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

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)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Pneumonia, Bacterial
• Intervention / Treatment: Drug: CAL02; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 276
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina
    • Hospital Misericordia Nuevo Siglo
  • Mendoza, Argentina
    • Hospital Central
  • Buenos Aires
    • Bahía Blanca, Buenos Aires, Argentina
      • Hospital Interzonal General de Agudo Dr Jose Pena
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1199ABB
      • Hospital Italiano de Buenos Aires
• Belgium
  • Brussels, Belgium
    • Clinique Universitaire Saint LUC
  • Ottignies, Belgium
    • Clinique Saint Pierre
  • Yvoir, Belgium
    • Chu-Ucl-Namur
• Brazil
  • Botucatu, Brazil
    • Unidade de Pesquisa Clinica da Faculdade de Medicina de Botucatu
  • São Paulo, Brazil
    • Hospital do Servidor Público Estadual
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90880-480
      • Hospital Mae de Deus
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto
• Canada
  • Vancouver, Canada
    • Saint Paul's Hospital
  • Alberta
    • Calgary, Alberta, Canada
      • Rockyview General Hospital
    • Calgary, Alberta, Canada
      • Peter Lougheed Centre
    • Calgary, Alberta, Canada
      • Foothills Hospital Medical Centre
    • Calgary, Alberta, Canada
      • South Health Campus Hospital
• Chile
  • Santiago, Chile
    • Pontificia Universidad Catolica de Chile
• Colombia
  • Barranquilla, Colombia
    • Centro de Investigacion Clinica de la Costa SAS
  • Bogotá, Colombia
    • Fundacion Cardioinfantil - Instituto de Cardiologia
• Czechia
  • Teplice, Czechia
    • Krajska Zdravotni, a.s.
  • Zizkova, Czechia
    • Oblastní nemocnice Kolín, a.s., nemocnice Středočeského kraje
  • Ústí nad Labem, Czechia
    • Krajska Zdravotni, a.s.
• France
  • Angers, France
    • CHU Angers
  • Argenteuil, France
    • Centre Hospitalier Victor Dupouy
  • Belfort, France
    • Hopital Nord Franche Comte
  • Bourg-en-Bresse, France
    • Hospital Fleyriat
  • Dieppe, France
    • Centre Hospitalier de Dieppe
  • Dijon, France
    • Plateforme de Biologie Hospitalo-Universitaire
  • Garches, France
    • Hopital Raymond Poincare
  • Grenoble, France
    • Pole Urgences Medecine Aigue CHU de Grenoble-Alpes
  • Limoges, France
    • Hospital Dupuytren
  • Melun, France
    • Centre Hospitalier de Melun-Senart
  • Nantes, France
    • CHU de Nantes
  • Strasbourg, France
    • Hôpitaux Universitaires de Strasbourg - Nouvel Hôpital Civil
  • Vannes, France
    • Centre Hospitalier Bretagne Atlantique
  • Vendee
    • La Roche-sur-Yon, Vendee, France
      • CHD Vendee
• Georgia
  • Batumi, Georgia, 6400
    • LTD Batumi Medical Center
  • Rustavi, Georgia, 3700
    • JSC Rustavi Central Hospital
  • Tbilisi, Georgia, 0179
    • LTD Simon Khechinashvili University Hospital
  • Tbilisi, Georgia, 0159
    • Ltd Tbilisi Central Hospital
  • Tbilisi, Georgia, 0180
    • The First Medical Center LTD
  • Tbilisi, Georgia, 0102
    • LLC Aleksandre Aladashvili Clinic
  • Tbilisi, Georgia, 0197
    • LTD N5 Clinical Hospital
• Greece
  • Athens, Greece
    • University General Hospital Attikon
  • Athens, Greece
    • Thoracic General Hospital
  • Heraklion, Greece
    • University General Hospital
• Hungary
  • Gyula, Hungary
    • Bekes Varmegyei Kozponti K6rhaz
  • Nyíregyháza, Hungary
    • Szaboles-Szatmar-Bereg Varmegyei Oktatokorhaz
  • Szentpeteri Kapu, Hungary
    • Borsod-Abauj-Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktatov
  • Zalaegerszeg, Hungary
    • Zala Varmegyei Szent Rafael Korbaz
• Latvia
  • Liepāja, Latvia
    • Liepajas Regional Hospital
  • Riga, Latvia
    • Pauls Stradins Clinical University Hospital
  • Valmiera, Latvia
    • Vidzemes Hospital
• Peru
  • Arequipa, Peru
    • Hospital Nacional III
  • Lima, Peru
    • Clinica Ricardo Palma
  • Lima, Peru
    • Clinica San Pablo-Sede Surco
  • Lima, Peru
    • Hospital Nacional Edgardo Rebagliati
  • Piura, Peru
    • Hospital de la Amistad
• Romania
  • Bucharest, Romania
    • Fundeni Clinical Institute
  • Bucharest, Romania
    • Elias University Emergency Hospital
  • Cluj-Napoca, Romania
    • Cluj County Emergency Clinical Hospital
  • Oradea, Romania
    • Bihor County Emergency Clinical Hospital
  • Judet Timis
    • Timișoara, Judet Timis, Romania
      • Pius Brinzeu County Emergency Clinical Hospital
• Serbia
  • Belgrade, Serbia
    • University Clinical Centre of Serbia
  • Kamenitz, Serbia
    • Institute for Pulmonary Diseases
  • Kragujevac, Serbia
    • University Clinical Centre
  • Niš, Serbia
    • University Clinical Centre
• Slovakia
  • Martin, Slovakia
    • Univerzitna nemocnica
• South Africa
  • Cape Town, South Africa
    • Tygerberg hospital
  • Pretoria, South Africa
    • Ryexo Clinical Research
  • Somerset West, South Africa, 7130
    • Dr JM Engelbrecht Trial Site
  • Gauteng
    • Johannesburg, Gauteng, South Africa
      • Helen Joseph Academic Hospital
    • Vereeniging, Gauteng, South Africa, 1935
      • FCRN Clinical Trial Centre
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Parc Tauli Hospital Universitari
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario Infanta Leonor
  • Santiago de Compostela, Spain
    • C.H.U de Santiago de Compostela
  • Tarragona, Spain
    • Hospital Universitario de Tarragona Joan XXIII
  • Terrassa, Spain
    • Hospital Universitari Mutua Terrassa
  • Toledo, Spain
    • Hospital Universitario de Toledo
  • Valencia, Spain
    • Hospital Universitario Dr Peset
  • Valladolid, Spain
    • Hospital Clinico Universitario de Valladolid
• United States
  • California
    • Fresno, California, United States, 93701
      • UCSF Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Health Shands Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Fairview Hospital
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAL02 with Standard of Care; 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; CAL02 consists of a mixture of 2 liposomes and is a non-biological bacterial virulence neutralizer.
Placebo Comparator: Placebo; 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; Physiological 0.9% sodium chloride solution for iv administration

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

Collaborators and Investigators

• Sponsor: Eagle Pharmaceuticals, Inc.
• Investigators: Study Chair: Valentin R Curt, MD, Eagle Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2023
• Primary Completion (Estimated): February 10, 2026
• Study Completion (Estimated): September 7, 2026

Study Registration Dates

• First Submitted: February 14, 2023
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Community-Acquired
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia, Bacterial
• Other Study ID Numbers: EGL-6535-C-2202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No