NCT04346199: CALAVI

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

Completed Phase 2 Results posted Last updated 17 September 2021

What this trial tests

Phase 2 trial testing Acalabrutinib in COVID-19 in 177 participants. Completed in 17 November 2020.

Timeline

12 June 2020

Primary endpoint
17 November 2020

17 November 2020

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	177
Start date	12 June 2020
Primary completion	17 November 2020
Estimated completion	17 November 2020
Sites	50 locations across France, Italy, Japan, Russia, South Africa, Peru, Chile, Germany

Drugs / interventions tested

• Acalabrutinib (ACALABRUTINIB) — full drug profile →

Conditions studied

• COVID-19 — all drugs for COVID-19 →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Alive and Free of Respiratory Failure at Day 14 Primary · 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

Group	Value	95% CI
Acalabrutinib + BSC	83.1	74.8 – 91.5
BSC Alone	90.9	84.3 – 97.5

Number of Participants With Adverse Events and Serious Adverse Events Secondary · 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)

Any Adverse Event

Group	Value	95% CI
Acalabrutinib + BSC	43
BSC Alone	37

Any Serious Adverse Event

Group	Value	95% CI
Acalabrutinib + BSC	7
BSC Alone	2

Percentage of Participants Alive and Free of Respiratory Failure at Day 28 Secondary · 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

Group	Value	95% CI
Acalabrutinib + BSC	84.3	76.1 – 92.4
BSC Alone	88.6	81.4 – 95.8

Percent Change From Baseline in C-reactive Protein. Secondary · 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.

Day 3

Group	Value	95% CI
Acalabrutinib + BSC	-15.06	± 95.82
BSC Alone	-15.25	± 91.61

Day 5

Group	Value	95% CI
Acalabrutinib + BSC	-12.48	± 113.38
BSC Alone	-41.07	± 92.59

Day 7

Group	Value	95% CI
Acalabrutinib + BSC	-45.71	± 106.84
BSC Alone	-23.41	± 223.06

Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)

Group	Value	95% CI
Acalabrutinib + BSC	-16.84	± 194.71
BSC Alone	-29.32	± 166.35

Day 10

Group	Value	95% CI
Acalabrutinib + BSC	-35.53	± 126.84
BSC Alone	-23.41	± 203.02

Day 14

Group	Value	95% CI
Acalabrutinib + BSC	-12.49	± 187.37
BSC Alone	-17.26	± 256.87

Day 28

Group	Value	95% CI
Acalabrutinib + BSC	-30.28	± 192.90
BSC Alone	-63.74	± 75.28

Percent Change From Baseline in Ferritin Secondary · 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.

Day 3

Group	Value	95% CI
Acalabrutinib + BSC	9.84	± 92.66
BSC Alone	6.49	± 40.23

Day 5

Group	Value	95% CI
Acalabrutinib + BSC	12.92	± 105.09
BSC Alone	-12.76	± 43.18

Day 7

Group	Value	95% CI
Acalabrutinib + BSC	-8.93	± 53.52
BSC Alone	-8.79	± 36.40

Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)

Group	Value	95% CI
Acalabrutinib + BSC	-9.09	± 58.85
BSC Alone	1.35	± 125.95

Day 10

Group	Value	95% CI
Acalabrutinib + BSC	-5.99	± 73.71
BSC Alone	6.84	± 178.23

Day 14

Group	Value	95% CI
Acalabrutinib + BSC	-18.81	± 67.85
BSC Alone	-26.80	± 46.10

Day 28

Group	Value	95% CI
Acalabrutinib + BSC	-66.82	± 18.24
BSC Alone	-66.05	± 21.67

Percent Change From Baseline in Absolute Lymphocyte Count Secondary · 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.

Day 3

Group	Value	95% CI
Acalabrutinib + BSC	31.74	± 59.32
BSC Alone	36.82	± 79.91

Day 5

Group	Value	95% CI
Acalabrutinib + BSC	55.79	± 101.57
BSC Alone	87.25	± 140.37

Day 7

Group	Value	95% CI
Acalabrutinib + BSC	51.72	± 91.82
BSC Alone	79.33	± 119.73

Day 10/ Discharge (last post-baseline assessment if discharged from hospital prior to Day 10)

Group	Value	95% CI
Acalabrutinib + BSC	78.34	± 95.88
BSC Alone	99.65	± 149.02

Day 10

Group	Value	95% CI
Acalabrutinib + BSC	98.55	± 113.66
BSC Alone	83.08	± 105.56

Day 14

Group	Value	95% CI
Acalabrutinib + BSC	74.65	± 124.47
BSC Alone	91.58	± 123.63

Day 28

Group	Value	95% CI
Acalabrutinib + BSC	89.35	± 100.24
BSC Alone	96.62	± 97.30

Overall Survival Secondary · 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.

