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

• Sponsor: Acerta Pharma BV (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04497948
• Collaborator: AstraZeneca (Industry)
• Enrollment: 9
• Locations: 4
• Arm: 1
• Actual Duration (Months): 1.9
• Patients Per Site: 2.3
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Acalabrutinib	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• 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.Single group multi dose study. Participants to receive Acalabrutinib + PPI and Best Supportive Care.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multiple-dose Study of Acalabrutinib, Co Administered With a Proton-pump Inhibitor, in Participants Hospitalized With COVID-19
• Actual Study Start Date: Sep 21, 2020
• Actual Primary Completion Date: Nov 18, 2020
• Actual Study Completion Date: Nov 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Single Arm Single Arm	Drug: Acalabrutinib; Acalabrutinib (CALQUENCE®) is a covalent BTK inhibitor; Other Names: CALQUENCE®

Outcome Measures

Primary Outcome Measures

1. 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) [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

2. 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) [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

3. Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5) [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

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

4. 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Porto Alegre		Brazil	90035-003
2	Research Site	Ribeirão Preto		Brazil	14051-140
3	Research Site	Sao Paulo		Brazil	01321-001
4	Research Site	Sao Paulo		Brazil	01323-903

Sponsors and Collaborators

• Acerta Pharma BV
• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 4, 2020
• Statistical Analysis Plan - Jul 16, 2020

More Information

Additional Information:

• Related Info
• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Acerta Pharma BV
• ClinicalTrials.gov Identifier: NCT04497948
• Other Study ID Numbers: D822FC00005
• First Posted: Aug 4, 2020
• Last Update Posted: Nov 17, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Acerta Pharma BV: 2019 novel coronavirus disease; Acalabrutinib; Btk inhibitor
• Additional relevant MeSH terms: COVID-19; Acalabrutinib

Study Results

Participant Flow

Recruitment Details	Approximately 20 participants were planned to be enrolled to have at least 16 evaluable participants.
Pre-assignment Detail	The study enrollment was terminated early due to the termination of the Calquence COVID-19 Clinical development program (LSPC Nov 2020)

Arm/Group Title	Acalabrutinib + BSC + PPI
Arm/Group Description	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment.
Period Title: Overall Study
STARTED	9
COMPLETED	7
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Acalabrutinib + BSC + PPI
Arm/Group Description	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment.
Overall Participants	9
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.3 (10.7)
Age, Customized (Number) [Number]
< 65 years	4 44.4%
>= 65 years	5 55.6%
Sex: Female, Male (Count of Participants)
Female	4 44.4%
Male	5 55.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 77.8%
Not Hispanic or Latino	2 22.2%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Number) [Number]
WHITE	7 77.8%
BLACK OR AFRICAN AMERICAN	2 22.2%
AMERICAN INDIAN OR ALASKA NATIVE	0 0%
ASIAN	0 0%
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	0 0%
OTHER	0 0%
NOT REPORTED	0 0%

Outcome Measures

1. Primary Outcome

Title	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)
Description	To summarize the PK parameter AUC12h of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC + PPI
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

Outcome Measure Data

Analysis Population Description

Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.

Arm/Group Title	Acalabrutinib + BSC + PPI, Visit 1 on Day 1	Acalabrutinib + BSC + PPI, Visit 2 on Day 2	Acalabrutinib + BSC + PPI, Visit 3 on Day 5
Arm/Group Description	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 1 on Day 1.	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 2 on Day 2.	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 3 on Day 5.
Measure Participants	9	9	7
Acalabrutinib	524.7 (86.5)	496.5 (58.0)	201.1 (95.3)
ACP-5862	832.8 (29.3)	1228.0 (35.1)	867.1 (43.1)

2. Primary Outcome

Title	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)
Description	To summarize the PK parameter AUClast for Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI
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

Outcome Measure Data

Analysis Population Description

Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.

