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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04346199
Recruitment Status : Completed
First Posted : April 15, 2020
Last Update Posted : February 2, 2021
Sponsor:
Collaborator:
Acerta Pharma BV
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE April 9, 2020
First Posted Date  ICMJE April 15, 2020
Last Update Posted Date February 2, 2021
Actual Study Start Date  ICMJE June 12, 2020
Actual Primary Completion Date November 17, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19.
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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  ICMJE COVID-19
Intervention  ICMJE Drug: Acalabrutinib
Acalabrutinib- administered orally
Study Arms  ICMJE
  • Experimental: Arm 1
    Acalabrutinib+ Best Supportive Care
    Intervention: Drug: Acalabrutinib
  • No Intervention: Arm 2
    Best Supportive Care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 1, 2021)
177
Original Estimated Enrollment  ICMJE
 (submitted: April 14, 2020)
428
Actual Study Completion Date  ICMJE November 17, 2020
Actual Primary Completion Date November 17, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Chile,   France,   Germany,   India,   Italy,   Japan,   Mexico,   Peru,   Russian Federation,   South Africa,   Turkey
Removed Location Countries Spain
 
Administrative Information
NCT Number  ICMJE NCT04346199
Other Study ID Numbers  ICMJE 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  ICMJE
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  ICMJE AstraZeneca
Collaborators  ICMJE Acerta Pharma BV
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP