Acalabrutinib Study With Best Supportive Care in Participants Hospitalized With COVID-19

• ClinicalTrials.gov Identifier: NCT04497948
• Recruitment Status: Terminated
• First Posted: August 4, 2020
• Results First Posted: November 5, 2021
• Last Update Posted: November 17, 2021
• Sponsor: Acerta Pharma BV
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Acerta Pharma BV

Tracking Information

• First Submitted Date: June 16, 2020
• First Posted Date: August 4, 2020
• Results First Submitted Date: October 29, 2021
• Results First Posted Date: November 5, 2021
• Last Update Posted Date: November 17, 2021
• Actual Study Start Date: September 21, 2020
• Actual Primary Completion Date: November 18, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 29, 2021)

• Area Under the Concentration-time Curve From 0 to 12 Hours (AUC12h) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5) [ Time Frame: pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day 5 ]
  To summarize the PK parameter AUC12h of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC + PPI
• Area Under the Concentration-time Curve From 0 to Time to Last Quantifiable Concentration (AUClast) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5) [ Time Frame: pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day5 ]
  To summarize the PK parameter AUClast for Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI
• Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) [ Time Frame: pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1(Day 1), visit 2(Day 2) and visit 3(Day 5) ]
  To summarize the PK parameter Cmax of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI

Original Primary Outcome Measures (submitted: July 31, 2020)

• Acalabrutinib and ACP-5862 plasma PK parameter: AUC12h [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, and 12 hours post-dose ]
  To assess the AUC12h (area under plasma concentration-time curve from time zero to 12 hours) of the acalabrutinib NG suspension when coadministered with the PPI in participants with COVID-19
• Acalabrutinib and ACP-5862 plasma PK parameter: AUClast [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, and 12 hours post-dose ]
  To assess the AUClast (area under the plasma concentration-time curve from time zero to time of last quantifiable concentration) of the acalabrutinib NG suspension when coadministered with the PPI in participants with COVID-19
• Acalabrutinib and ACP-5862 plasma PK parameter: Cmax [ Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, and 12 hours post-dose ]
  To assess the Cmax (maximum observed plasma concentration) of the acalabrutinib NG suspension when coadministered with the PPI in participants with COVID-19
• Type, frequency, severity, and relationship to study intervention of any treatment-emergent AEs or abnormalities of laboratory tests, SAEs, or AEs leading to discontinuation of study intervention [ Time Frame: From screening to 28 days (+/- 3days) after last dose of acalabrutinib ]
  To Assess Safety and tolerability of acalabrutinib suspension in participants with COVID-19 when administered in the presence of PPIs and BSC

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: July 31, 2020)

• Proportion of participants alive and free of respiratory failure at Days 14 and 28 [ Time Frame: 28 Days ]
  To evaluate the preliminary efficacy of adding acalabrutinib suspension to BSC for treatment of participants with COVID-19
• Percent change from baseline in CRP at Days 3, 5, 7, 14, 28 [ Time Frame: Baseline and Days 3, 5, 7, 14, 28 ]
  To evaluate the preliminary efficacy of adding acalabrutinib suspension to BSC for treatment of participants with COVID-19
• Time to improvement- clinical improvement of ≥ 2 points(from first dose date)on a 9-point category ordinal scale Or live discharge from the hospital Or considered fit for discharge(a score of 0,1,or2 on the ordinal scale)whichever comes first,by Day 28 [ Time Frame: Up to Day 28 ]
  To evaluate the preliminary efficacy of adding acalabrutinib suspension to BSC for treatment of participants with COVID-19

• 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 in Participants Hospitalized With COVID-19
• Official Title: An Open-label, Multiple-dose Study of Acalabrutinib, Co Administered With a Proton-pump Inhibitor, in Participants Hospitalized With COVID-19
• Brief Summary: Study D822FC00005 will investigate the Phamacokinetics, Safety and tolerability of Acalabrutinib suspension when delivered via a nasogastric tube and co-administered with a Proton Pump Inhibitor, in the treatment of COVID-19.
• Detailed Description: This study is to support the ongoing clinical development of acalabrutinib (CALQUENCE®) in hospitalized COVID-19 patients. Because many COVID-19 patients may be unable to swallow capsules due to respiratory failure (eg, they may require endotracheal intubation for ventilator support and Naso Gastric tube placement), it is important to have a clinically acceptable method to administer acalabrutinib (capsules) via NG tube. Furthermore, many hospitalized patients are placed on high doses of proton pump inhibitors (PPIs) (also commonly known as antacid medication). This study is designed to determine the Pharmaco Kinetics (effect of body/ bodily systems on the drug), safety and tolerability of acalabrutinib suspension, when coadministered with a PPI, in participants with confirmed SARS-CoV-2 infection requiring hospitalization due to respiratory failure, attributable to COVID-19 pneumonia and who have an Nasogastric (NG) tube in place.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Single group multi dose study. Participants to receive Acalabrutinib + PPI and Best Supportive Care.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: COVID-19

Intervention

Drug: Acalabrutinib

Acalabrutinib (CALQUENCE®) is a covalent BTK inhibitor

Other Name: CALQUENCE®

Study Arms

Single Arm

Single Arm

Intervention: Drug: Acalabrutinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 29, 2021): 9
• Original Estimated Enrollment (submitted: July 31, 2020): 20
• Actual Study Completion Date: November 18, 2020
• Actual Primary Completion Date: November 18, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Participant or legally authorized representative must be able to understand the purpose and risks of the study and provide written informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).

2. Participants who are hospitalized with coronavirus (SARS-CoV-2) infection, confirmed by PCR test or other commercial or public health assay in any specimen, as documented by either of the following:

   1. PCR positive in sample collected < 72 hours prior to first dose, OR

   2. PCR positive in sample collected ≥ 72 hours prior to first dose (but no more than 14 days prior to first dose), documented inability to obtain a repeat sample (eg, due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc), AND progressive disease suggestive of ongoing SARS-CoV-2 infection 3 Evidence of respiratory failure attributable to COVID-19 pneumonia (documented radiographically) before enrollment 4 Nasogastric tube or other types of oral or percutaneous gastric feeding tube; placement must be radiographically confirmed and expected to remain in place, as judged by the investigator, for a minimum of 3 days after study enrolment.

      5 Has received treatment with PPIs (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole) for a minimum of 24 hours immediately prior to enrollment; any PPI will be permitted, provided it meets the minimum equivalent daily dose of 20 mg rabeprazole.

      Exclusion Criteria:

      1. Any serious and uncorrectable medical condition or abnormality of clinical laboratory tests that, in the Investigator's judgment, precludes the participant's safe participation in and completion of the study.
      2. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments.
      3. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
      4. Received BTK inhibitor within 7 days before enrollment.
      5. Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days prior to enrollment. Other anticoagulants are permitted.
      6. Participants on dual antiplatelet and therapeutic anticoagulant therapy (eg, aspirin and therapeutic doses of low molecular weight heparin are not allowed; however, aspirin and prophylactic/ low doses of low-molecular-weight heprin are allowed).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT04497948
• Other Study ID Numbers: D822FC00005
• Has Data Monitoring Committee: No

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

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