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

Phase 2

Recruiting

• Conditions: Pneumonia, Bacterial
• Interventions: Drug: Placebo; Drug: 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.

Study Timeline

• Study First Submitted: 2023-02-14
• Study First Submitted QC: 2023-03-07
• Study First Posted: 2023-03-20
• Study Start: 2023-07-22
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-11
• Primary Completion: 2026-02-10
• Study Completion: 2026-09-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 276

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 & 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 (94)

Hospital Central; 🇦🇷 Mendoza, Argentina

Clinique Saint Pierre; 🇧🇪 Ottignies, Belgium

Clinica San Pablo-Sede Surco; 🇵🇪 Lima, Peru

Hospital Nacional Edgardo Rebagliati; 🇵🇪 Lima, Peru

Hospital de la Amistad; 🇵🇪 Piura, Peru

TASK Eden; 🇿🇦 George, South Africa

Univerzitna nemocnica; 🇸🇰 Martin, Slovakia

Chu-Ucl-Namur; 🇧🇪 Yvoir, Belgium

UCSF Hospital; 🇺🇸 Fresno, California, United States

UF Health Shands Hospital; 🇺🇸 Gainesville, Florida, United States

LTD Tbilisi Central Hospital; 🇬🇪 Tbilisi, Georgia

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 Zonal General de Agudos; 🇦🇷 Moreno, Argentina

Clinique Universitaire Saint Luc; 🇧🇪 Bruxelles, Belgium

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

Foothills Hospital Medical Centre; 🇨🇦 Calgary, Alberta, Canada

Peter Lougheed Centre; 🇨🇦 Calgary, Alberta, Canada

Rockyview General Hospital; 🇨🇦 Calgary, Alberta, Canada

South Health Campus Hospital; 🇨🇦 Calgary, Alberta, Canada

Saint Paul's Hospital; 🇨🇦 Vancouver, Canada

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

Hopital Raymond Poincare; 🇫🇷 Garches, 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 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

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

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

Hospital Clínico Universitario de Valladolid; 🇪🇸 Valladolid, Spain