A Multiple Dose Study to Evaluate Safety, Tolerability, PK, and Efficacy of SER-155 in Adults Undergoing HSCT

Study Overview
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Brief Summary
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An Open-Label and Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of SER-155 in Adults Undergoing Hematopoietic Stem Cell Transplantation to Reduce the Risk of Infection and Graft vs. Host Disease

Detailed Description
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This is a Phase 1b randomized, double-blind, placebo-controlled, multiple dose, multicenter study designed to evaluate the safety, efficacy, and microbiome alterations associated with SER-155 dosing, after microbiome conditioning with oral vancomycin, in adult subjects aged ≥18 years who are undergoing Hematopoietic Stem Cell Transplantation (HSCT).

Official Title
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A Phase 1b Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of SER-155 in Adults Undergoing Hematopoietic Stem Cell Transplantation (HSCT) to Reduce the Risk of Infection and Graft vs. Host Disease (GvHD)

Conditions
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Allogeneic Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Drug: Vancomycin Pre-Treatment
* Drug: Vancomycin Placebo
* Drug: SER-155
* Drug: SER-155 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects ≥ 18 years of age undergoing HSCT. Planning to undergo allogeneic hematopoietic stem cell transplantation from a human leukocyte antigen matched related donor, haploidentical related donor, HLA-matched unrelated donor, or HLA 1-antigen mismatched unrelated or related donor, with either bone marrow or peripheral blood stem cells as a graft source, and with any conditioning regimen Exclusion Criteria: Severe colitis of any etiology or active/currently-treated inflammatory bowel disease (IBD) or total colectomy. Evidence of relapse or progression of hematologic malignancy (minimal residual disease is allowed). Transplant using umbilical cord blood or ex vivo T-cell-depleted HSCT Receipt of chimeric antigen receptor T-cell (CAR-T) therapy. Received a fecal microbiota transplant (FMT) or any live microbial therapeutic within 3 months prior to Screening. Known allergy or intolerance to oral vancomycin. Concomitant participation or participation within 14 days or 5 half-lives of another investigational unapproved treatment, whichever is longer.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There are 2 parts or cohorts for the trial. Cohort 1 is an open-label study. Cohort 2 is double-blind, randomized, placebo-controlled study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - Open Label Study<br>Vancomycin & SER-155 | Drug: Vancomycin Pre-Treatment<br>* Four times daily dosing with Vancomycin<br>Drug: SER-155<br>* Once daily dosing with SER-155<br>|
| Experimental: Cohort 2 - Randomized, Double-Blind, Placebo-Controlled Study<br>Vancomycin & SER-155 OR Vancomycin placebo & SER-155 placebo | Drug: Vancomycin Pre-Treatment<br>* Four times daily dosing with Vancomycin<br>Drug: Vancomycin Placebo<br>* Four times daily dosing with Vancomycin Placebo<br>Drug: SER-155<br>* Once daily dosing with SER-155<br>Drug: SER-155 Placebo<br>* Once daily dosing with SER-155 placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of SER-155, including incidence and severity of adverse events, serious adverse events, or adverse events of special interest | Incidence and severity of participants with adverse events, serious adverse events, or adverse events of special interest | Day 100 | 
| Engraftment of SER-155 | Prevalence of SER-155 strains in subject stool measured before and after treatment courses | Day 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abundance of Enterococcus and Enterobacteriaceae |  | Day 100 | 
| Combined and individual incidence of bloodstream infections, gastrointestinal infections, and acute Graft-versus Host Disease |  | Day 100 | 
| Incidence and duration of febrile neutropenia |  | Day 100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbiome, stem cell transplant