Blinded Efficacy and Safety Study of CAL02 IV Plus SOC in Subjects With Severe Community-Acquired Bacterial Pneumonia
- Conditions
- Pneumonia, Bacterial
- Interventions
- Drug: PlaceboDrug: CAL02
- Registration Number
- NCT05776004
- Lead Sponsor
- Eagle Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 276
- 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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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. CAL02 with Standard of Care CAL02 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.
- Primary Outcome Measures
Name Time Method Efficacy- clinical recovery 28 days 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.
Incidence of Treatment-Emergent Adverse Events 28 days 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.
- Secondary Outcome Measures
Name Time Method Critical Care Management 28 days 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.
Hospital Stay 28 days 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.
Organ Failure Assessment Scores 7 days 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.
Early Clinical Recovery 5 days 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.
Trial Locations
- Locations (83)
UCSF Hospital
🇺🇸Fresno, California, United States
UF Health Shands Hospital
🇺🇸Gainesville, Florida, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Wake Forest Baptist Health Hospital
🇺🇸Winston-Salem, North Carolina, United States
Cleveland Clinic Fairview Hospital
🇺🇸Cleveland, Ohio, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Hospital Interzonal General de Agudo Dr Jose Pena
🇦🇷Bahía Blanca, Buenos Aires, Argentina
Hospital de Alta Complejidad Cuenca Alta SAMIC
🇦🇷Cañuelas, Buenos Aires, Argentina
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Hospital Misericordia Nuevo Siglo
🇦🇷Córdoba, Argentina
Hospital Central
🇦🇷Mendoza, Argentina
Hospital Zonal General de Agudos
🇦🇷Moreno, Argentina
Santa Casa de Curitiba
🇧🇷Curitiba, Parana, Brazil
Hospital Mae de Deus
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
🇧🇷São José Do Rio Preto, Sao Paulo, Brazil
Unidade de Pesquisa Clinica da Faculdade de Medicina de Botucatu
🇧🇷Botucatu, Brazil
Hospital do Servidor Publico Estadual
🇧🇷São Paulo, Brazil
Pontificia Universidad Catolica de Chile
🇨🇱Santiago, Chile
Centro de Investigacion Clinica de la Costa SAS
🇨🇴Barranquilla, Colombia
Fundacion Cardioinfantil - Instituto de Cardiologia
🇨🇴Bogotá, Colombia
Fundacion Cardiovascular de Colombia
🇨🇴Piedecuesta, Colombia
Všeobecná fakultní nemocnice - Klinika anesteziologie, resuscitace a intenzivní medicíny (KARIM)
🇨🇿Praha, Czechia
Krajska Zdravotni, a.s.
🇨🇿Ústí Nad Labem, Czechia
Oblastní nemocnice Kolín, a.s., nemocnice Středočeského kraje
🇨🇿Zizkova, Czechia
CHD Vendee
🇫🇷La Roche-sur-Yon, Vendee, France
CHU Angers
🇫🇷Angers, France
Centre Hospitalier Victor Dupouy
🇫🇷Argenteuil, France
Hopital Nord Franche Comte
🇫🇷Belfort, France
Hospital Fleyriat
🇫🇷Bourg-en-Bresse, France
Centre Hospitalier de Dieppe
🇫🇷Dieppe, France
Plateforme de Biologie Hospitalo-Universitaire
🇫🇷Dijon, France
Pole Urgences Medecine Aigue CHU de Grenoble-Alpes
🇫🇷Grenoble, France
Hospital Dupuytren
🇫🇷Limoges, France
Centre Hospitalier de Melun-Senart
🇫🇷Melun, France
CHU de Nantes
🇫🇷Nantes, France
Hopitaux Universitaires de Strasbourg - Nouvel Hopital Civil
🇫🇷Strasbourg, France
Centre Hospitalier Bretagne Atlantique
🇫🇷Vannes, France
LTD Batumi Medical Center
🇬🇪Batumi, Georgia
JSC Rustavi Central Hospital
🇬🇪Rust'avi, Georgia
LLC Aleksandre Aladashvili Clinic
🇬🇪Tbilisi, Georgia
LTD Tbilisi Central Hospital
🇬🇪Tbilisi, Georgia
LTD Simon Khechinashvili University Hospital
🇬🇪Tbilisi, Georgia
The First Medical Center LTD
🇬🇪Tbilisi, Georgia
LTD N5 Clinical Hospital
🇬🇪Tbilisi, Georgia
Thoracic General Hospital
🇬🇷Athens, Greece
University General Hospital Attikon
🇬🇷Athens, Greece
University General Hospital
🇬🇷Heraklion, Greece
Bekes Varmegyei Kozponti K6rhaz
🇭🇺Gyula, Hungary
Szaboles-Szatmar-Bereg Varmegyei Oktatokorhaz
🇭🇺Nyiregyhaza, Hungary
Borsod-Abauj-Zemplen Varmegyei Kozponti Korhaz es Egyetemi Oktatov
🇭🇺Szentpeteri Kapu, Hungary
Zala Varmegyei Szent Rafael Korbaz
🇭🇺Zalaegerszeg, Hungary
Liepajas Regional Hospital
🇱🇻Liepāja, Latvia
Pauls Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Vidzemes Hospital
🇱🇻Valmiera, Latvia
Hospital Nacional III
🇵🇪Arequipa, Peru
Clinica Ricardo Palma
🇵🇪Lima, Peru
Clinica San Pablo-Sede Surco
🇵🇪Lima, Peru
Hospital Nacional Edgardo Rebagliati
🇵🇪Lima, Peru
Hospital de la Amistad
🇵🇪Piura, Peru
Pius Brinzeu County Emergency Clinical Hospital
🇷🇴Timişoara, Judet Timis, Romania
Elias University Emergency Hospital
🇷🇴Bucharest, Romania
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
Cluj County Emergency Clinical Hospital
🇷🇴Cluj-Napoca, Romania
Bihor County Emergency Clinical Hospital
🇷🇴Oradea, Romania
University Clinical Centre of Serbia
🇷🇸Belgrad, Serbia
University Clinical Centre
🇷🇸Niš, Serbia
Institute for Pulmonary Diseases
🇷🇸Sremska Kamenica, Serbia
Helen Joseph Academic Hospital
🇿🇦Johannesburg, Gauteng, South Africa
FCRN Clinical Trial Centre
🇿🇦Vereeniging, Gauteng, South Africa
Tygerberg Hospital
🇿🇦Cape Town, South Africa
TASK Eden
🇿🇦George, South Africa
Ryexo Clinical Research
🇿🇦Pretoria, South Africa
Dr JM Engelbrecht Trial Site
🇿🇦Somerset West, South Africa
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Parc Tauli Hospital Universitari
🇪🇸Barcelona, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
C.H.U de Santiago de Compostela
🇪🇸Santiago De Compostela, Spain
Hospital Universitario de Tarragona Joan XXIII
🇪🇸Tarragona, Spain
Hospital Universitari Mutua Terrassa
🇪🇸Terrassa, Spain
Hospital Universitario de Toledo
🇪🇸Toledo, Spain
Hospital Universitario Dr Peset
🇪🇸Valencia, Spain