Clinical trial NCT04346199: Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: 2019 novel coronavirus disease
Acalabrutinib
Btk inhibitor
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Acerta Pharma BV
First posted: 2020-04-15
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study will consist of two arms Arm 1 is acalabrutinib + best supportive care or Arm 2 is best supportive care alone
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Alive and Free of Respiratory Failure at Day 14
timeFrame: At Day 14
Secondary outcomes:
measure: Number of Participants With Adverse Events and Serious Adverse Events
timeFrame: 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)
measure: Percentage of Participants Alive and Free of Respiratory Failure at Day 28
timeFrame: At Day 28
measure: Percent Change From Baseline in C-reactive Protein.
timeFrame: Days 3, 5, 7, 10, 14, 28
measure: Percent Change From Baseline in Ferritin
timeFrame: Days 3, 5, 7, 10, 14, 28
measure: Percent Change From Baseline in Absolute Lymphocyte Count
timeFrame: Days 3, 5, 7, 10, 14, 28
measure: Overall Survival
timeFrame: From randomization until 90 days after randomization. Safety Issue:
measure: Percentage of Participants Alive and Discharged From ICU
timeFrame: At Day 14 and at Day 28
measure: Time From Randomization to First Occurrence of Respiratory Failure or Death on Study Due to Any Cause
timeFrame: From randomization to 28 days after randomization.
measure: Number of Days Alive and Free of Respiratory Failure
timeFrame: From randomization to 28 days after randomization.
measure: Number of Days With Respiratory Failure
timeFrame: From randomization to 28 days after randomization.
measure: Number of Days Hospitalized
timeFrame: From randomization to 28 days after randomization.
measure: Number of Days in ICU
timeFrame: From randomization to 90 days after randomization.
measure: Number of Days Alive Outside of Hospital
timeFrame: From randomization to 28 days after randomization.
measure: Number of Days Alive Outside of Hospital
timeFrame: From randomization to 90 days after randomization.
measure: Percent Change From Baseline in Oxygenation Index
timeFrame: Days 3, 5, 7, 10, 14, 28
measure: Time From Randomization to Clinical Improvement of at Least 2 Points on a 9-point Category Ordinal Scale
timeFrame: From randomization to 28 days after randomization.
measure: Pharmacokinetics of Acalabrutinib
timeFrame: Day 3 and Day 7
measure: Pharmacokinetics of ACP-5862
timeFrame: Day 3 and Day 7
Other outcomes:
Locations:
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aires
country: Argentina
facility: Research Site
city: Monte Grande
country: Argentina
facility: Research Site
city: Ramos Mejía
country: Argentina
facility: Research Site
city: Botucatu
country: Brazil
facility: Research Site
city: Brasillia
country: Brazil
facility: Research Site
city: Florianópolis
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: Sao Bernardo do Campo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Curico
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Talca
country: Chile
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: D.F
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Murmansk
country: Russian Federation
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: George
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Bakirkoy
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Umraniye
country: Turkey
facility: Research Site
Study officials:
References: