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

Pneumonia, Bacterial Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05776004
• Other study ID #: EGL-6535-C-2202
• Status: Recruiting
• Phase: Phase 2
• Start date: July 22, 2023
• Est. completion date: October 2024

Study information

• Verified date: June 2024
• Source: Eagle Pharmaceuticals, Inc.
• Contact: Valentin R Curt, MD
• Phone: 1-888-729-7817
• Email: Eagle2202study[@]inclin.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 276
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Bacterial

Intervention

Drug:
• CAL02
CAL02 consists of a mixture of 2 liposomes and is a non-biological bacterial virulence neutralizer.
• Placebo
Physiological 0.9% sodium chloride solution for iv administration

Locations

Country	Name	City	State
Argentina	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
Brazil	Unidade de Pesquisa Clinica da Faculdade de Medicina de Botucatu	Botucatu
Brazil	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	Hospital do Servidor Publico Estadual	São Paulo
Chile	Pontificia Universidad Catolica de Chile	Santiago
Colombia	Centro de Investigacion Clinica de la Costa SAS	Barranquilla
Colombia	Fundacion Cardioinfantil - Instituto de Cardiologia	Bogotá
Colombia	Fundacion Cardiovascular de Colombia	Piedecuesta
Czechia	Všeobecná fakultní nemocnice - Klinika anesteziologie, resuscitace a intenzivní medicíny (KARIM)	Praha
Czechia	Krajska Zdravotni, a.s.	Teplice
Czechia	Krajska Zdravotni, a.s.	Ústí Nad Labem
Czechia	Oblastní nemocnice Kolín, a.s., nemocnice Stredoceského kraje	Zizkova
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	CHD Vendee	La Roche-sur-Yon	Vendee
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
Georgia	LTD Batumi Medical Center	Batumi
Georgia	JSC Rustavi Central Hospital	Rust'avi
Georgia	LLC Aleksandre Aladashvili Clinic	Tbilisi
Georgia	LTD N5 Clinical Hospital	Tbilisi
Georgia	LTD Simon Khechinashvili University Hospital	Tbilisi
Georgia	LTD Tbilisi Central Hospital	Tbilisi
Georgia	The First Medical Center LTD	Tbilisi
Greece	University General Hospital Attikon	Athens
Greece	University General Hospital	Heraklion
Hungary	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
Latvia	Liepajas Regional Hospital	Liepaja
Latvia	Pauls Stradins Clinical University Hospital	Riga
Latvia	Vidzemes Hospital	Valmiera
Peru	Clinica Ricardo Palma	Lima
Peru	Clinica San Pablo-Sede Surco	Lima
Peru	Hospital de la Amistad	Piura
Romania	Elias University Emergency Hospital	Bucharest
Romania	Fundeni Clinical Institute	Bucharest
Romania	Bihor County Emergency Clinical Hospital	Oradea
Romania	Pius Brinzeu County Emergency Clinical Hospital	Timisoara	Judet Timis
Serbia	University Clinical Centre of Serbia	Belgrad
Serbia	University Clinical Centre	Kragujevac
Serbia	University Clinical Centre	Niš
Serbia	Institute for Pulmonary Diseases	Sremska Kamenica
South Africa	Tygerberg Hospital	Cape Town
South Africa	TASK Eden	George
South Africa	Helen Joseph Academic Hospital	Johannesburg	Gauteng
South Africa	Dr JM Engelbrecht Trial Site	Somerset West
South Africa	FCRN Clinical Trial Centre	Vereeniging	Gauteng
Spain	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
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Cleveland Clinic Fairview Hospital	Cleveland	Ohio
United States	UCSF Hospital	Fresno	California
United States	UF Health Shands Hospital	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Wake Forest Baptist Health Hospital	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eagle Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Chile,  Colombia,  Czechia,  France,  Georgia,  Greece,  Hungary,  Latvia,  Peru,  Romania,  Serbia,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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