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

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

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

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Acalabrutinib

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Ciudad de Buenos Aires, Argentina, C1180AAX
    • Research Site
  • Ciudad de Buenos Aires, Argentina, 1221
    • Research Site
  • Monte Grande, Argentina, B1842
    • Research Site
  • Ramos Mejía, Argentina, B1704
    • Research Site
• Brazil
  • Botucatu, Brazil, 18618-687
    • Research Site
  • Brasillia, Brazil, 72145-450
    • Research Site
  • Florianópolis, Brazil, 88036-800
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Porto Alegre, Brazil, 90035-903
    • Research Site
  • Ribeirão Preto, Brazil, 14051-140
    • Research Site
  • Salvador, Brazil, 40110-060
    • Research Site
  • Sao Bernardo do Campo, Brazil, 09715090
    • Research Site
  • Sao Paulo, Brazil, 01327-001
    • Research Site
  • Sao Paulo, Brazil, 04004-030
    • Research Site
  • São Paulo, Brazil, 01308-050
    • Research Site
• Chile
  • Curico, Chile, 3341643
    • Research Site
  • Santiago, Chile, 7500692
    • Research Site
  • Talca, Chile, 3460001
    • Research Site
• France
  • Villejuif Cedex, France, 94805
    • Research Site
• Germany
  • Frankfurt, Germany, 60590
    • Research Site
  • Gauting, Germany, 82131
    • Research Site
  • Köln, Germany, 50937
    • Research Site
• India
  • Bangalore, India, 560002
    • Research Site
  • New Delhi, India, 110017
    • Research Site
• Italy
  • Milano, Italy, 20132
    • Research Site
  • Roma, Italy, 00168
    • Research Site
• Japan
  • Shinjuku-ku, Japan, 162-8655
    • Research Site
• Mexico
  • D.F, Mexico, 14050
    • Research Site
  • Monterrey, Mexico, 64461
    • Research Site
  • México, Mexico, 03103
    • Research Site
• Peru
  • Lima, Peru, LIMA 1
    • Research Site
  • Lima, Peru, LIMA 11
    • Research Site
  • Lima, Peru, 15324
    • Research Site
• Poland
  • Warszawa, Poland, 04-141
    • Research Site
  • Warszawa, Poland, 02-507
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 119992
    • Research Site
  • Moscow, Russian Federation, 143442
    • Research Site
  • Moscow, Russian Federation, 123182
    • Research Site
  • Moscow, Russian Federation, 111539
    • Research Site
  • Murmansk, Russian Federation, 183047
    • Research Site
• South Africa
  • Cape Town, South Africa, 7500
    • Research Site
  • George, South Africa, 6529
    • Research Site
  • Johannesburg, South Africa, 2193
    • Research Site
  • Johannesburg, South Africa, 1827
    • Research Site
  • Pretoria, South Africa, 0157
    • Research Site
• Turkey
  • Ankara, Turkey, 06800
    • Research Site
  • Bakirkoy, Turkey, 34147
    • Research Site
  • Istanbul, Turkey
    • Research Site
  • Istanbul, Turkey, 34214
    • Research Site
  • Umraniye, Turkey, 34760
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Acalabrutinib+ Best Supportive Care	Drug: Acalabrutinib; Acalabrutinib- administered orally
No Intervention: Arm 2; Best Supportive Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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
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
Percentage of Participants Alive and Discharged From ICU		At Day 14 and at Day 28
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.
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.
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.
Number of Days Alive Outside of Hospital		From randomization to 28 days after randomization.
Number of Days Alive Outside of Hospital		From randomization to 90 days after randomization.
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
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.
Pharmacokinetics of Acalabrutinib	Summary of plasma concentrations (ng/mL) of acalabrutinib	Day 3 and Day 7
Pharmacokinetics of ACP-5862	Summary of plasma concentrations (ng/mL) of ACP-5862	Day 3 and Day 7
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
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:
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.
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.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Acerta Pharma BV

Publications and helpful links

Helpful Links

• Redacted CSP
• Redacted CSR Synopsis
• Redacted SAP

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2020
• Primary Completion (Actual): November 17, 2020
• Study Completion (Actual): November 17, 2020

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Actual): September 17, 2021
• Last Update Submitted That Met QC Criteria: September 15, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Acalabrutinib; Btk inhibitor; 2019 novel coronavirus disease
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Antineoplastic Agents; Acalabrutinib
• Other Study ID Numbers: D822FC00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No