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. The study consists of two parts. Part 1 will include 24 randomized and dosed patients. Part 2 will be added with amendment 3 and will include 42 randomized and dosed patients. Thus, approximately 66 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.
Male or female ≥18 years of age at the time of consent.
Patient is able and willing to provide written informed consent prior to any study-related procedure.
Confirmed diagnosis of any hematologic malignancy.
Planned to undergo an allogeneic hematopoietic stem cell transplant.
Use of any treatment (approved or investigational product) considered to interact with the study drug, or which might impact the outcome of the study within 14 days (or 5 half-lives of the approved or investigational product, whichever is greater) prior to the first administration of study drug, as judged by the Investigator.
Use or planned use of any antibiotics with intrinsic activity against E. coli in the gut (e.g., beta-lactam antibiotics) between Pre-Screening and until the end of the SNIPR001/placebo treatment period, with the exception of TMP-SMX and levofloxacin.
Have known hypersensitivity or allergy to any component of SNIPR001, levofloxacin and/or Alka-Seltzer treatment.
Unwilling or unable to comply with the requirements of this Protocol, including providing stool samples.
Parallel
SNIPR001 consists of genetically modified bacteriophages specifically targeting Escherichia coli
Biological/VaccineSNIPR001 is a live biotherapeutic product
Placebo 10 mL
Other interventionPlacebo 10 mL matching to SNIPR001 will be administered.
To 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
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
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
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
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.
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SNIPR Biome Aps.
Lead sponsor
U.S. Health and Human Services and Biomedical Advanced Research and Development Authority
Collaborator
The European Commission's DG Health Emergency Preparedness and Response Authority (DG HERA) and KfW Development Bank
Collaborator
Italy's Ministry of Economy and Finance
Collaborator
CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator)
Collaborator
Wellcome Trust
Collaborator
Novo Nordisk Foundation
Collaborator
