A Trial of HRS-8427 in the Treatment of Adults With Complicated Urinary Tract Infection, Including Acute Pyelonephritis

Официальное название

A Multi-center, Randomized, Double-blind, Active Controlled, Parallel Groups, Phase III Study to Evaluate the Efficacy and Safety of HRS-8427 in the Treatment of Adults With Complicated Urinary Tract Infection, Including Acute Pyelonephritis

Обзор

The purpose of this study is to evaluate the efficacy and safety of HRS-8427 in patients with complicated urinary tract infection, including acute pyelonephritis.

Вмешательства

• Препарат HRS-8427
  Dosing frequency: for 7-14 days; dose adjustments of subjects with reduced function include reduced doses
• Препарат Imipenem and Cilastatin Sodium
  Dosing frequency: for 7-14 days; dose adjustments of subjects with reduced function include reduced doses
• Препарат HRS-8427 placebo
  Dosing frequency: for 7-14 days; dose adjustments of subjects with reduced function include reduced doses
• Препарат Imipenem and Cilastatin Sodium placebo
  Dosing frequency: for 7-14 days; dose adjustments of subjects with reduced function include reduced doses

Первичные конечные точки

• Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Test of Cure (TOC) [Срок оценки: Test of cure (TOC; 7 days after end of treatment [EOT], equivalent to Study Day 14 to 21)]

Вторичные конечные точки (6)

• Percentage of Participants With Composite Response of Microbiological Eradication and Clinical Response at Early Assessment（EA）、End of Treatment（EOT）and Late Follow-Up (LFU) [Срок оценки: EA : Day 4、EOT: Day 7 to Day 14、LFU：Day 21 to Day 28]
• Percentage of Participants With Microbiological Eradication at EA 、EOT、TOC and LFU [Срок оценки: EA : Day 4、EOT: Day 7 to Day 14、TOC:Day 14 to Day 21、LFU：Day 21 to Day 28]
• Percentage of Participants With Microbiological Eradication at EA 、EOT、TOC and LFU Per Uropathogen [Срок оценки: EA : Day 4、EOT: Day 7 to Day 14、TOC:Day 14 to Day 21、LFU：Day 21 to Day 28]
• Percentage of Participants With Clinical Response at EA 、EOT、TOC and LFU [Срок оценки: EA : Day 4、EOT: Day 7 to Day 14、TOC:Day 14 to Day 21、LFU：Day 21 to Day 28]
• Percentage of Participants With Clinical Response at EA 、EOT、TOC and LFU Per Uropathogen [Срок оценки: EA : Day 4、EOT: Day 7 to Day 14、TOC:Day 14 to Day 21、LFU：Day 21 to Day 28]
• Number of Participants With Adverse Events [Срок оценки: Day 21 to Day 28]

Критерии участия

Критерии включения

• Able and willing to provide a written informed consent before the study, fully understand the study and be able to complete the study according to the protocol;
• Male and female, ≥18 years;
• Judged by the investigator, clinical diagnosis with cUTI or AP, expectation that the patients will require hospitalization and initial treatment with intravenous antibiotics;
• Urine specimen with evidence of pyuria；
• Have urine culture specimen obtained within 48 hours prior to randomization;
• 48 hours before random, allowing a short course of antimicrobial drug treatment is less than 24 hours (random rate ≤25%)
• Women of childbearing potential must have a negative serum pregnancy test before first dose, must be non-lactating. Fertile female subjects or male subjects whose partner is a fertile female agree to use highly effective form of contraception, with no plan of birth, sperm/ovum donation from the time of signed ICF till 14 days after end of treatment.

Критерии исключения

• History of significant hypersensitivity or allergic reaction to any β-lactam, or any β-lactamase inhibitors;
• Known history of immune deficiency disease or receive immunocompromising treatment;
• Severe cardiovascular and cerebrovascular diseases with clinical significance and unstable condition or uncontrolled;
• Known or suspected central nervous system disorder or other factors that may predispose to seizures or lower the seizures onset threshold;
• Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy;
• Uncomplicated lower urinary tract infection;
• Suspected or confirmed urinary tract symptoms caused by acute/chronic prostatitis, orchitis, epididymitis or sexually transmitted diseases as determined by medical history and/or physical examination;
• Patients received cancer treatment within 4 weeks before randomization or planned treatment during the study period;
• Systemic antimicrobial therapy other than the investigational drug need to be used during the study period, with the exception of topical or single oral dose of antifungal treatment
• Urinary tract surgery prior to 7 days before randomization or surgery planned during the study period;
• Indwelling catheter or urinary apparatus, the researchers determine drug treatment period cannot be removed;
• Receipt of potentially effective systemic antibacterial therapy for a continuous duration of ≥24 hours during the previous 48 hours prior to the randomization;
• History of pelvis or urinary tract trauma prior to the randomization;
• Patients had severe trauma or received major surgery prior to the randomization;
• Impairment of renal function with estimated glomerular filtration rate or Creatinine Clearance <15 mL/min ;
• Laboratory abnormalities in baseline specimens obtained at screening;
• A QTcF interval prolongation at screening or abnormalities with clinical significance and may cause obvious safety risk to the subjects;
• Known urine culture with at least one Gram-Negative uropathogen at ≥105 colony-forming units(CFU)/mL unsusceptible to Imipenem and Cilastatin Sodium, or only identify Gram-positive uropathogen, or confirmed fungal urinary tract infection with ≥103CFU/mL;
• Likely to require the use of antibiotic drug prevention after treatment;
• Suspected of sepsis, producing life-threatening organ dysfunction;
• Estimated survival within 6 weeks or rapidly progressive or end stage disease with high mortality rate;
• Drug abuse prior to the randomization;
• Participated in a previous clinical study related to HRS-8427 and used HRS-8427 or have participated in another clinical study within 4 weeks before randomization and used a study drug containing the active ingredient;
• Judgment of the Investigator, other reasons unsuitable for study.

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Huashan Hospital — Шанхай

Публикации

• Yin T, Qu B, Zhang Q, Xu S, Wu Y, Jiang H, Huang Y, Hu W. Pharmacokinetics, safety, and tolerability of HRS-8427, a novel anti-carbapenem-resistant cephalosporin, in healthy subjects. Antimicrob Agents Chemother. 2026 Apr;70(4):e0069425. doi: 10.1128/aac.00694-25. Epub 2026 Mar 3. PMID 41773934
• Wu Y, Han Q, Yang H, Xue J, Wang L, Mao X, Yin T, Jiang H, Xu S, Huang Y, Wang T, He Y, Luo Y, Chen W, Zhang J. Effects of renal impairment and hemodialysis on the pharmacokinetics and safety of HRS-8427, a siderophore cephalosporin for Gram-negative bacterial infections. Antimicrob Agents Chemother. 2026 Feb 4;70(2):e0109525. doi: 10.1128/aac.01095-25. Epub 2026 Jan 13. PMID 41528248
• Cao Y, Huang Y, Xie J, Wu Q, Yang S, Yang X, Huang J, Liu J, Meng J, Yang G. Intrapulmonary penetration and pharmacokinetics of siderophore cephalosporin HRS-8427 injection in Chinese healthy subjects. Antimicrob Agents Chemother. 2025 Dec 10;69(12):e0070225. doi: 10.1128/aac.00702-25. Epub 2025 Nov 6. PMID 41196282

Идентификаторы

NCT: NCT06569056 · HRS-8427-302

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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