Arm/Group Title	Acalabrutinib + BSC + PPI, Visit 1 on Day 1	Acalabrutinib + BSC + PPI, Visit 2 on Day 2	Acalabrutinib + BSC + PPI, Visit 3 on Day 5
Arm/Group Description	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment.	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 2 on Day 2.	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment on visit 3 on Day 5.
Measure Participants	9	9	7
Acalabrutinib	490.1 (64.8)	493.7 (58.4)	193.7 (96.6)
ACP-5862	731.0 (38.4)	1228.0 (35.1)	827.9 (46.2)

3. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5)
Description	To summarize the PK parameter Cmax of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI
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)

Outcome Measure Data

Analysis Population Description

Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.

Arm/Group Title	Acalabrutinib + BSC + PPI, Visit 1 on Day 1	Acalabrutinib + BSC + PPI, Visit 2 on Day 2	Acalabrutinib + BSC + PPI, Visit 3 on Day 5
Arm/Group Description	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 1 on Day 1.	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 2 on Day 2.	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 3 on Day 5.
Measure Participants	9	9	7
Acalabrutinib	297.0 (56.7)	307.9 (51.3)	167.1 (88.7)
ACP-5862	213.1 (62.9)	316.9 (38.5)	324.2 (47.6)

Adverse Events

Time Frame	2 months
Arm/Group Title	Acalabrutinib + BSC + PPI
Arm/Group Description	Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment.
All Cause Mortality
	Acalabrutinib + BSC + PPI
	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)
Serious Adverse Events
	Acalabrutinib + BSC + PPI
	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)
Infections and infestations
Device related infection	1/9 (11.1%)	1
Pneumonia	1/9 (11.1%)	1
Pneumonia bacterial	2/9 (22.2%)	2
Investigations
Transaminases increased	1/9 (11.1%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/9 (11.1%)	1
Vascular disorders
Hypotension	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Acalabrutinib + BSC + PPI
	Affected / at Risk (%)	# Events
Total	9/9 (100%)
Blood and lymphatic system disorders
Anaemia	5/9 (55.6%)	6
Lymphopenia	2/9 (22.2%)	2
Thrombocytopenia	1/9 (11.1%)	3
Gastrointestinal disorders
Abdominal distension	2/9 (22.2%)	2
Constipation	1/9 (11.1%)	1
Diarrhoea	1/9 (11.1%)	1
Vomiting	1/9 (11.1%)	1
Infections and infestations
Fungal infection	1/9 (11.1%)	1
Infection	1/9 (11.1%)	1
Klebsiella infection	1/9 (11.1%)	1
Lower respiratory tract infection bacterial	1/9 (11.1%)	1
Pneumonia	2/9 (22.2%)	2
Pneumonia bacterial	2/9 (22.2%)	2
Urinary tract infection	1/9 (11.1%)	1
Investigations
Alanine aminotransferase increased	2/9 (22.2%)	2
Aspartate aminotransferase increased	2/9 (22.2%)	3
Hepatic enzyme increased	1/9 (11.1%)	1
Metabolism and nutrition disorders
Hyperglycaemia	1/9 (11.1%)	1
Hypernatraemia	2/9 (22.2%)	3
Hypophosphataemia	2/9 (22.2%)	2
Type 2 diabetes mellitus	1/9 (11.1%)	1
Nervous system disorders
Peripheral motor neuropathy	2/9 (22.2%)	3
Polyneuropathy	1/9 (11.1%)	1
Psychiatric disorders
Anxiety	1/9 (11.1%)	1
Renal and urinary disorders
Acute kidney injury	1/9 (11.1%)	1
Renal impairment	1/9 (11.1%)	1
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/9 (11.1%)	1
Laryngospasm	1/9 (11.1%)	1
Organising pneumonia	1/9 (11.1%)	1
Pulmonary embolism	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
Dermatitis	1/9 (11.1%)	1
Vascular disorders
Haematoma	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI shall provide copies of any materials relating to the Study, or the Developed Technologies that either intends to publish or make any presentations relating to, at least 30 days in advance of publication, submission or presentation. PI shall not include in or shall remove from any proposed publication of any Confidential Information, errors or inaccuracies; and shall withhold publication, submission for publication or presentation for 90 days from the date the Company receives the material.