatic Encephalopathy Score (PHES) as a Measure of Cognitive Function From Pre-vancomycin to Week 6 | This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (1+ for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18, where +6 is the best function and -18 is worst function. | baseline (pre-vancomycin), Week 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Hospitalizations for Overt Hepatic Encephalopathy (OHE) up to Week 26 | Shown as a rate (# of episodes/ number of patients) = # per patient. | 26 weeks |
| Adverse Events up to Week 26 | total number of AEs |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Serum and Stool Biomarkers From Pre-vancomycin to Week 26 | baseline (pre-vancomycin), week 26 |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Patricia Bloom, MD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
One patient was consented but then failed to meet eligibility criteria soon after enrollment. They did not initiate vancomycin and were not randomized.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo: Starting the last day of oral vancomycin (Day 1), participants randomized to this arm will take 5 capsules of placebo for 14 days taken once daily. Oral vancomycin: All enrolled participants will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d). |
| FG001 | VE303 | VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia. VE303: Starting the last day of oral vancomycin (Day 1), participants randomized to this arm will take 5 capsules of VE303 taken daily for 14 days. The quantity of each strain is proportioned to assure a specific per-strain per-capsule titer. The 8 strains are blended together with a micro-crystalline cellulose flow agent and placed in enteric capsules. Oral vancomycin: All enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo: Starting the last day of oral vancomycin (Day 1), participants randomized to this arm will take 5 capsules of placebo for 14 days taken once daily. Oral vancomycin: All enrolled participants will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d). |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Experienced Serious Adverse Events up to Week 6 | An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of the investigator, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. | Posted | Count of Participants | Participants | Week 6 |
|
6 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo: Starting the last day of oral vancomycin (Day 1), participants randomized to this arm will take 5 capsules of placebo for 14 days taken once daily. Oral vancomycin: All enrolled participants will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalized for Hepatic Encephalopathy | Hepatobiliary disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Distension | Gastrointestinal disorders | Systematic Assessment | This adverse event occurred in conjunction with others |
Note that for PHES and some other outcome measures, the drop out rate was high.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patricia Bloom, MD | University of Michigan | 734-647-5944 | ppbloom@med.umich.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 16, 2023 | Apr 10, 2024 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D005355 | Fibrosis |
| D006501 | Hepatic Encephalopathy |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017093 | Liver Failure |
| D048550 | Hepatic Insufficiency |
Not provided
Not provided
| ID | Term |
|---|---|
| D014640 | Vancomycin |
| ID | Term |
|---|---|
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D010455 | Peptides |
Not provided
Not provided
Subjects will be randomized 2:1 to VE303 vs placebo. There will be no stratification.
After the trial enrolls the first 9 patients, an interim analysis to evaluate safety of VE303 in this population will take place. If there is no concern for a higher rate of Serious adverse events (SAEs) in the VE303 group, enrollment will continue to reach a total of 18 patients.
Not provided
Not provided
Study staff will remain blinded to subject randomization until the study period is over.
| VE303 | Drug | Starting the last day of oral vancomycin (Day 1), subjects randomized to this arm will take 5 capsules of VE303 taken daily for 14 days. The quantity of each strain is proportioned to assure a specific per-strain per-capsule titer. The 8 strains are blended together with a micro-crystalline cellulose flow agent and placed in enteric capsules. |
|
| oral vancomycin | Drug | All enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d). |
|
| up to week 26 |
| Change in Patient Reported Outcome Measurement Information System (PROMIS) Global Health Reported From Pre-vancomycin to Week 26 | The PROMIS v 1.1 is a 10 question scale where participants select answers from (0) up to (10). Higher scores indicate better quality of life. Results are presented as change in scores pertaining to physical and mental health. | baseline (pre-vancomycin), week 26 |
| Time to Overt HE | This is the number of days from Day 1 of Vancomycin to the first OHE event or to the end of study, whichever came first. | up to 26 weeks |
| Change in Microbiome Composition From Pre-vancomycin to Week 26 | This will be calculated by alpha diversity between stool collection timepoints and will have metagenomic sequencing on stool to assess this. The Shannon index is a calculation used to measure the diversity of microbial species within a sample, taking into account both the number of different species present (richness) and how evenly distributed their abundances are (evenness). A higher Shannon index indicates a more diverse microbial community, meaning a wider variety of microbes present in roughly equal proportions. The Shannon index was calculated for each sample as part of metagenomic sequencing analysis performed with the tool MetaPhlAn (version 3.0). The minimum Shannon index value is 0 and it could theoretically go to infinity; however, typical values range more in the 1-4 range. Now, this outcome is measuring the CHANGE in Shannon index, therefore negative values are possible, if the diversity of specimens dropped from the pre-vancomycin to the week 26 samples. | baseline (pre-vancomycin), week 26 |
| PHES From Pre-vancomycin to Week 26 | This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (+1 for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18. | pre-vancomycin up to week 26 |
| VE303 |
VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia. VE303: Starting the last day of oral vancomycin (Day 1), participants randomized to this arm will take 5 capsules of VE303 taken daily for 14 days. The quantity of each strain is proportioned to assure a specific per-strain per-capsule titer. The 8 strains are blended together with a micro-crystalline cellulose flow agent and placed in enteric capsules. Oral vancomycin: All enrolled participants will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Baseline Psychometric HE Score (PHES) | This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (1+ for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18, where +6 is the best function and -18 is worst function | Mean | Standard Deviation | units on a scale |
|
| OG001 | Placebo | Placebo: Starting the last day of oral vancomycin (Day 1), participants randomized to this arm will take 5 capsules of placebo for 14 days taken once daily. Oral vancomycin: All enrolled participants will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d). |
|
|
| Primary | Change in Psychometric Hepatic Encephalopathy Score (PHES) as a Measure of Cognitive Function From Pre-vancomycin to Week 6 | This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (1+ for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18, where +6 is the best function and -18 is worst function. | Posted | Mean | Standard Deviation | units on a scale | baseline (pre-vancomycin), Week 6 |
|
|
|
| Secondary | Number of Hospitalizations for Overt Hepatic Encephalopathy (OHE) up to Week 26 | Shown as a rate (# of episodes/ number of patients) = # per patient. | Posted | Mean | Full Range | episodes/patient | 26 weeks |
|
|
|
| Secondary | Adverse Events up to Week 26 | total number of AEs | Posted | Number | adverse events | up to week 26 |
|
|
|
| Secondary | Change in Patient Reported Outcome Measurement Information System (PROMIS) Global Health Reported From Pre-vancomycin to Week 26 | The PROMIS v 1.1 is a 10 question scale where participants select answers from (0) up to (10). Higher scores indicate better quality of life. Results are presented as change in scores pertaining to physical and mental health. | Data is missing from two VE303 participants because they did not provide it. | Posted | Mean | Standard Deviation | score on a scale | baseline (pre-vancomycin), week 26 |
|
|
|
| Secondary | Time to Overt HE | This is the number of days from Day 1 of Vancomycin to the first OHE event or to the end of study, whichever came first. | Posted | Mean | Full Range | days | up to 26 weeks |
|
|
|
| Secondary | Change in Microbiome Composition From Pre-vancomycin to Week 26 | This will be calculated by alpha diversity between stool collection timepoints and will have metagenomic sequencing on stool to assess this. The Shannon index is a calculation used to measure the diversity of microbial species within a sample, taking into account both the number of different species present (richness) and how evenly distributed their abundances are (evenness). A higher Shannon index indicates a more diverse microbial community, meaning a wider variety of microbes present in roughly equal proportions. The Shannon index was calculated for each sample as part of metagenomic sequencing analysis performed with the tool MetaPhlAn (version 3.0). The minimum Shannon index value is 0 and it could theoretically go to infinity; however, typical values range more in the 1-4 range. Now, this outcome is measuring the CHANGE in Shannon index, therefore negative values are possible, if the diversity of specimens dropped from the pre-vancomycin to the week 26 samples. | Participants analyzed reflect participants from whom week 26 stool samples could be obtained. Not every participant was able to provide a stool sample at week 26, and therefore this outcome was missing for those patients. | Posted | Mean | Standard Deviation | Shannon index | baseline (pre-vancomycin), week 26 |
|
|
|
|
| Secondary | PHES From Pre-vancomycin to Week 26 | This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (+1 for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18. | Note: Significant data loss due to some participants not participating in this test at 26 weeks | Posted | Mean | Full Range | score on a scale | pre-vancomycin up to week 26 |
|
|
|
|
| Other Pre-specified | Change in Serum and Stool Biomarkers From Pre-vancomycin to Week 26 | Not Posted | baseline (pre-vancomycin), week 26 | Participants |
| 0 |
| 6 |
| 1 |
| 6 |
| 6 |
| 6 |
| EG001 | VE303 | VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia. VE303: Starting the last day of oral vancomycin (Day 1), participants randomized to this arm will take 5 capsules of VE303 taken daily for 14 days. The quantity of each strain is proportioned to assure a specific per-strain per-capsule titer. The 8 strains are blended together with a micro-crystalline cellulose flow agent and placed in enteric capsules. Oral vancomycin: All enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d). | 0 | 12 | 5 | 12 | 12 | 12 |
| Inpatient Catheter Service | Surgical and medical procedures | Systematic Assessment |
|
| Hyperglycemic Hyperosmolar Syndrome | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hospitalization due to Ascites Accumulation | Hepatobiliary disorders | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
|
| Hospitalization for Diabetic Ketoacidosis | Metabolism and nutrition disorders | Systematic Assessment | This adverse event occurred in conjunction with others |
|
| Pain and Bleeding from Surgical Site | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Wound Dehiscence | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Hospitalization due to Esophageal Bleed | Gastrointestinal disorders | Systematic Assessment |
|
| Elective Total Hip Replacement | Surgical and medical procedures | Systematic Assessment |
|
| Hospitalization due to Post-Surgical Complications | Injury, poisoning and procedural complications | Systematic Assessment |
|
|
| Increased Bowel Movements | Gastrointestinal disorders | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Systematic Assessment |
|
| Bruising | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment | This adverse event occurred in conjunction with others |
|
| Decreased Lymphocyte Count | Blood and lymphatic system disorders | Systematic Assessment |
|
| Decreased Platelet Count | Blood and lymphatic system disorders | Systematic Assessment |
|
| Alkaline Phosphatase Increase | Hepatobiliary disorders | Systematic Assessment |
|
| Worsening Gout Symptoms | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment | This adverse event occurred in conjunction with others |
|
| Alanine Transaminase Increase | Hepatobiliary disorders | Systematic Assessment |
|
| Increased Blood Bilirubin | Hepatobiliary disorders | Systematic Assessment |
|
| Increased Lipase | Gastrointestinal disorders | Systematic Assessment |
|
| Leukopenia/Decreased White Blood Cell Count | Blood and lymphatic system disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment | This adverse event occurred in conjunction with others |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment | This adverse event occurred in conjunction with others |
|
| Increased Amylase Levels | Gastrointestinal disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Skin Numbness | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Leg Pain and Swelling | General disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Skin Discoloration (foot) | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Easy Bleeding | Blood and lymphatic system disorders | Systematic Assessment |
|
| Long Sleeping Duration | General disorders | Systematic Assessment |
|
| Limb Weakness/Numbness | Nervous system disorders | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Decreased Neutrophil Count | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hypoalbuminemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Bilateral Hand Tremors | Nervous system disorders | Systematic Assessment | This adverse event occurred in conjunction with others |
|
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Lightheadedness | General disorders | Systematic Assessment | This adverse event occurred in conjunction with others |
|
| Weight Gain | General disorders | Systematic Assessment |
|
| Flu Symptoms | Infections and infestations | Systematic Assessment |
|
| Mild Edema | General disorders | Systematic Assessment |
|
| COVID | Infections and infestations | Systematic Assessment | This adverse event occurred in conjunction with others |
|
| Bleeding from preexisting ear condition | Ear and labyrinth disorders | Systematic Assessment |
|
| Eosinophilia | Immune system disorders | Systematic Assessment |
|
| Ear Ache post Ear AVM ablation | Ear and labyrinth disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hot Flashes/Night Sweats | General disorders | Systematic Assessment |
|
| Increased INR | Blood and lymphatic system disorders | Systematic Assessment |
|
| Weight Loss | General disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Difficulty Falling Asleep | General disorders | Systematic Assessment |
|
| Increased Creatinine | Renal and urinary disorders | Systematic Assessment |
|
| Disorientation | Nervous system disorders | Systematic Assessment |
|
| Slow Speech | Nervous system disorders | Systematic Assessment |
|
| Asterixis | Nervous system disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment | This adverse event occurred in conjunction with others |
|
| Loss of Appetite | General disorders | Systematic Assessment |
|
| Increase in Aspartate Aminotransferase | Hepatobiliary disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000602 |
| Amino Acids, Peptides, and Proteins |