A Study to Evaluate the Safety and Tolerability of Eravacycline in Pediatric Patients Aged 8 to 17 With Complicated Intra-abdominal Infections (cIAI)

Official title

Multicenter, Open-label Trial to Evaluate the Safety and Tolerability of Intravenous Eravacycline in Pediatric Patients From 8 Years to Less Than 18 Years of Age With Complicated Intra-abdominal Infections (cIAI)

Overview

A Phase 2 trial to assess safety, tolerability, and pharmacokinetics of eravacycline in pediatric patients aged 8 to \<18 years with cIAI.

Interventions

• Drug IV Eravacycline 2mg/kg
  infused over a 60-minute period
• Drug IV Eravacycline 1.5mg/kg
  infused over a 60-minute period

Primary outcome measures

• Proportion of patients with Adverse Events (AEs) from the first dose of any amount of eravacycline [Time frame: 28 days]
• Change from baseline values over time in electrocardiogram (ECG) QT measurements [Time frame: Day 28]
• Change from baseline values over time in diastolic blood pressure [Time frame: Day 28]
• Change from baseline values over time in systolic blood pressure [Time frame: Day 28]
• Change from baseline values over time in liver function tests assessed by Comprehensive Metabolic Panel (CMP) [Time frame: Day 28]
• Change from baseline values over time of hemoglobin [Time frame: Day 28]
• Change from baseline values over time in white blood count [Time frame: Day 28]
• Change from baseline values over time in platelets [Time frame: Day 28]
• Change from baseline values over time in kidney function assessed by CMP [Time frame: Day 28]

Secondary outcome measures (2)

• Steady state area under the curve (AUC (0-24)) of eravacycline [Time frame: Dose cycle 4]
• Steady state maximum concentration (Cmax) of eravacycline [Time frame: Dose cycle 4]

Eligibility criteria

Inclusion criteria

• Children from 8 to <18 years of age (as of the day of the informed consent \[and assent, if applicable\] is obtained), hospitalized for cIAI with one of the following diagnoses:

• Intra-abdominal abscess (including hepatic and splenic abscesses).
• Gastric or intestinal perforation associated with diffuse peritonitis.
• Peritonitis: diffuse infection of the peritoneum (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites).
• Appendicitis with perforation, peritonitis, or abscess (complicated appendicitis).
• Cholecystitis with perforation or abscess.
• Patient has one or more systemic signs or symptoms that accompany cIAI, such as fever, leukocytosis, hypotension, abdominal pain, nausea/vomiting, anorexia, abdominal mass on clinical examination, or altered mental status
• Written informed consent from parent(s) or other legally authorized representative(s) and assent (according to local requirements).
• In the investigator's opinion, the patient will require hospitalization for at least 4 days.
• The patient must require hospitalization initially and antibacterial therapy for 4 to 14 days in addition to surgical intervention for the treatment of the current cIAI based on the judgment of the investigator.
• The patient has sufficient intravascular access (peripheral or central) to receive eravacycline.
• The patient meets either (A or B) of the following criteria:

• Pre-operative enrollment:

• i. Has a sonogram or radiographic imaging result consistent with the diagnosis of cIAI, and
• ii. Acute surgical or percutaneous intervention (open laparotomy, laparoscopic surgery, or percutaneous drainage of an abscess) is foreseen within 24 hours.

OR

• Intra-operative/postoperative enrollment:

• i. Visual confirmation of cIAI (presence of pus within the abdominal cavity), and
• ii. Surgical intervention includes open laparotomy, laparoscopic surgery, or percutaneous draining of an abscess, and
• iii. Intervention is considered adequate by the surgical team.

Exclusion criteria

• Patient is considered by the investigator to be unlikely to survive the trial period, and/or has any rapidly progressing disease or immediately life-threatening illness.
• Patient's laboratory test results reveal alanine aminotransferase or aspartate transaminase >5×upper limit of normal range (ULN).
• Patient's laboratory test results reveal total bilirubin >2×ULN, unless isolated hyperbilirubinemia is directly related to the acute process.
• Patient requires peritoneal dialysis, hemodialysis, or hemofiltration at screening. Patient has an estimated glomerular filtration rate (eGFR) <50 mL/minute/1.73 m².
• Patient has previously received eravacycline or have enrolled previously in the current trial and been discontinued.
• Patient has evidence or history of a clinically significant medical condition that may, in the opinion of the investigator, impair trial participation or pose a significant safety risk or diminish the patient's availability to undergo all trial procedures and assessments.
• Patient is likely to require more than 14 days of treatment with eravacycline, in the opinion of the investigator.
• Patient is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days or <5 half-lives of the investigational compound (whichever is longer) prior to screening.
• Patient has immunocompromised condition, including acquired immune deficiency syndrome (AIDS), organ (including bone marrow) transplant recipients, and hematologic malignancy, or receiving immunosuppressive therapy, including cancer chemotherapy, medications for prevention of organ transplantation rejection, or chronic administration of systemic corticosteroids (defined as the systemic equivalent of ≥2 mg/kg total daily dose of prednisone for patients ≤20 kg, or >40 mg of prednisone per day for patients >20 kg, administered continuously for more than 14 days in the 30 days prior to the first dose of eravacycline.
• Patient has known or suspected inflammatory bowel disease.
• Patient has pancreatitis.
• Patient has systemic malignancy that required chemotherapy, immunotherapy, radiation therapy, or antineoplastic therapy within the previous 3 months.
• Patient has history of hypersensitivity or allergic reaction to any tetracycline antibiotics.
• Patient has cIAI caused by a pathogen(s) resistant to eravacycline at screening.
• Patient has received antibacterial drug therapy for continuous duration of >72 hours immediately preceding screening unless they are considered treatment failures. Note: Treatment failure is defined as persistent fever and/or clinical symptoms or the development of a new intra-abdominal abscess after ≥72 hours of antibiotic therapy.
• Patient has received any tetracycline within 14 days of screening.
• Patient used cytochrome P450 (CYP) 3A inducers or inhibitors within 14 days of screening or is receiving or anticipated to need treatment with CYP3A inducers or inhibitors during the treatment period. (The use of a single dose of a moderate or weak CYP3A inducer used within 14 days prior to screening is allowed)
• Patient is currently using or anticipates use of anticoagulant therapy during the treatment period.
• Patient is unable or unwilling, in the opinion of the investigator, to comply with the protocol.
• Patients who are known to be pregnant (positive pregnancy test) and/or breastfeeding at the time of screening.
• Sexually active patients of childbearing potential (those with menarche and/or thelarche) who are unwilling or unable to use an acceptable method of contraception (at least 2 medically accepted, effective methods of birth control \[e.g., condom, oral contraceptive, indwelling intrauterine device, hormonal implant/patch, injections, approved cervical ring\]) or sexual abstinence during study treatment and for 14 days after the last dose of study drug.
• Patient has any other circumstance that, in the opinion of the investigator, precludes the patient's participation in the trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• UCLA Ronald Reagan University of California Los Angeles Medical Center — Los Angeles
• Children's Hospital of Orange County — Orange
• Ann and Robert H Lurie Children's Hospital of Chicago — Chicago
• Children's Hospital of LSU Health Sciences Center Shreveport — Shreveport
• West Virginia University Medicine Children's Hospital — Morgantown

Identifiers

NCT: NCT06794541 · CS434-2023-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