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

• ClinicalTrials.gov Identifier: NCT04346199
• Recruitment Status: Completed
• First Posted: April 15, 2020
• Last Update Posted: February 2, 2021
• Sponsor: AstraZeneca
• Collaborator: Acerta Pharma BV
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: April 9, 2020
• First Posted Date: April 15, 2020
• Last Update Posted Date: February 2, 2021
• Actual Study Start Date: June 12, 2020
• Actual Primary Completion Date: November 17, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2020)

Subject alive and free of respiratory failure [ Time Frame: Day 14 ]

Respiratory failure, is defined based on resource utilization of any of the following modalities:

1. Endotracheal intubation and mechanical ventilation
2. 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)
3. Noninvasive positive pressure ventilation or continuous positive airway pressure
4. Extracorporeal membrane oxygenation

Original Primary Outcome Measures (submitted: April 14, 2020)

Treatment failure rate [ Time Frame: Approximately 30 days ]

Treatment failure rate, where treatment failure is defined as use of assisted ventilation or death.

Current Secondary Outcome Measures (submitted: May 7, 2020)

• Proportion of subjects alive and free of respiratory failure [ Time Frame: Day 28 ]
• Percent change from baseline in CRP [ Time Frame: Days 3, 5, 7, 10, 14, 28 ]
• Change from baseline in ferritin [ Time Frame: Days 3, 5, 7, 10, 14, 28 ]
• Chnage from baseline in absolute lymphocyte counts [ Time Frame: Days 3, 5, 7, 10, 14, 28 ]
• All cause mortality [ Time Frame: Day 90 ]
• Proportion of subjects alive and discharged from ICU [ Time Frame: Days 14 and 28 ]
• Time from randomization to first occurrence of respiratory failure or death on study due to any cause [ Time Frame: Up to 28 days after randomization ]
• Number of days alive and free of respiratory failure [ Time Frame: To 28 days after randomization ]
• Number of days with respiratory failure [ Time Frame: to 28 days after randomization ]
• Number of days hospitalized [ Time Frame: To 28 days after randomization ]
• Number of days in ICU (length of stay) [ Time Frame: To 90 days after randomization ]
• Number of days alive outside of hospital [ Time Frame: To 28 days after randomization ]
• Number of days alive outside of hospital [ Time Frame: To 90 days after randomization ]
• Relative change from baseline in oxygenation index (PaO2/FiO2) [ Time Frame: To Day 5 ]
• Occurrence of Adverse Events and Serious Adverse Events [ Time Frame: 28 days after last dose ]
  Type, frequency, severity, and relationship to study treatment of any TEAEs or abnormalities of laboratory tests, SAEs, or AEs leading to discontinuation of study treatment.
• Pharmacokinetics of acalabrutinib and its active metabolite ACP- 5862 (Cmax) [ Time Frame: 28 days after last dose ]
  Peak Plasma Concentration (Cmax)
• Pharmacokinetics of acalabrutinib and its active metabolite ACP- 5862 (Tmax) [ Time Frame: 28 days after last dose ]
  Time to Maximum Concentration (Tmax)
• Pharmacokinetics of acalabrutinib and its active metabolite ACP- 5862 (AUC) [ Time Frame: 28 days after last dose ]
  Area under the plasma concentration versus time curve (AUC)

Original Secondary Outcome Measures (submitted: April 14, 2020)

• Number of days alive free of assisted ventilation [ Time Frame: Approximately 30 days ]
• Number of days with assisted ventilator use [ Time Frame: Approximately 30 days ]
• Number of days hospitalized [ Time Frame: Approximately 30 days ]
• Number of days in ICU [ Time Frame: Approximately 30 days ]
• Number of days alive outside of hospital [ Time Frame: Approximately 30 days ]
• Number of days alive outside of hospital [ Time Frame: Approximately 90 days ]
• Occurrence of Adverse Events and Serious Adverse Events [ Time Frame: Approximately 30 days ]
• Pharmacokinetics of acalabrutinib and its active metabolite ACP- 5862 (Cmax) [ Time Frame: Approximately 30 days ]
  Peak Plasma Concentration (Cmax)
• Pharmacokinetics of acalabrutinib and its active metabolite ACP- 5862 (Tmax) [ Time Frame: Approximately 30 days ]
  Time to Maximum Concentration (Tmax)
• Pharmacokinetics of acalabrutinib and its active metabolite ACP- 5862 (AUC) [ Time Frame: Approximately 30 days ]
  Area under the plasma concentration versus time curve (AUC)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Brief Summary: CALAVI will investigate the safety, efficacy and pharmacokinetics of acalabrutinib together with Best Supportive Care in the treatment of COVID-19.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Study will consist of two arms Arm 1 is acalabrutinib + best supportive care or Arm 2 is best supportive care alone

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: COVID-19

Intervention

Drug: Acalabrutinib

Acalabrutinib- administered orally

Study Arms

• Experimental: Arm 1
  Acalabrutinib+ Best Supportive Care
  Intervention: Drug: Acalabrutinib
• No Intervention: Arm 2
  Best Supportive Care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 1, 2021): 177
• Original Estimated Enrollment (submitted: April 14, 2020): 428
• Actual Study Completion Date: November 17, 2020
• Actual Primary Completion Date: November 17, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Chile, France, Germany, India, Italy, Japan, Mexico, Peru, Russian Federation, South Africa, Turkey
• Removed Location Countries: Spain

Administrative Information

• NCT Number: NCT04346199
• Other Study ID Numbers: D822FC00001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• 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.
• 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.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Acerta Pharma BV
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: January 2021