Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19.

COVID-19 Clinical Trial

— CALAVI  

Official title:

A Phase 2, Open Label, Randomized Study of the Efficacy and Safety of Acalabrutinib With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04346199
• Other study ID #: D822FC00001
• Status: Completed
• Phase: Phase 2
• Start date: June 12, 2020
• Est. completion date: November 17, 2020

Study information

• Verified date: September 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CALAVI will investigate the safety, efficacy and pharmacokinetics of acalabrutinib together with Best Supportive Care in the treatment of COVID-19.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: November 17, 2020
• Est. primary completion date: November 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent or have a legal representative provide consent and authorization to use protected health information (in accordance with national and local patient privacy regulations)

2. Men and women =18 years of age at the time of signing the informed consent form

3. Confirmed infection with SARS-CoV-2 confirmed per World Health Organization (WHO) criteria (including positive RT-PCR nucleic acid test of any specimen [eg, respiratory, blood, urine, stool, or other bodily fluid]) within 4 days of randomization

4. COVID-19 pneumonia (documented radiographically) requiring hospitalization and oxygen saturation <94% on room air or requires supplemental oxygen

5. Able to swallow pills

6. Willing to follow contraception guidelines

Exclusion Criteria:

1. Respiratory failure at time of screening due to COVID-19

2. Known medical resuscitation within 14 days of randomization

3. Pregnant or breast feeding

4. Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARS-CoV-2)

5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin = 3x upper limit of normal (ULN) and/or severe hepatic impairment detected within 24 hours at screening (per local lab)

6. Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or congestive heart failure (NYHA Grade 3 or 4). Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll

7. Treatment with a strong cytochrome P450 (CYP)3A inhibitor (within 14 days before first dose of study drug) or inducer (within 7 days before first dose of study drug).

8. Requires treatment with proton-pump inhibitors (PPIs; eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving PPIs who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study

9. Received oral antirejection or immunomodulatory drugs (eg, anticytokines, Btk inhibitors, JAK inhibitors, PI3K inhibitors) within 30 days before randomization on study

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Acalabrutinib
Acalabrutinib- administered orally

Locations

Country	Name	City	State
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Monte Grande
Argentina	Research Site	Ramos Mejía
Brazil	Research Site	Botucatu
Brazil	Research Site	Brasillia
Brazil	Research Site	Florianópolis
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Bernardo do Campo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Chile	Research Site	Curico
Chile	Research Site	Santiago
Chile	Research Site	Talca
France	Research Site	Villejuif Cedex
Germany	Research Site	Frankfurt
Germany	Research Site	Gauting
Germany	Research Site	Köln
India	Research Site	Bangalore
India	Research Site	New Delhi
Italy	Research Site	Milano
Italy	Research Site	Roma
Japan	Research Site	Shinjuku-ku
Mexico	Research Site	D.F
Mexico	Research Site	México
Mexico	Research Site	Monterrey
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Murmansk
South Africa	Research Site	Cape Town
South Africa	Research Site	George
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Pretoria
Turkey	Research Site	Ankara
Turkey	Research Site	Bakirkoy
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Umraniye

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Acerta Pharma BV

Countries where clinical trial is conducted

Argentina,  Brazil,  Chile,  France,  Germany,  India,  Italy,  Japan,  Mexico,  Peru,  Poland,  Russian Federation,  South Africa,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Alive and Free of Respiratory Failure at Day 14	Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of delivered oxygen =0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation	At Day 14
Secondary	Number of Participants With Adverse Events and Serious Adverse Events		Screening to 28 (+3) days after last dose of acalabrutinib (for acalabrutinib + BSC participants) or to 38 (+3) days after randomization (for BSC alone participants)
Secondary	Percentage of Participants Alive and Free of Respiratory Failure at Day 28	Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) Oxygen delivered by highflow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of delivered oxygen =0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation	At Day 28
Secondary	Percent Change From Baseline in C-reactive Protein.	Baseline is defined as the result obtained on the date of randomization. If no result was obtained on the date of randomization, the last result prior to the date of randomization is used.; Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.; The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.	Days 3, 5, 7, 10, 14, 28
Secondary	Percent Change From Baseline in Ferritin	Baseline is defined as the result obtained on the date of randomization. If no result was obtained on the date of randomization, the last result prior to the date of randomization is used.; Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.; The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.	Days 3, 5, 7, 10, 14, 28
Secondary	Percent Change From Baseline in Absolute Lymphocyte Count	Baseline is defined as the result obtained on the date of randomization. If no result was obtained on the date of randomization, the last result prior to the date of randomization is used.; Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.; The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.	Days 3, 5, 7, 10, 14, 28
Secondary	Overall Survival	Median overall survival, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.	From randomization until 90 days after randomization. Safety Issue:
Secondary	Percentage of Participants Alive and Discharged From ICU		At Day 14 and at Day 28
Secondary	Time From Randomization to First Occurrence of Respiratory Failure or Death on Study Due to Any Cause	Median time to first occurrence of respiratory failure or death, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.	From randomization to 28 days after randomization.
Secondary	Number of Days Alive and Free of Respiratory Failure	Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) Oxygen delivered by highflow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of delivered oxygen =0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation	From randomization to 28 days after randomization.
Secondary	Number of Days With Respiratory Failure	Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of delivered oxygen =0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation For participants who die (due to any cause) prior to Day 28, days from death to Day 28 are counted as days with respiratory failure. For participants in hospital and experiencing respiratory failure at the time they withdraw from the study, days from last known status to Day 28 are counted as days with respiratory failure.	From randomization to 28 days after randomization.
Secondary	Number of Days Hospitalized	For this summary, the hospitalization must be considered clinically indicated to count as a day hospitalized.; For participants who die (due to any cause) prior to Day 28, days from death to Day 28 are counted as days hospitalized.; For participants in hospital at the time they withdraw from the study, days from last known status to Day 28 are counted as days hospitalized.	From randomization to 28 days after randomization.
Secondary	Number of Days in ICU	For this summary, the ICU stay must be considered clinically indicated to count as a day in ICU.; For participants who die (due to any cause) prior to Day 90, days from death to Day 90 are counted as days in ICU.	From randomization to 90 days after randomization.
Secondary	Number of Days Alive Outside of Hospital		From randomization to 28 days after randomization.
Secondary	Number of Days Alive Outside of Hospital		From randomization to 90 days after randomization.
Secondary	Percent Change From Baseline in Oxygenation Index	Baseline is defined as the result obtained on the date of randomization.; Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value.; The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.	Days 3, 5, 7, 10, 14, 28
Secondary	Time From Randomization to Clinical Improvement of at Least 2 Points on a 9-point Category Ordinal Scale	9-point category ordinal scale: 0. * Uninfected, no clinical or virological evidence of infection; Ambulatory, no limitation of activities; Ambulatory, limitation of activities; Hospitalized - mild disease, no oxygen therapy; Hospitalized - mild disease, oxygen by mask or nasal prongs; Hospitalized - severe disease, non-invasive ventilation or high flow oxygen; Hospitalised - severe disease, intubation and mechanical ventilation; Hospitalized - severe disease, ventilation and additional organ support, such as pressors, renal replacement therapy, extracorporeal membrane oxygenation; Death; Median time to first occurrence of respiratory failure or death, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.	From randomization to 28 days after randomization.
Secondary	Pharmacokinetics of Acalabrutinib	Summary of plasma concentrations (ng/mL) of acalabrutinib	Day 3 and Day 7
Secondary	Pharmacokinetics of ACP-5862	Summary of plasma concentrations (ng/mL) of ACP-5862	Day 3 and Day 7

External Links

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