A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CAL02 ADMINISTERED INTRAVENOUSLY IN ADDITION TO STANDARD OF CARE IN SUBJECTS WITH SEVERE COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA (SCABP)
- Trial ID
- 2022-502049-91-00
- Protocol
- EGL-6535-C-2202
- Sponsor
- Eagle Pharmaceuticals Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **CAL02** administration on clinical recovery in subjects with severe community-acquired bacterial pneumonia (SCABP) compared to placebo. Additionally, the study aims to assess the safety and tolerability of CAL02 versus placebo. This is clinically relevant as it addresses the potential of CAL02 to enhance recovery outcomes and ensure patient safety in a severe infectious condition.
Secondary objectives include:
- Evaluating the effect of CAL02 administration on the duration of critical care management compared to placebo.
- Assessing the impact of CAL02 on the duration of overall hospital stay compared to placebo.
- Investigating the effect of CAL02 on early clinical recovery by Day 5 compared to placebo.
- Evaluating the effects of CAL02 on SOFA (Sequential Organ Failure Assessment) scores compared to placebo.
Participants
The clinical trial involves a total of **184 participants** diagnosed with **severe community-acquired bacterial pneumonia (SCABP)**. The study population includes both male and female subjects aged 18 years and older, with a body weight ranging from 40 to 140 kg. Participants were selected based on a clinical diagnosis of community-acquired bacterial pneumonia, confirmed within 48 hours of hospital admission, and the presence of specific severity criteria such as respiratory failure requiring mechanical ventilation or septic shock necessitating vasopressor treatment. The trial population is characterized by individuals requiring critical care management for SCABP. Written informed consent was obtained from all participants or their legally acceptable representatives in accordance with local guidelines. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, emphasizing the critical nature of the condition being studied.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of CAL02 administered intravenously in addition to standard care for subjects with severe community-acquired bacterial pneumonia (SCABP). The trial is set to run from July 10, 2023, to October 31, 2024. Participants will be randomly assigned to receive either CAL02 or a placebo, both delivered as a **solution for infusion**. The primary objectives are to assess the effect of CAL02 on clinical recovery and to evaluate its safety and tolerability compared to placebo.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, body weight, and clinical diagnosis of SCABP. Following randomization, participants will receive the investigational product or placebo for a maximum treatment period of two days. Follow-up visits will be conducted to monitor the time to clinical recovery, incidence and severity of treatment-emergent adverse events (TEAEs), and any infusion-related reactions. Secondary endpoints include the time to critical care management discharge, time to hospital discharge, and the proportion of subjects achieving clinical recovery by Day 5.
The expected length of participant involvement is approximately two days for the treatment period, with additional time for follow-up assessments. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or the participant's withdrawal of consent. The study aims to ensure that all severity criteria are resolved without recurrence within 24 hours after recovery, as part of the primary endpoint evaluation. The trial is conducted under strict adherence to ethical guidelines, with informed consent obtained from all participants or their legally acceptable representatives before any study-specific assessments are performed.
Treatment
The clinical trial involves the administration of **CAL02**, a **solution for infusion** developed by Eagle Pharmaceuticals, Inc. This investigational medication contains the active substances **cholesterol** and **sphingomyelin (egg)**. The pharmaceutical form is a solution intended for intravenous infusion. The maximum daily dose is 1920 mg, with a total maximum dose of 3840 mg over a treatment period of up to 2 days. The administration is conducted via intravenous infusion, and the formulation is not specifically designed for pediatric use. Participant compliance is monitored to ensure adherence to the dosing schedule.
In addition to the experimental treatment, the study utilizes **Natriumchloride 0,9%**, a **solution for infusion** produced by Fresenius Kabi Nederland B.V. This non-experimental treatment serves as a placebo in the trial. The active substance in this solution is **sodium chloride**, and it is administered intravenously. The maximum daily dose is 250 ml, with a total maximum dose of 500 ml over a 2-day treatment period. This solution is also not formulated for pediatric use. The administration and dosing schedules are carefully monitored to maintain consistency and ensure the integrity of the trial results.
Efficacy
The efficacy of the investigational medicinal product (IMP) CAL02 in the treatment of severe community-acquired bacterial pneumonia (SCABP) will be assessed through a randomized, double-blind, placebo-controlled multicenter study. The primary endpoints for evaluating efficacy include the time to clinical recovery, defined as the number of days until all severity criteria that met the SCABP definition at randomization, and any new severity criteria occurring post-randomization, are resolved without recurrence within 24 hours. Additionally, the incidence and severity of treatment-emergent adverse events (TEAEs), including infusion-related reactions, and the incidence of interruptions and discontinuations of the IMP intravenous infusion will be monitored.
Secondary endpoints will further assess efficacy by measuring the time to discharge from critical care management and hospital discharge, the proportion of subjects achieving clinical recovery by Day 5, and the relative change from baseline in the whole Sequential Organ Failure Assessment (SOFA) score at Day 7. These parameters will be collected and analyzed at specified timepoints throughout the study to provide a comprehensive evaluation of the treatment's impact on patient recovery and overall health outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Males or females ≥18 years old
- Body weight 40 to 140 kg (88 to 308 lb), inclusive
- Clinical diagnosis of CABP (diagnosed ≤48 hours after hospital admission)
- Presence of at least one of the following severity criteria, based on protocol defined SCABP: a. Respiratory failure requiring invasive mechanical ventilation support b. Respiratory failure requiring non-invasive positive pressure ventilation support (eg, continuous positive airway pressure [C-PAP], bi-level positive airway pressure [Bi-PAP]) and partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) ≤250 mm Hg, excluding home setting non-invasive positive pressure ventilation support c. Respiratory failure requiring high-flow oxygen defined as >40 L/min and PaO2/FiO2 ratio ≤250 mm Hg d. Septic shock requiring treatment with vasopressors at therapeutic doses (defined as >0.07 μg/kg/min norepinephrine equivalent [Appendix 2]) for at least 2 hours to maintain or attempt to maintain mean arterial pressure ≥65 mm Hg after adequate fluid resuscitation
- Onset of severity criteria <48 hours from diagnosis of CABP or upon discussion with medical monitor
- Requires critical care for management of SCABP
- Written informed consent obtained from subject or legally acceptable representative, as per the local guidelines, before any study-specific assessment is performed; assessments performed as standard of care may be accepted for study purposes
Exclusion Criteria
- Subjects with ventilator-associated pneumonia, aspiration pneumonia, hospital-acquired pneumonia, healthcare-associated pneumonia (HCAP), suspected or confirmed fungal pneumonia, or viral pneumonia (viral coinfection may be exempted subject to medical monitor discussion) (HCAP definition: hospitalization for 2 days or more within the preceding 90 days, residence in a nursing home or extended care facility, the use of home infusion therapy [including antibiotics], receipt of chronic dialysis within 30 days, home wound care and a history of infection with a multidrug-resistant pathogen in a family member)
- More than 12 hours from the diagnosis of SCABP
- SOFA score >12 points and cumulative points from central nervous system + liver function+coagulation ≥4 points at diagnosis of SCABP
- Subject received IV antibiotics for CABP/SCABP for >48 hours at the time of randomization if sensitivity supports appropriate empiric therapy chosen and administered
- Severe renal impairment as determined by estimated serum creatinine clearance of <30 mL/min according to the Cockcroft-Gault equation renal replacement therapy (eg, hemofiltration, hemodialysis, cytokine filters, etc.), or extracorporeal membrane oxygenation (ECMO) at the time of screening or the first IMP infusion
- Known hypersensitivity to egg, egg components, or to liposomal formulations
- End-stage neuromuscular disorders, tracheostomy, known bronchial obstruction (except for chronic obstructive pulmonary disease, asthma, emphysema, and non-cystic fibrosis bronchiectasis), post-obstructive aspiration pneumonia, cystic fibrosis, known or suspected Pneumocystis jirovecii or tuberculosis pneumonia, post organ transplant, or primary or metastatic malignancy in the lungs
- Current or recent participation in an investigational study (within 30 days of screening, or 5 half-lives of the investigational compound, whichever is longer)
- Known liver dysfunction, chronic liver disease with Child Pugh C or esophageal varices
- Moribund clinical conditions at the time of screening or time of the first IMP infusion
- Refractory septic shock at the time of the randomization, as defined by the inability to maintain mean arterial pressure ≥65 mm Hg despite IV fluids and use of any of the following: • Any vasopressor at >0.4 μg/kg/min norepinephrine equivalent (Appendix 2) (Jentzer 2018) or • 2 vasopressors at >0.1 μg/kg/min norepinephrine equivalent (Appendix 2) or • >2 vasopressors at any dose
- Subject has any medical disease (acute, subacute, intermittent, or chronic) or condition (eg, severely immune compromised) that, in the opinion of the investigator, compromises the subject’s safety or compromises the interpretation of the results
- Nursing and pregnant women (defined as the state after conception until the termination of gestation, screened in all women of childbearing potential with a urine dipstick test and, if positive, confirmed by a human chorionic gonadotropin [hCG] blood test)
- Women of childbearing potential and non-surgically sterile male subjects who are sexually active and not willing to use an effective contraception from the time of consent until 30 days after the last dose of IMP unless local regulations require otherwise. Postmenopausal women are allowed to participate
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 10 Jul 2023 | 5 |
 Czechia | Not Yet Recruiting | 10 Jul 2023 | 5 |
 France | Not Yet Recruiting | 10 Jul 2023 | 10 |
 Greece | Not Yet Recruiting | 10 Jul 2023 | 13 |
 Hungary | Not Yet Recruiting | 10 Jul 2023 | 8 |
 Latvia | Not Yet Recruiting | 10 Jul 2023 | 2 |
 Romania | Not Yet Recruiting | 10 Jul 2023 | 25 |
 Slovakia | Not Yet Recruiting | 10 Jul 2023 | 5 |
 Spain | Not Yet Recruiting | 10 Jul 2023 | 8 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Natriumchloride 0,9%, oplossing voor infusie | Placebo | OPLOSSING VOOR INFUSIE | INTRAVENOUS INFUSION | 250 | 2 | PRD2128240 |
CAL02 | Test | SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 1920 | 2 | PRD9987424 |