E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 24.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10085775 |
E.1.2 | Term | Laboratory confirmed COVID-19 |
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 overarching goal of the trial is to find effective strategies for inpatient management of patients with COVID-19. Therapeutic goals for patients hospitalized for COVID-19 include hastening recovery and preventing progression to critical illness, multiorgan failure, or death. Our objective is to determine whether modulating the host tissue response improves clinical outcomes among patients with COVID-19.
The overarching objective of this platform is to iteratively test treatment strategies targeting the host tissue response for improving clinical outcomes among adults hospitalized with COVID-19. Treatment strategies will be added to the current best practice and tested against best practice plus placebo. Best practice may itself be updated as therapies become available or are shown to be effective (or ineffective). |
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E.2.2 | Secondary objectives of the trial |
A further objective is to determine which of the different RAAS agents’ targets (AT1r biased agonist, Ang[1-7] infusion) and associated mechanisms of action, when added to current best practice and compared to current best practice plus placebo, result in an effective therapeutic approach to the RAAS system in patients infected with SARS-CoV-2. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Hospitalized for COVID-19 2. ≥18 years of age 3. SARS-CoV-2 infection, documented by: a) a nucleic acid test (NAT) or equivalent testing within 3 days prior to randomization OR b) documented by NAT or equivalent testing more than 3 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection per the responsible investigator (For non-NAT tests, only those deemed with equivalent specificity to NAT by the protocol team will be allowed. A central list of allowed non-NAT tests is maintained in Appendix E.) 4. Hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy 5. Symptoms or signs of acute COVID-19, defined as one or more of the following: a) cough b) reported or documented body temperature of 100.4o F or greater c) shortness of breath d) chest pain e) infiltrates on chest imaging (x-ray, CT scan, lung ultrasound) |
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E.4 | Principal exclusion criteria |
1. Onset of COVID-19 symptoms fulfilling inclusion criterion #5 >14 days prior to randomization 2. Hospitalized with hypoxemia (as defined in inclusion #4) for >72 hours prior to randomization (the 72-hour window for randomization begins when the patient first meets the hypoxemia inclusion criteria after hospital admission) 3. Pregnancy 4. Breastfeeding 5. Prisoners 6. End-stage renal disease (ESRD) on dialysis 7. Patient undergoing comfort care measures only such that treatment focuses on end-of-life symptom management over prolongation of life. 8. The treating clinician expects inability to participate in study procedures or participation would not be in the best interests of the patient 9. Known allergy/hypersensitivity to IMP or its excipients
Fostamatinib Arm-Specific Exclusion Criteria: 1. Randomized in another trial evaluating fostamatinib in the prior 30 days Fostamatinib Arm-Specific Exclusion Criteria measured within 24-hours prior to randomisation: 1. AST or ALT ≥ 5 × upper limit of normal (ULN) or ALT or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN 2. SBP > 160 mmHg or DBP > 100 mmHg at the time of screening and randomization 3. ANC < 1000/mL 4. Patient is anticipated to require a strong CYP3A inhibitor (Atazanavir, Certinib, Clarithromycin, Cobicistat and cobicistat-containing coformulations, Idelalisib, Indinavir, Itraconazole, Ketoconazole, Levoketoconazole, Lonafarnib, Lopinavir, Mifeprostone, Mibefradil, Nefazodone, Nelfinavir, Ombitasvir-paritaprevir-ritonavir plus dasabuvir, Posaconazole, Ribociclib Ritonavir, Saquinavir, Telithromycin, Troleandomycin, Tucatinib, Voriconazole) from randomization to 21 days post-randomization. For a full list of CYP3A4 substrates, please reference this regularly updated list: https://drug-interactions.medicine.iu.edu/MainTable.aspx. 5. Patient unable to participate or declines participation in the fostamatinib arm. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of oxygen-free days at day 28. |
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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) |
• Alive and oxygen free at days 14 and 28 • Alive and respiratory failure-free at days 14 and 28 • Alive and free of new invasive mechanical ventilation at 14 and 28 days • In-hospital, 28-day, 60-day and 90-day mortality • WHO 8-point ordinal scale at 14, 28 and 60 days • Support-free days to Day 28, including: Hospital-free days Respiratory failure-free days Ventilator-free days |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 20 |
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 |
Argentina |
Brazil |
France |
Germany |
Italy |
South Africa |
Spain |
United Kingdom |
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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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The “end of the trial” occurs when patient enrolment, follow-up, data cleaning and analysis have been completed |
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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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |