NCT06938867招募中1 期
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
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 8
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 SNIPR
- •Male patients must utilize highly effective contraceptive precautions for the duration of SNIPR001 dosing and for 28 days after the last dose of SNIPR
- •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.
排除标准
- •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.
研究组 & 干预措施
SNIPR001 Active
Active Comparator
12 patients on SNIPR001 (BID for up to 30 days)
干预措施: SNIPR001 consists of genetically modified bacteriophages specifically targeting Escherichia coli (Biological)
Placebo
Placebo Comparator
12 patients on Placebo (BID for up to 30 days)
干预措施: Placebo 10 mL (Other)
结局指标
主要结局
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
时间窗: Day 30 and 100 for endpoints 1-7 and 1-2 weeks for endpoint 8
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
次要结局
- To assess the pharmacodynamics (PD) of SNIPR001 in all patients who receive SNIPR001 or placebo in combination with SoC levofloxacin prophylaxis(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(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(From the first dose of randomized treatment through 30 days after transplant.)
研究者
研究点 (8)
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相关资讯
Expanded Access Case Report Shows SNIPR001, an Engineered CRISPR Phage Therapy, Associated with 89% Reduction in Multidrug-Resistant E. coli Malakoplakia Mass- A kidney transplant recipient with progressive, multidrug-resistant E. coli malakoplakia received SNIPR001 via intravenous, topical, and intralesional routes under an FDA emergency IND, with no phage-related adverse events reported.
- The intra-abdominal malakoplakia mass decreased from 745 cm³ at baseline to 82 cm³ at one year, an 89% reduction, and follow-up urine and tissue cultures were negative following treatment.
- SNIPR001 is a CRISPR-armed phage therapeutic designed to selectively target E. coli; it is currently in Phase 1b/2a development for preventing bloodstream infections in hematological cancer patients and holds FDA Fast Track designation.
- The case supports further investigation of non-oral delivery for infections outside the gut, though causality cannot be attributed solely to SNIPR001 given concomitant antibiotic therapy.last monthSNIPR's CRISPR-Armed Phage Therapy SNIPR001 Demonstrates Safety in First Human Trial- SNIPR Biome published positive Phase 1 results for SNIPR001 in The Lancet Microbe, marking the first randomized, placebo-controlled trial of an orally administered CRISPR-Cas-armed bacteriophage therapeutic.
- The study demonstrated favorable safety and tolerability across three dose levels in 36 healthy volunteers, with no serious adverse events and restriction to the gastrointestinal tract without systemic exposure.
- SNIPR001 showed a 78% reduction in E. coli levels versus placebo at the highest dose, though the study was not powered for statistical significance on efficacy endpoints.
- The company's ongoing Phase 1b trial in hematological cancer patients undergoing stem-cell transplantation is now more than halfway complete, targeting a high-risk population prone to antibiotic-resistant bloodstream infections.6 months agoSNIPR Biome Doses First Patient with CRISPR-Armed Phage Therapy SNIPR001 for Drug-Resistant E. coli Prevention- SNIPR Biome has dosed the first patient in its Phase 1b trial of SNIPR001, a CRISPR-armed phage therapy targeting fluoroquinolone-resistant E. coli in hematological cancer patients undergoing stem cell transplantation.
- The therapy combines four engineered bacteriophages that specifically target drug-resistant E. coli in the gut microbiome while preserving beneficial bacteria, addressing a critical unmet need in cancer care.
- The randomized, double-blind, placebo-controlled trial will evaluate safety, tolerability, and efficacy in 24 patients across eight US centers, building on promising Phase 1a safety data in healthy volunteers.
- E. coli causes 25-30% of bacteremia cases in neutropenic hematological cancer patients, with up to 65% showing fluoroquinolone resistance, making this precision approach potentially transformative for vulnerable patient populations.last year