This is a Phase 1b/2a study in allogenic hematopoietic stem cell transplant patients to investigate the safety, PK, PD and preliminary efficacy of multiple oral administrations of SNIPR001 when given concomitantly with SoC levofloxacin.
Patients scheduled for allo-HSCT will be pre-screened for the presence (in the gut) of FQR E. coli cultured from a perianal swab. Approximately 24 patients will be randomized 1:1 to oral dosing of SNIPR001 or matching placebo, to be taken concomitantly with SoC levofloxacin prophylaxis. Subjects will be followed until 100 days post allo-HSCT transplant.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
24
SNIPR001 is a live biotherapeutic product
Placebo 10 mL matching to SNIPR001 will be administered.
City of Hope
Duarte, California, United States
RECRUITINGUniversity of California, San Francisco
San Francisco, California, United States
RECRUITINGJohn Hopkins University
Baltimore, Maryland, United States
RECRUITINGUniversity of Minnesota
Minneapolis, Minnesota, United States
RECRUITINGWeill Cornell Medicine
New York, New York, United States
RECRUITINGUPMC
Pittsburgh, Pennsylvania, United States
RECRUITINGUniversity of Texas MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGFred Hutchinson Cancer Center
Seattle, Washington, United States
RECRUITINGTo assess the safety and tolerability of SNIPR001 in all patients who receive SNIPR001 or placebo in combination with standard of care (SoC) levofloxacin prophylaxis
1. Incidence and severity of adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs), based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 5 (NCI CTCAE v5.0). AEs involving graft versus host disease (GvHD) will be graded according to the International Bone Marrow Registry Severity Index. 2. Time to neutrophil recovery (defined as the 1st day of ANC ≥0.5x109/L for 3 consecutive days) 3. Incidence of non-relapse mortality (NRM) 4. Incidence of all-cause mortality 5. Incidence of primary graft failure and secondary graft failure 6. Incidence of acute graft versus host disease (aGvHD) 7. Incidence of Clostridioides difficile (C. difficile) diarrhea 8. Median number of days from transplant to onset of neutropenic fever
Time frame: Day 30 and 100 for endpoints 1-7 and 1-2 weeks for endpoint 8
To assess the pharmacodynamics (PD) of SNIPR001 in all patients who receive SNIPR001 or placebo in combination with SoC levofloxacin prophylaxis
Proportion of patients with an increase in E. coli relative abundance in stool
Time frame: Baseline and last day of dosing
To assess the pharmacodynamics (PD) of SNIPR001 in all patients who receive SNIPR001 or placebo in combination with SoC levofloxacin prophylaxis
Change in E. coli relative abundance in stool
Time frame: Day-2 to end of dosing
To assess the pharmacodynamics (PD) of SNIPR001 in all patients who receive SNIPR001 or placebo in combination with SoC levofloxacin prophylaxis
Change in E. coli absolute abundance
Time frame: Day-2 to end of dosing
To assess the pharmacokinetics (PK) of SNIPR001 in all patients who receive SNIPR001 or placebo in combination with SoC levofloxacin prophylaxis
Recovery of SNIPR001 from first dose of randomized treatment through 7 days after last dose randomized treatment in stool, blood and urine based on the number of plaque-forming units (PFUs) per gram in stool, and the number of PFUs per milliliter in blood and urine.
Time frame: From first dose of randomized treatment through 7 days after last dose of randomized treatment in stool, blood and urine
To assess the preliminary efficacy of SNIPR001 in all patients who receive SNIPR001 or placebo in combination with SoC levofloxacin prophylaxis
* Proportion of patients with E. coli bloodstream infections (BSIs) assessed from the first dose of randomized treatment through 30 days after transplant. * Proportion of patients with gram-negative BSIs only, assessed from first dose of randomized treatment through 30 days after transplant. * Proportion of patients with gram-positive BSIs only, assessed from first dose of randomized treatment through 30 days after transplant. * Total BSIs assessed from first dose of randomized treatment through 30 days after transplant. * Incidence and number of neutropenic fever episodes from first dose of randomized treatment through 30 days after transplant. * Incidence and number of patients receiving broad-spectrum antibiotics on suspicion of a bloodstream infection
Time frame: From the first dose of randomized treatment through 30 days after transplant.
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