2024-516360-29-00招募中2 期
A Multi-Center, Open-Label, Single-Arm, Phase 2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Vabomere (meropenem-vaborbactam) in the Treatment of Children with Complicated Urinary Tract Infection, Including Acute Pyelonephritis
Rempex Pharmaceuticals Inc.24 个研究点 分布在 6 个国家目标入组 36 人开始时间: 2025年3月18日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 24
- 主要终点
- Safety and tolerability based on adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), clinical laboratory (hematology, clinical chemistry, and urinalysis) changes from baseline, and vital sign changes from baseline
研究概览
简要总结
To assess the safety and tolerability of Vabomere administered by intravenous (IV) infusion in children ≥ 3 months to < 12 years with cUTI, including AP.
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Male or female, aged ≥ 3 months to < 12 years of age. Patients aged ≥ 3 months to < 1 year must have been born at term (defined as gestational age > 37 weeks)
- •Written informed consent from parent(s) or legally acceptable representative(s), and informed assent from subject (if age appropriate according to the local regulations) before initiation of any study-related procedures;
- •Have a clinically suspected and/or bacteriologically documented cUTI or AP judged by the Investigator that requires subject to be hospitalized for treatment with at least 3 days of IV antibiotics;
- •Evidence of pyuria, confirmed by either of the following: a. A urine specimen that is positive for leukocyte esterase via urine dipstick or urinalysis, or b. A urine specimen with either > 10 WBCs per microliter from an unspun urine or > 5 WBCs per high power field from a centrifuged specimen;
- •Symptomatic or asymptomatic cUTI or AP as designated by the following clinical signs and symptoms. Symptomatic cUTI If 2 years of age or older, the subject must have at least TWO of the following signs and symptoms: • Fever (oral temp. > 38.0° C, tympanic temp. > 38.3° C, or rectal or core temperature > 38.8° C) • Dysuria • Increased urinary frequency • Urgency • Suprapubic, flank, or abdominal pain • Secondary urinary incontinence • Nausea or vomiting If less than 2 years of age, the subject must have at least TWO of the following: • Fever (oral temp. > 38.0° C, tympanic temp. > 38.3° C, or rectal or core temp. > 38.8° C) • Failure to thrive • Recent weight loss • Irritability • Jaundice • Abdominal tenderness • Vomiting • Poor feeding • Lethargy AND • Have at least ONE complicating factor as listed below (Complicating Factors); Asymptomatic cUTI • Must be unable to perceive symptoms of UTI due to congenital and acquired spinal cord injury or abnormality AND • Have at least ONE complicating factor as listed below (Complicating Factors); Complicating Factors • Indwelling urinary catheter or other indwelling urinary tract instrumentation that is anticipated to be removed during the course of IV study therapy; • Use of intermittent urinary catheterization; • Urogenital surgery within the 7 days before administration of the first dose of IV study drug; • Known functional or anatomic abnormality of the urogenital tract; • Obstructive uropathy where the obstruction is likely to resolve or be relieved during IV study drug therapy administration; • Previously documented vesicoureteral reflux; • Neurogenic disturbance of micturition with significant impact on bladder emptying, with bladder residual volume ≥ 50 mL for children weighing < 40 kg and ≥ 100 mL for children weighing ≥ 40 kg, as previously determined by voiding cystourethrogram (VCUG), ultrasound, or urinary catheterization immediately post void; • Recurrent UTI (defined as 2 or more previous UTIs within a 12-month period)); • Evidence that the current UTI may be caused by a resistant organism, including a suspected breakthrough infection in a child receiving chronic antimicrobial prophylaxis for the prevention of UTI; • Prior documentation of congenital structural or functional urologic abnormality, including but not limited to findings from prenatal or postnatal ultrasound or postnatal VCUG; Acute Pyelonephritis Subjects enrolled with a diagnosis of AP must have both: • Evidence of systemic inflammatory response as demonstrated by at least ONE of the following: • Fever (oral temp. > 38.0° C, tympanic temp. >38.3° C, or rectal or core temp. >38.8° C) or hypothermia (rectal or core temp. <35.0° C) • Leukocytosis, defined as WBC > 15,000 cells/μL OR > 15% immature neutrophils, regardless of the total peripheral WBC count • C-reactive protein ≥ 20 mg/L AND • At least ONE of the following signs or symptoms: • Nausea • Vomiting • Chills • Dysuria • Increased urinary frequency • Urgency • Lower back or flank pain or costovertebral angle tenderness;
- •Have a pretreatment “baseline” urine specimen obtained for culture by an acceptable method, including suprapubic aspiration (SPA), clean urethral catheterization, indwelling urethral catheter, or mid-stream clean catch (urine specimens obtained from externally placed urine bags will not be allowed) within 48 hours before the start of the administration of the first dose of IV study drug therapy. Note: subjects who are not able to perceive symptoms of UTI due to congenital or acquired spinal cord injury or abnormality and are enrolled with the diagnosis of ”asymptomatic cUTI” are required to provide 2 baseline urine cultures from urine specimens obtained at least 1 hour apart. If enrolled as asymptomatic cUTI, both baseline urine cultures must return positive results of an appropriate gram-negative organism;
- •Must, based on the judgment of the Investigator, require hospitalization initially and 7 to 14 days of antibacterial therapy for the treatment of the presumed cUTI. Note: the subject must be anticipated to require at least 3 days of IV antibiotic therapy initially;
- •Females of childbearing potential who have reached menarche or Tanner stage 3 must agree to sexual abstinence or use of a highly effective (≥ 99% effective) form of contraception from the time of screening until 7 days after the end of study treatment Note: effectiveness of hormonal contraceptives may be reduced with Vabomere coadministration, and therefore should not be considered an effective method of contraception;
- •Males who have reached Tanner stage 3 must be willing to practice abstinence or use a highly effective method of birth control from the time of screening until 7 days after the end of study treatment.
