Study in Hospitalized COVID-19 patients with Acalabrutinib along with the Best Supportive Care versus Best Supportive Care

Phase 2

Not yet recruiting

• Conditions: Acute respiratory failure, (2) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,

• Registration Number: CTRI/2020/06/026228
• Lead Sponsor: Acerta Pharma BV

Brief Summary

This study is multicentre, randomized, open-label, Phase 2 study that will evaluate acalabrutinib plus BSC versus BSC in subjects with COVID-19 who are hospitalized. The purpose of this Phase 2 study is to evaluate the preliminary efficacy and safety of adding acalabrutinib to best supportive care (BSC) for subjects with life-threatening COVID-19 symptoms.

Approximately, 140 patients would be randomized in the study and Subjects will be randomly assigned (1:1) to receive one of the following 2 treatments: Arm 1: Acalabrutinib  BSC (n=70) and Arm 2: BSC alone (n=70)

For the purpose of this study, BSC is per discretion of the Investigator and institutionalguidelines (however there are few prohibited or restricted concomitant medications). Subjects will be randomized based on the following stratification factors, which are considered prognostic factors for poor outcome: Age (≥ 65 vs < 65 years); Comorbidities (present vs absent). “Present†is defined as having at least 1 of the following comorbidities: Cardiovascular disease, as defined by either heart failure New York Heart Association class ≥2 or hypertension requiring treatment; Diabetes mellitus requiring treatment; Chronic obstructive pulmonary disease or asthma requiring treatment; Current active solid tumor or hematologic malignancy.

 Acalabrutinib will be administered for a maximum of 10 days. BSC will be administered across all arms per Investigator’s discretion and institutional guidelines. Subjects who have respiratory failure before completing the maximum treatment period will be permitted to continue treatment with acalabrutinib for the maximum treatment period, according to the Investigator’s clinical judgment. Subjects who can no longer swallow pills, such as those with nasogastric or enteral feeding tubes utilized for mechanical ventilation, will not be eligible to continue acalabrutinib treatment. Retreatment with acalabrutinib is not allowed.

 An internal Data Monitoring Committee (iDMC), independent from the Sponsor’s study team, will be established to enable early identification of safety signals in the study, minimize risk to subjects during the study, and make recommendations as to the future conduct of this study in accordance with the iDMC charter. The first safety review will occur approximately 28 days after the first 30 subjects (data cut-off) are randomized into the study. The second safety review will occur approximately 28 days after the first 80 subjects (data cut-off) are randomized into the study

 The end of study is defined as the last expected visit/contact of the last subject undergoing the study. A subject is considered to have completed the study when he/she has completed his/her last scheduled procedure. All randomized subjects will be followed for survival through 90 (± 7) days after randomization.

All subjects who discontinue the investigational study treatment for any reason other than withdrawal of consent, loss to follow-up, or death will have a safety follow up assessment 28 (± 3) days after the last dose of acalabrutinib. The study may be stopped if, in the judgment of the Sponsor, study subjects are placed at undue risk because of clinically significant findings

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2020-03-08
• Study Start: 2020-06-29

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

• 1.Ability to understand the purpose and risks of the study and provide signed and dated informed consent.
• 2.Men and women ≥18 years of age 3.SARS-CoV-2 confirmed per World Health Organization (WHO) criteria 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

• COVID-19 Related Medical Conditions 1.
• Respiratory failure at the time of screening due to COVID-19 pneumonia.
• Known medical resuscitation within 14 days of randomization.
• Any serious medical condition or abnormality of clinical laboratory tests that, in the Investigators judgment, precludes the subjects safe participation in and completion of the study 4.
• Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARSCoV2).
• In the opinion of the Investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments Medical Conditions 6.
• Not expected to survive 28 days given their pre-existing, uncorrectable medical condition.
• Pregnant or breast feeding.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin ≥ 3x upper limit of normal (ULN) and/or severe hepatic impairment (Child-Pugh class C).
• Absolute neutrophil count (ANC) < 500/μL at screening (per local laboratory).
• Platelet count < 50,000/μL at screening (per local laboratory).
• Estimated creatinine clearance of <30 mL/min calculated using the Cockcroft-Gault formula [(140age) × mass (kg)/(72 × creatinine mg/dL) multiply by 0.85 if female].
• 12.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 area allowed to enrol on study.
• 13.History of chronic hypercarbia, respiratory failure in past 6 months, or use of home oxygen in the setting of severe chronic respiratory disease.
• 14.Quadriplegia.
• 15.History of primary immunodeficiency, tuberculosis, progressive multifocal leukoencephalopathy (PML), aspergillus or other invasive mold/fungal infection, or received organ or bone marrow transplantation within 6 months of randomization.
• Prior/Concomitant Therapy: 17.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).
• 18.Requires treatment with proton-pump inhibitors.
• 19.Received oral antirejection or immunomodulatory drugs.
• 20.Active participation in other drug clinical trials or received treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization/enrolment.
• 21.Subjects at randomization who require inhaled corticosteroids or maintenance doses of more than 7.5 mg of prednisone or equivalent per day.
• 22.Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of acalabrutinib.
• 23.History of hypersensitivity (ie, allergic response) to active or inactive excipients of acalabrutinib or other Btk inhibitors.
• 24.Known cytoreductive chemotherapy treatment within 14 days of randomization.
• 25.Major surgery (as defined by the Investigator) within 4 weeks prior to randomization or still recovering from prior surgery.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The overall objective of the study is to evaluate the efficacy of adding acalabrutinib to BSC for the treatment of COVID-19.	Proportion of subjects alive and free of respiratory failure at Day 14
For the purpose of this study, respiratory failure, is defined based on resource utilization of any of the following modalities:	Proportion of subjects alive and free of respiratory failure at Day 14
(a) Endotracheal intubation and mechanical ventilation	Proportion of subjects alive and free of respiratory failure at Day 14
(b) Oxygen delivered by high-flow nasal cannula	Proportion of subjects alive and free of respiratory failure at Day 14
(c) Non-invasive positive pressure ventilation or continuous positive airway pressure	Proportion of subjects alive and free of respiratory failure at Day 14
(d) Extracorporeal membrane oxygenation	Proportion of subjects alive and free of respiratory failure at Day 14

Secondary Outcome Measures

Name	Time	Method
To evaluate the efficacy of adding acalabrutinib to BSC for the treatment of COVID-19.	Percent change from baseline in CRP
To evaluate the efficacy of adding acalabrutinib to BSC for the treatment of COVID-19	Relative change from baseline in oxygenation index (PaO2/FiO2)
Safety Objective:	To evaluate the safety of acalabrutinib in subjects with COVID-19 when administered with BSC
Safety Endpoint/Variable:	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
PK objective:	To assess PK of Acalabrutinib and its active metabolite in subjects with COVID-19 when administered with BSC
PK Endpoint/Variable:	Acalabrutinib, Cmax, tmax, t1/2, AUC 0-time, and its active metabolite, ACP-5862 Cmax, and other PK parameters (e.g. CL/F or Vdss/F) where appropriate
Exploratory Objectives:	Evaluate changes in inflammatory cytokines/chemokines associated with COVID-19
Exploratory Endpoints/Variables:	Change from baseline in cytokines/chemokines such as INFỾ, TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, MCP-1, etc

Trial Locations

Locations (5)

B.J. Medical College & Civil Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Max Smart Super Speciality Hospital; 🇮🇳 Delhi, DELHI, India

Tata Memorial Hospital; 🇮🇳 Mumbai, MAHARASHTRA, India

Vardhman Mahavir Medical College and Safdarjung Hospital (VMMC and SJH); 🇮🇳 Delhi, DELHI, India

Victoria Hospital, Bangalore Medical College and Research Institute; 🇮🇳 Bangalore, KARNATAKA, India

B.J. Medical College & Civil Hospital

🇮🇳Ahmadabad, GUJARAT, India

Dr Kartikeya Parmar

Principal investigator

09924643799

drkartik@gmail.com