Group	Value	95% CI
Acalabrutinib + BSC	NA	NA – NA
BSC Alone	NA	NA – NA

Percentage of Participants Alive and Discharged From ICU Secondary · At Day 14 and at Day 28

At Day 14

Group	Value	95% CI
Acalabrutinib + BSC	78.7
BSC Alone	89.8

At Day 28

Group	Value	95% CI
Acalabrutinib + BSC	83.1
BSC Alone	87.5

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

Group	Value	95% CI
Acalabrutinib + BSC	NA	NA – NA
BSC Alone	NA	NA – NA

Number of Days Alive and Free of Respiratory Failure Secondary · 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

Group	Value	95% CI
Acalabrutinib + BSC	24.8	± 8.0
BSC Alone	25.3	± 7.1

Number of Days With Respiratory Failure Secondary · 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 particip

Group	Value	95% CI
Acalabrutinib + BSC	3.2	± 8.0
BSC Alone	2.7	± 7.1

Number of Days Hospitalized Secondary · 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.

Group	Value	95% CI
Acalabrutinib + BSC	12.2	± 8.6
BSC Alone	10.4	± 7.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Screening to 28 (+3) days after last dose of acalabrutinib (for acalabrutinib + BSC treated participants) or to 38 (+3) days after randomization (for BSC alone treated participants). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Acalabrutinib + BSC

Serious: 7/86 (8%)

Deaths: 7/86

BSC Alone

Serious: 2/91 (2%)

Deaths: 10/91

Serious adverse events (10 terms)

Reaction	System	Acalabrutinib + BSC	BSC Alone
Pneumonia	Infections and infestations	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Bacterial sepsis	Infections and infestations	—	—
Mucosal infection	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—
Ischaemic stroke	Nervous system disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Hypotension	Vascular disorders	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Acalabrutinib + BSC	BSC Alone
Headache	Nervous system disorders	—	—

Most-reported serious reactions: Pneumonia, Respiratory failure, Bacterial sepsis, Mucosal infection, Septic shock, Ischaemic stroke, Acute kidney injury, Chronic obstructive pulmonary disease.

Data from ClinicalTrials.gov NCT04346199 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. COVID-19 and Cancer: Current Challenges and Perspectives.
   Bakouny Z, Hawley JE, Choueiri TK, Peters S, et al · · 2020 · cited 201× · PMID 33049215 · DOI 10.1016/j.ccell.2020.09.018
2. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection.
   Copaescu A, Smibert O, Gibson A, Phillips EJ, et al · · 2020 · cited 196× · PMID 32896310 · DOI 10.1016/j.jaci.2020.07.001
3. Small Molecule NF-κB Pathway Inhibitors in Clinic.
   Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
4. The interplay between inflammatory pathways and COVID-19: A critical review on pathogenesis and therapeutic options.
   Choudhary S, Sharma K, Silakari O. · · 2021 · cited 116× · PMID 33278517 · DOI 10.1016/j.micpath.2020.104673
5. Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines.
   Pleyer C, Ali MA, Cohen JI, Tian X, et al · · 2021 · cited 109× · PMID 33259596 · DOI 10.1182/blood.2020008758
6. COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies.
   Goldman JD, Robinson PC, Uldrick TS, Ljungman P. · · 2021 · cited 88× · PMID 34117116 · DOI 10.1136/jitc-2021-002630
7. Potential therapeutic targets for combating SARS-CoV-2: Drug repurposing, clinical trials and recent advancements.
   Pandey A, Nikam AN, Shreya AB, Mutalik SP, et al · · 2020 · cited 80× · PMID 32497632 · DOI 10.1016/j.lfs.2020.117883
8. Protective role of Bruton tyrosine kinase inhibitors in patients with chronic lymphocytic leukaemia and COVID-19.
   Thibaud S, Tremblay D, Bhalla S, Zimmerman B, et al · · 2020 · cited 72× · PMID 32433778 · DOI 10.1111/bjh.16863