排除标准
- •History of hypersensitivity or allergic reaction to beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, monobactams);
- •Subjects undergoing dialysis or with eGFR < 30 ml/min/1.73m2, as calculated using the updated bedside Schwartz formula: eGFR = k × (height in cm) ÷ serum creatinine, where k = 0.45 in term infants to 1 year of age, k = 0.55 in children > 1 year of age;
- •Treatment within 30 days prior to enrollment with valproic acid or probenecid;
- •Evidence of significant hepatic disease or dysfunction, including known acute viral or inactive chronic hepatitis or hepatic encephalopathy, or aspartate aminotransferase or alanine aminotransferase > 3 × upper limit normal (ULN), or total bilirubin > 1.5 × ULN;
- •Immunodeficiency or an immunocompromised condition, including hematologic malignancy, bone marrow transplant, or receiving immunosuppressive therapy such as cancer chemotherapy, medication for the rejection of transplantation, and long-term use of systemic corticosteroids (equivalent to ≥ 20 mg a day of prednisone or systemic equivalent for ≥ 2 weeks);
- •Receipt of any investigational medication or investigational device during the last 30 days or during 5 half-lives of an investigational medication, whichever is longer, prior to enrollment;
- •Requirement at time of enrollment for any reason for additional systemic antibiotic therapy (other than study drug) or systemic antifungal therapy;
- •Known history of human immunodeficiency virus infection, with a CD4 count < 200/mm3;
- •Presence of neutropenia (< 500 polymorphonuclear leukocytes [PMNs]/mm3);
- •Presence of thrombocytopenia (< 60,000 platelets/mm3);
- •Presence of any of the following conditions: • Perinephric abscess, • Renal corticomedullary abscess, • Uncomplicated cystitis, • Polycystic kidney disease, • Previous or planned renal transplantation, • Subjects receiving hemodialysis, • Previous or planned cystectomy or ileal loop surgery or pelvic trauma with urinary tract damage, or • Known candiduria at the time of the cUTI/AP diagnosis;
- •Known Vabomere-resistant gram-negative organism from studyqualifying urine or blood culture, confirmed cUTI or AP only due to gram-positive organism from study-qualifying urine or blood culture, or known or suspected infection with organisms that are not adequately covered by Vabomere (e.g., viral, mycobacterial, fungal) Note: if determined after enrollment, the subject may remain on study drug at the Investigator’s discretion;
- •Gross hematuria requiring intervention other than administration of study drug;
- •Known non-renal source of infection such as endocarditis, osteomyelitis, abscess, meningitis, C. difficile infection, or pneumonia diagnosed within 7 days prior to enrollment
- •Unable or unwilling, in the judgment of the Investigator, to comply with the protocol or complete the clinical study (e.g., unlikely to survive 28 days from initiation of Study Drug);
- •An employee of the Investigator or study center with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, or a family member of the employee or the Investigator;
- •Receipt of a potentially effective antibacterial drug therapy for cUTI for a continuous duration of more than 24 hours during the previous 72 hours prior to enrollment. Exceptions: subjects with unequivocal clinical evidence of treatment failure (i.e., worsening signs and symptoms), urine culture confirms resistance to the initial antibiotic, or the subject developed signs and symptoms of cUTI or AP while on antibiotics for another indication;
- •BMI outside the range (below the 5th percentile or above the 95th percentile) for subject’s age;
- •Any surgical or medical condition which, in the opinion of the Investigator, would put the subject at increased risk or is likely to interfere with study procedures or PK of the study drug;
- •Known or suspected nervous system disorder that suggests a predisposition to seizures, including febrile seizures in the previous 12 months;
- •Pregnant or breastfeeding female adolescent subjects with a positive serum or high-sensitivity urine β human chorionic gonadotropin (hCG) pregnancy test at Screening; If pregnancy test results are not yet available prior to the first dose of study treatment, a highsensitivity urine test may be performed; subjects with a positive hCG result must be withdrawn from the study;
结局指标
主要结局
Safety and tolerability based on adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), clinical laboratory (hematology, clinical chemistry, and urinalysis) changes from baseline, and vital sign changes from baseline
Safety and tolerability based on adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), clinical laboratory (hematology, clinical chemistry, and urinalysis) changes from baseline, and vital sign changes from baseline
次要结局
- 1. PK: - Plasma from each blood draw will be used to estimate population PK parameters, including Cmax, Cmin, Tmax, t1/2, AUC0-8, AUC0-inf, Vss, Vz, and CL for meropenem and vaborbactam
- 2. Efficacy: o Overall response (combined per-subject clinical cure and favorable microbiological response, as defined below) o Clinical cure: complete resolution or significant improvement of signs and symptoms of cUTI or AP present at baseline, no new symptoms, and subject is alive
- 3. Efficacy: o Favorable microbiological response (microbiological eradication): reduction of baseline pathogen(s) (< 10^3 CFU/mL and at least 1-log reduction from baseline) or negative urine culture, negative repeated blood culture if blood culture was positive for pathogen(s) growth at baseline, and subject is alive
研究者
Daniel Selig
Scientific
Rempex Pharmaceuticals Inc.
研究点 (24)
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