A Double-blinded, Parallel-group, Randomized, Active-controlled Phase 2 Clinical Trial to Assess the Safety, Tolerability, Efficacy, and Pharmacokinetics of Intravenous HY-001 Versus Standard Colistin Methanesulfonate Sodium Monotherapy in Patients with Complicated Urinary Tract Infection (with or without pyelonephritis) or Acute Uncomplicated Pyelonephritis at Risk for Infection with Multidrug Resistant Gram-negative Pathogens.
- Conditions
- complicated urinary tract infection (cUTI).MedDRA version: 20.0Level: HLTClassification code 10046577Term: Urinary tract infectionsSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2019-000910-12-PL
- Lead Sponsor
- Helperby Therapeutics Ireland Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 28
1. Hospitalised patients with cUTI (with or without pyelonephritis) or AP at risk for infection with MDR Gram-negative pathogens, and who have provided written informed consent and willing and able to comply with all study procedures and activities
2. Patients who could receive CMS treatment as part of their standard care
3. Age =18 years and <80 years of age
4. BMI =18 to < 30 kg/m2
5. Patients who have a positive urine culture obtained within 48 hours before randomization containing =10^5 CFU/mL of a Gram-negative uropathogen are eligible for the study.
a. Patients may be enrolled before the results of the urine culture are available and treatment should NOT be delayed pending urine culture results
b. Patients with pathogens resistant or intermediate susceptible to colistin may continue to receive study drug upon the best clinical judgment of the Investigator
c. Patients who have a concomitant infection at the time of randomization that requires nonstudy systemic Gram-positive antibacterial therapy (medication with only Gram-positive activity [eg, vancomycin, daptomycin, linezolid] in addition to IV study drug, are allowed
6. Must have cUTI or acute complicated or uncomplicated pyelonephritis and must have =2 of the following acute signs and symptoms:
a. Chills or rigors or warmth associated with fever (eg. oral or tympanic temperature >38.0 C)
b. Flank pain (pyelonephritis) or pelvic pain
c. Nausea or vomiting
d. Dysuria, urinary frequency, or urinary urgency
e. Costo-vertebral angle tenderness (pyelonephritis) on physical examination
7. Provide a pretreatment adequate urine sample (the urine sample must return a positive culture for the patient to remain eligible for the study) obtained before administration of study drug or administration of any potentially effective antibiotic therapy against Gram-negative pathogens. A positive urine culture is defined as =10^5 CFU/mL of a causative uropathogen
a. If the patient’s pretreatment culture shows the presence of a colistin resistant or colistin intermediate susceptible pathogens after the patient has been enrolled, the Investigator must decide according to clinical signs and symptoms whether the patient can remain in the study
b. In the event of a negative urine culture, the patient must be prematurely discontinued from study drug and switched to standard-of-care treatment. A negative urine culture is one in which a pathogen with <10^5 CFU/mL is present
c. A urine culture is defined as contaminated if =1 causative pathogen with =10^5 CFU/mL is present AND =1 nonpathogen =10^5 CFU/mL are present
8. Have pyuria (ie, a dipstick analysis positive for leukocyte esterase or =10 white blood cells (WBCs) per cubic millimetre [1 µl]) in unspun urine, or =10 WBCs per high power field in spun urine
9. Be considered ill enough to be hospitalised for =5 days and require the initiation of parenteral therapy to manage cUTI by the standard of care
10. Contraception in women of childbearing potential must have been used for =2 months before starting the study; a documented negative highly sensitive serum pregnancy test must be provided and the patient must be nonlactating
11. If of non-childbearing potential, must be postmenopausal (ie, has had amenorrhea for =12 consecutive months) or surgically sterile for =6 months due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy
12. If of childbearing potential, agree to use a highly effective method of contraception, preferably with low use
1.Patient has a confirmed or suspected fungal or anaerobic UTI, or UTI caused by a Gram-positive pathogen or UTI caused by a pathogen kown or suspected to be intrinsically resistant to colistin;2.Patients with asymptomatic bacteriuria, the presence of >10^5 CFU/mL of a causative pathogen, and pyuria, but without local or systemic symptoms;3.Patient is receiving haemodialysis or peritoneal dialysis or has impairment of renal function including an estimated glomerular filtration rate <60 mL/min using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, requirement for peritoneal dialysis, or haemodialysis or hemofiltration;4.Concurrent use of onstudy systemic antibacterial and antimicrobial drug therapy with Gram-negative activity (including reverse transcriptase inhibitors) that would have a potential effect on outcome evaluations in patients with cUTI;5.Known hypersensitivity to CMS, colistin, other polymyxins, or zidovudine; 6.Uncomplicated cystitis in females;7.Having ileal loops, urinary diversion with bowel segments or suspected or confirmed vesicoureteral reflux, suspected or confirmed perinephric or intrarenal abscess; 8.History of renal transplant, any permanent complicating factors of the urinary tract that cannot be effectively treated during the therapy of the infection; 9.Indwelling urinary catheters expected to remain in place after therapy has been completed; 10.Any contraindication to the treatment with the individual medications according to the registered label; 11.Any infection that, in the opinion of the Investigator, would be considered intractable and likely to require >14 days of study drug;12.Any patient receiving a long-acting antibiotic with potentially effective Gram-negative activity or >1 dose of any antibiotic with potentially effective Gram-negative activity, within 72 hours before the first dose of study drug; 13.Previous participation in a clinical trial or treatment with investigational medication within the last 4 weeks or =5 half-lives, whichever is shorter, before starting study drug or patients who have not recovered from side effects of such investigational therapy; 14.Significantly immunocompromised (defined as a WBC <1000/µL) and/or having a known infection with human immunodeficiency virus (HIV);15.Any haematological malignancy, bone marrow transplantation, or current immunosuppressive therapy (including but not limited to cancer chemotherapy, or medications for prevention of organ transplantation rejection) or current treatment with reverse transcriptase inhibitors with Gram-negative activity; 16.Any concomitant psychiatric, neurological, or behavioural disorder including epilepsy or other lesions of the central nervous system sufficient in the opinion of the Investigator to prevent or compromise the patient’s participation in the study; 17.Any known concomitant bacterial or fungal sexually transmitted disease, except for candidiasis; 18.Having, in the opinion of the Investigator, any clinically significant serious or unstable physical illness likely to impact on the patient’s wellbeing or the conduct and analysis of the study, including, but not limited to, acute hepatic failure, respiratory failure, severe, persistent diarrhoea and septic shock; 19.Any malignant disease or a history of malignant neoplasm requiring a treatment with immune suppressive properties in the past 6 months before baseline; 20.Known history of drug or alcohol abuse; 21.Clinically significant abno
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method