Clinical trial NCT04380688: 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: 2020-05-08
Enrollment: 62
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 US 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 criteria (including positive RT-PCR nucleic acid test)
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 the time of screening due to COVID-19 pneumonia that impedes the ability to swallow pills, or in the opinion of the treating physician, the subject is likely to require mechanical ventilation within the immediate 24 hours and therefore unable to swallow pills.
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), and/or aspartate aminotransferase (AST) and/or bilirubin ≥ 3x upper limit of normal (ULN) and/or severe hepatic impairment detected during the screening period (per local lab) Exception: AST and/or ALT ≤5 × ULN if considered due to underlying COVID-19 disease, but cannot be associated with concurrent elevated bilirubin (≤2 × ULN).
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 7 days before first dose of study drug) or inducer (within 14 days before first dose of study drug).

Primary 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
Secondary outcomes:
measure: Percentage of Participants Alive and Free of Respiratory Failure at Day 14
timeFrame: At Day 14
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.
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: Anniston
country: United States
facility: Research Site
state: Alabama
city: Mobile
country: United States
facility: Research Site
state: Alabama
city: Escondido
country: United States
facility: Research Site
state: California
city: Fullerton
country: United States
facility: Research Site
state: California
city: Glendale
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Loxahatchee Groves
country: United States
facility: Research Site
state: Florida
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Annapolis
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Silver Spring
country: United States
facility: Research Site
state: Maryland
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Albany
country: United States
facility: Research Site
state: New York
city: Bronx
country: United States
facility: Research Site
state: New York
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Tyler
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Renton
country: United States
facility: Research Site
state: Washington
Study officials:
References: