Blinded Efficacy and Safety Study of CAL02 IV Plus SOC in Subjects With Severe Community-Acquired Bacterial Pneumonia

Study Overview
=================
Brief Summary
-----------------
This is a placebo-controlled study to evaluate the addition of CAL02 to standard of care in treating hospitalized subjects diagnosed with severe community acquired bacterial pneumonia (SCABP) requiring critical care measures

Detailed Description
-----------------
Subjects diagnosed with SCABP and requiring critical care measures, will receive either 2 intravenous infusions of CAL02 (13.7 to 24 mg/kg bracketed dose by weight), administered 24-26 hours apart or 2 intravenous infusions of placebo. Additionally, all subjects will receive standard of care (SOC) therapy for SCABP, according to scientific guidelines. Critical care measures provide intensive and specialized medical and nursing care, a capacity for continuous monitoring 24 hours/day, and multiple modalities of physiologic organ support to sustain life in seriously/critically ill patients.

Official Title
-----------------
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)

Conditions
-----------------
Pneumonia, Bacterial

Intervention / Treatment
-----------------
* Drug: CAL02
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: male or females older than 18 years old Body Weight 40 - 140 kg; clinical diagnosis of CABP diagnosed less than or equal to 48 hrs after hospital admission; presence of at least one of the protocol defined SCABP severity criteria: at least two clinical symptoms at least 2 vital sign abnormalities at least one finding of other clinical signs/laboratory abnormalities radiographic evidence in support of pneumonia with likely bacterial origin presence of at least one of the following severity criteria based on protocol defined SCABP: respiratory failure requiring invasive mechanical ventilation support respiratory failure requiring non-invasive positive pressure ventilation support respiratory failure requiring high-flow oxygen septic shock requiring treatment with vasopressors at therapeutic doses for at least 2 hours requires critical care for management of SCABP onset of severity criteria less than 48 hours from diagnosis of CABP or upon discussion with medical monitor written informed consent before any study-specific assessment is performed Exclusion Criteria: Subjects in the hospital who meet any of the following criteria at screening and before study drug administration: subjects with ventilator-associated pneumonia, aspiration pneumonia, fungal pneumonia, viral pneumonia (viral coinfection may be exempted subject to discussion with medical monitor); subjects more than 12 hours from the diagnosis of SCABP; SOFA score greater than 12 points subject received IV antibiotics for CABP/SCABP for more than 48 hours at the time of randomization if sensitivity supports appropriate empiric therapy chosen and administered renal replacement therapy known hypersensitivity to liposomal formulations end-stage neuromuscular disorders, tracheostomy, known bronchial obstruction, post-operative 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 study medication infusion refractory septic shock at the time of randomization subject has any medical disease or condition that, in the opinion of the investigator, compromises the subject's safety or compromises the interpretation of results nursing and pregnant women women of childbearing potential and non-surgically sterile males

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Adaptive, randomized, double-blind, placebo-controlled study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAL02 with Standard of Care<br>CAL02 (a mixture of 2 liposomal components, both empty, unilamellar, liposomes) will be administered as 2, IV infusions, 24 - 26 hours apart in addition to Standard of Care therapy for SCABP, according to scientific guidelines. CAL02 infusions will be administered over a 1 -2 hour period. | Drug: CAL02<br>* CAL02 consists of a mixture of 2 liposomes and is a non-biological bacterial virulence neutralizer.<br>|
| Placebo Comparator: Placebo<br>Placebo will be administered as 2, IV infusions, 24 - 26 hours apart in addition to Standard of Care therapy for SCABP, according to scientific guidelines. Placebo will be prepared and administered following the same infusion protocol as CAL02. Placebo infusions will be administered over a 1 to 2 hour period. | Drug: Placebo<br>* Physiological 0.9% sodium chloride solution for iv administration<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy- clinical recovery | To evaluate the effect of CAL02 administration on clinical recovery compared to placebo. The time (days) to clinical recovery will be measured, as defined by the day all disease severity criteria which led to SCABP diagnosis per protocol at randomization and any new severity criteria which occurred after randomization are resolved, and no repeat or additional severity criteria are met within 24 hours after clinical recovery. | 28 days | 
| Incidence of Treatment-Emergent Adverse Events | To evaluate the safety and tolerability of CAL02 versus placebo. The number of participants with treatment-emergent adverse events including IV infusion-related reactions, and the number of participants with study drug dosing interruptions and discontinuations will be measured. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Critical Care Management | To evaluate the effect of CAL02 administration on the duration of critical care management compared to placebo. The time (days) participant remains in hospital critical care from randomization until discharge will be measured. | 28 days | 
| Hospital Stay | To evaluate the effect of CAL02 administration on the duration of overall hospital stay compared to placebo. The time (days) participant remains in hospital from randomization until discharge will be measured. | 28 days | 
| Early Clinical Recovery | To evaluate the effect of CAL02 administration on early clinical recovery (by Day 5) compared to placebo. The number of participants who achieve clinical recovery by Day 5 will be assessed; clinical recovery as defined by the day all disease severity criteria which led to SCABP diagnosis per protocol at randomization and any new severity criteria which occurred after randomization are resolved, and no repeat or additional severity criteria are met within 24 hours after clinical recovery. | 5 days | 
| Organ Failure Assessment Scores | To evaluate the effects of CAL02 administration on Sequential Organ Failure Assessment (SOFA) scores compared to placebo. The minimum total score is 0 and the maximum total score is 24. A higher total SOFA score indicates worse outcome. | 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Community-Acquired