Phase 1b/2a Randomized Double-blind Study to Investigate Safety Tolerability PK PD Preliminary Efficacy of Oral Administration of SNIPR001 in Patients With Hematologic Malignancy Scheduled for Allogeneic Hematopoietic Stem-Cell Transplant Receiving FQ Prophylaxis & Harboring FQR Ecoli Pre-Transplant

Официальное название

A Phase 1b/2a, Randomized, Double-blind Study to Investigate Safety, Tolerability, PK, PD, and Preliminary Efficacy of Oral Administration of SNIPR001 in Patients With Hematologic Malignancy Scheduled for Allogeneic Hematopoietic Stem-Cell Transplantation Receiving Fluoroquinolone Prophylaxis and Harboring Fluoroquinolone-Resistant Escherichia Coli Pre-Transplant

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат SNIPR001 consists of genetically modified bacteriophages specifically targeting Escherichia coli
  SNIPR001 is a live biotherapeutic product
• Другое Placebo 10 mL
  Placebo 10 mL matching to SNIPR001 will be administered.

Первичные конечные точки

• 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 [Срок оценки: Day 30 and 100 for endpoints 1-7 and 1-2 weeks for endpoint 8]

Вторичные конечные точки (5)

• To assess the pharmacodynamics (PD) of SNIPR001 in all patients who receive SNIPR001 or placebo in combination with SoC levofloxacin prophylaxis [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: From the first dose of randomized treatment through 30 days after transplant.]

Критерии участия

Критерии включения

• 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.
• Patient is scheduled to receive fluoroquinolone (levofloxacin) prophylaxis.
• Colonized with Fluoroquinolone resistant E. coli (patients will be pre-screened for the presence of at least 1 Fluoroquinolone resistant E. coli colony \[cultured from a perianal swab\] performed at the local hospital lab, qualitative assessment +/-).
• Female patients must be of non-childbearing potential (surgically sterile or menopausal for at least 1 year) or agree to use a highly effective contraception method, per local standard, while receiving treatment with SNIPR001 and for 28 days after the last dose of SNIPR001. Male patients must utilize highly effective contraceptive precautions for the duration of SNIPR001 dosing and for 28 days after the last dose of SNIPR001.
• Female patients of childbearing potential must have a negative serum pregnancy test at Screening and a negative serum or urine test on Day -2 prior to SNIPR001 dosing.
• Are willing to comply with all scheduled visits, laboratory tests, and other study procedures, including drinking the study medications, in the opinion of the Investigator.

Критерии исключения

• 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 Gold treatment.
• Unwilling or unable to comply with the requirements of this Protocol, including providing stool samples.
• Female patients who are pregnant or lactating.
• Have abnormal liver enzymes (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] >2 × upper limit of normal \[ULN\] or total bilirubin >1.5 × ULN).
• Have hepatic disease associated with impaired liver function.
• Have a history of Achilles tendinopathy or tendon rupture.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Профилактика

Центры проведения

США · 8 центров

• City of Hope — Duarte
• University of California, San Francisco — San Francisco
• John Hopkins University — Baltimore
• University of Minnesota — Minneapolis
• Weill Cornell Medicine — New York
• UPMC — Pittsburgh
• University of Texas MD Anderson Cancer Center — Houston
• Fred Hutchinson Cancer Center — Seattle

Идентификаторы

NCT: NCT06938867 · SNIPR001-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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