KRT-232 in Subjects With PMF Post-PV MF or Post-ET MF Who Have Failed a JAK Inhibitor

  • STATUS
    Recruiting
  • End date
    Feb 28, 2023
  • participants needed
    203
  • sponsor
    Kartos Therapeutics, Inc.
Updated on 23 January 2021

Summary

This study evaluates the efficacy in achieving clinical cure in non-bacteremic urinary tract infections (UTI) caused by Escherichia coli or Klebsiella pneumoniae producers of extended-spectrum -lactamases (ESBL) in adult patients. Half of participants will receive Piperacillin/Tazobactam as treatment, while the other half will receive Carbapenems.

The investigators will verify that Piperacillin/Tazobactam is not inferior in achieving clinical cure, and that is not associated with a higher risk of adverse events in the directed treatment of non-bacteremic UTI compared to Carbapenems.

The researchers hope to improve the use of antibiotics in the non-bacteremic UTI, reducing the "collateral damage" related to a deterioration in the prognosis of patients and the generation of resistant germs caused by the use of broad-spectrum antibiotics as carbapenems.

Description

Urinary tract infection (UTI) is a common cause of hospitalization worldwide, the prevalence throughout the life of UTI has been reported in about 50,000 cases per 100,000 women and 13,000 per 100,000 men in the United States. Hospitalization for community-acquired UTI is about 33%. Furthermore, the UTI related to bladder catheterization during hospitalization is the most common type of infection acquired, representing 40% of all nosocomial infections. UTI hospitalization is associated with a high cost to the healthcare system.

The diagnosis of UTI is based on demonstrating the presence of bacteria urine in patients with suggestive clinical manifestations and verifying the host's inflammatory response to infection. The most common etiological agents include Escherichia coli, Klebsiella spp, and Proteus spp, with different prevalence and antibiotic susceptibility profiles among different populations.

Currently the appropriate treatment of UTI is a growing concern in the medical community because Gram-negative, specifically Enterobacteriaceae, bacteria have acquired genes encoding antibiotic resistance mechanisms. The -lactamase spread spectrum (ESBL) are documented with increasing frequency among microorganisms causing UTI. Current treatment options for ESBL bacteria include nitrofurantoin, fosfomycin, piperacillin-tazobactam, carbapenems, and aminoglycosides.

Carbapenems and piperacillin-tazobactam are antibiotics used in medical practice for many years, both therapies are licensed for the treatment of non-bacteremic UTI; however, so far there is not enough evidence to discriminate the best choice for the treatment of non-bacteremic UTI (although carbapenems are considered drugs of choice for infections caused by these microorganisms), but carbapenems use has been associated with an increased risk of "collateral damage" related to the generation of resistant germs.

The investigators will compare between piperacillin/tazobactam and carbapenems the effectiveness in achieving clinical cure for non-bacteremic UTI caused by ESBL microorganisms. Researchers principal hypothesis is that Piperacillin/tazobactam is not inferior to carbapenems in achieving clinical cure in the targeted treatment of UTI caused by non-bacteremic due to E. coli or K. pneumoniae ESBL in adults requiring hospitalization. Researchers will verify too if Piperacillin/Tazobactam is not associated with increased risk of adverse events during the targeted treatment of non-bacteremic ITU caused by E. coli or K. pneumoniae ESBL in adults requiring hospital admission, compared with Carbapenems therapy.

To perform the protocol researchers follows the recommendations for the design of trials investigating treatment options for resistant bacteria multidrug (Uncomplicated Urinary Tract Infections: Developing Drugs for Treatment) of the United States Agency for Food and Drug Administration (FDA).

Participants will be included in the study with informed consent. The study variables will be obtained by patient interview and review of medical history. Variables will be recorded in a computerized database developed specifically for this study, with exclusive access for the researchers.

The estimated project duration is 2 years expected to begin in april of 2019.

Details
Condition Myelosclerosis with myeloid metaplasia, Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Myelofibrosis, Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF), Post-Polycythemia Vera MF (Post-PV-MF), Post-Essential Thrombocythemia MF (Post-ET-MF)
Treatment KRT-232
Clinical Study IdentifierNCT03662126
SponsorKartos Therapeutics, Inc.
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Post-Polycythemia Vera MF (Post-PV-MF) or Post-Essential Thrombocythemia MF (Post-ET-MF) or Myelosclerosis with myeloid metaplasia?
Do you have any of these conditions: Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post-Polycythemia Vera MF (Post-PV-MF) or Post-Essential Thrombocythemia MF (Post-ET-MF)?
Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
Failure of prior treatment with JAK inhibitor (Part A) or ruxolitinib (Part B)
ECOG 2

Exclusion Criteria

Prior splenectomy
Splenic irradiation within 3 months prior to the first dose of KRT-232
Active or chronic bleeding within 4 weeks prior to the first dose of KRT-232
Prior MDM2 inhibitor therapy or p53-directed therapy
Prior treatment with HDAC or BCL-2 inhibitors
Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)
Clear my responses

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