E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with life-threatening COVID-19 symptoms |
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E.1.1.1 | Medical condition in easily understood language |
Subjects with life-threatening COVID-19 symptoms |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The overall objective of the study is to evaluate the efficacy of adding acalabrutinib to BSC for the treatment of COVID-19 |
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E.2.2 | Secondary objectives of the trial |
To assess pharmacokinetics of acalabrutinib and its active metabolite in subjects with COVID-19 when administered with BSC
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For Part 1 (Randomized cohort):
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 COVID-19 infection confirmed per World Health Organization (WHO) criteria (including positive nucleic acid test of any specimen [eg, respiratory, blood, urine, stool, or other bodily fluid] within 3 weeks of study entry) with suspected pneumonia requiring hospitalization and oxygen saturation <94% on room air or requires 2-5 L/min of oxygen with at least one of the follow laboratory values:
(a) Ferritin > 300 ng/mL for men and > 150 ng/mL for women
(b) C-reactive protein (CRP) ≥ 10 mg/L
(c) D-dimer > 1 mg/L
(d) Absolute lymphocyte count < 1000 cells/µL
4. Able to swallow capsules or receive delivery of emptied capsule via a nasogastric (NG) or an enteral feeding tube
5. Willing to follow contraception guidelines
For Part 2 Intensive Care Unit (ICU Cohort):
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 COVID-19 infection requiring ICU admission and requiring ≥ 6 L/min of oxygen or PaO2/FiO2 ≤300 mm Hg)
4. Able to swallow capsules or receive delivery of emptied capsule via a nasogastric (NG) or an enteral feeding tube
5. Willing to follow contraception guidelines
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E.4 | Principal exclusion criteria |
For Part 1 and Part 2 (All Subjects):
1. Pregnant or breast feeding
2. Are not committed to aggressive management. For example, the subject’s family or primary physician are unwilling to place the subject on mechanical ventilation or an advanced directive to withhold life support, with the exception of cardiopulmonary resuscitation, is present.
3. Suspected, uncontrolled active bacterial, fungal, viral, or other infection (besides COVID 19)
4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 x upper limit of normal (ULN) detected within 24 hours at screening (per local lab)
5. Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, congestive heart failure (New York Heart Association [NYHA] Grade 3 or 4), or require home oxygen for a chronic lung disorder. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
6. Use of active systemic or inhaled corticosteroids. Subjects who stop active systemic or inhaled corticosteroids before the first dose of acalabrutinib will not be excluded.
7. Concomitant use of JAK, PI3K, or Btk (other than acalabrutinib) inhibitors with acalabrutinib. Subjects who stop JAK or PI3K inhibitors before the first dose of acalabrutinib will not be excluded. Use of other Btk inhibitors must be stopped 30 days before the first dose of acalabrutinib.
For Part 1:
1. In ICU or on invasive mechanical ventilation or ECMO machine before randomization.
2. Known medical resuscitation within 14 days of randomization
For Part 2:
1. Randomization to Part 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is treatment failure rate, where treatment failure is defined as use of assisted ventilation or death. For the purpose of this study assisted ventilation is defined as noninvasive ventilation (eg, continuous positive airway pressure [CPAP] ventilation), invasive mechanical ventilation, or ECMO machine |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Number of days alive free of assisted ventilation from randomization/enrollment to 30 days after randomization/enrollment
• Number of days with assisted ventilator use from randomization/enrollment to 30 days after randomization/enrollment
• Number of days hospitalized from randomization/enrollment to 30 days after randomization/enrollment
• Number of days in ICU from randomization/enrollment to 30 days after randomization/enrollment
• Number of days alive outside of hospital from randomization/enrollment to 30 days after randomization/enrollment
• Number of days alive outside of hospital from randomization/enrollment to 90 days after randomization/enrollment
• Type, frequency, severity, and relationship to study treatment of any treatment-emergent adverse events (TEAEs) or abnormalities of laboratory tests, serious adverse events (SAEs), or adverse events (AEs) leading to discontinuation of study treatment.
• Standard and appropriate pharmacokinetic parameters
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
approximately 30 days and for survival status approximately 90 days |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Italy |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |