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Completed

NCT Number: NCT04346199

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

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

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Key information

Conditions

COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year–130 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Ciudad de Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)
  • Men and women ≥18 years of age at the time of signing the informed consent form
  • 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
  • COVID-19 pneumonia (documented radiographically) requiring hospitalization and oxygen saturation <94% on room air or requires supplemental oxygen
  • Able to swallow pills
  • Willing to follow contraception guidelines

Exclusion criteria

  • Respiratory failure at time of screening due to COVID-19
  • Known medical resuscitation within 14 days of randomization
  • Pregnant or breast feeding
  • Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARS-CoV-2)
  • 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)
  • 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
  • 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).
  • 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
  • Received oral antirejection or immunomodulatory drugs (eg, anticytokines, Btk inhibitors, JAK inhibitors, PI3K inhibitors) within 30 days before randomization on study

Treatment and study plan

Acalabrutinib

Drug

Acalabrutinib- administered orally

Primary outcomes

  1. Percentage of Participants Alive and Free of Respiratory Failure at Day 14

    Time frame: 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

Secondary outcomes

  1. Number of Participants With Adverse Events and Serious Adverse Events

    Time frame: 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)

  2. Percentage of Participants Alive and Free of Respiratory Failure at Day 28

    Time frame: 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

  3. Percent Change From Baseline in C-reactive Protein.

    Time frame: Days 3, 5, 7, 10, 14, 28

    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.

  4. Percent Change From Baseline in Ferritin

    Time frame: Days 3, 5, 7, 10, 14, 28

    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.

  5. Percent Change From Baseline in Absolute Lymphocyte Count

    Time frame: Days 3, 5, 7, 10, 14, 28

    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.

  6. Overall Survival

    Time frame: From randomization until 90 days after randomization. Safety Issue:

    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.

  7. Percentage of Participants Alive and Discharged From ICU

    Time frame: At Day 14 and at Day 28

  8. Time From Randomization to First Occurrence of Respiratory Failure or Death on Study Due to Any Cause

    Time frame: From randomization to 28 days after randomization.

    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.

  9. Number of Days Alive and Free of Respiratory Failure

    Time frame: From randomization to 28 days after randomization.

    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

  10. Number of Days With Respiratory Failure

    Time frame: From randomization to 28 days after randomization.

    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.

  11. Number of Days Hospitalized

    Time frame: From randomization to 28 days after randomization.

    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.

  12. Number of Days in ICU

    Time frame: From randomization to 90 days after randomization.

    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.

  13. Number of Days Alive Outside of Hospital

    Time frame: From randomization to 28 days after randomization.

  14. Number of Days Alive Outside of Hospital

    Time frame: From randomization to 90 days after randomization.

  15. Percent Change From Baseline in Oxygenation Index

    Time frame: Days 3, 5, 7, 10, 14, 28

    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.

  16. Time From Randomization to Clinical Improvement of at Least 2 Points on a 9-point Category Ordinal Scale

    Time frame: From randomization to 28 days after randomization.

    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.

  17. Pharmacokinetics of Acalabrutinib

    Time frame: Day 3 and Day 7

    Summary of plasma concentrations (ng/mL) of acalabrutinib

  18. Pharmacokinetics of ACP-5862

    Time frame: Day 3 and Day 7

    Summary of plasma concentrations (ng/mL) of ACP-5862

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Acerta Pharma BV

Registry information

Official study 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

Acronym: CALAVI

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Apr 15, 2020
Registry last updated
Sep 17, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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