E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 pneumonia and impaired respiratory function |
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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] - Respiratory Tract Diseases [C08] |
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 | 10061986 |
E.1.2 | Term | SARS |
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 |
Evaluate the effect of DFV890 in addition to SoC, compared with SoC alone on the Acute Physiology and Chronic Health Evaluation II (APACHE II) score |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of DFV890 in addition to SoC, compared with SoC alone, on inflammatory status
• To evaluate the effect of DFV890 in addition to SoC, compared with SoC alone, on clinical status
• To evaluate the safety of DFV890 in addition to SoC, compared with SoC alone
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male and female patients aged 18-80 years inclusive at screening
• Clinically diagnosed with the SARS-CoV-2 virus
• Hospitalized with COVID-19-induced pneumonia evidenced by chest Xray, computed tomography scan (CT scan) or magnetic resonance scan (MR scan), taken within 5 days prior to randomization (within 24 hours
for patients in the Netherlands)
• Impaired respiratory function, defined as peripheral oxygen saturation (SpO2) ≤93% on room air or partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) <300 millimeter of mercury (mmHg) at screening. For cities located at altitudes greater than 2500 m above sea level, these will be substituted with SpO2 <90% and PaO2/FiO2 <250 mmHg
• APACHE II score of ≥10 at time of randomization
• C-reactive protein (CRP) ≥20 mg/L and/or ferritin level ≥600 μg/L
• Body weight mass index of ≥18 to <40kg/m2
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E.4 | Principal exclusion criteria |
• Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection (besides SARS-CoV-2)
• In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment
• Intubated prior to randomization
• Previous treatment with anti-rejection and immunomodulatory drugs within the past 2 weeks, or within the past 30 days or 5 half-lives (whichever is the longer) for immunomodulatory therapeutic antibodies or prohibited drugs, with the exception of hydroxychloroquine, chloroquine or corticosteroids
•For COVID-19 infection, ongoing corticosteroid treatment is permitted at doses as per local SoC
•For non-COVID-19 disorders, ongoing corticosteroid treatment is permitted at doses up to and
including prednisolone 10 mg daily or equivalent.
•In patients in the Netherlands only, the use of hydroxychloroquine and/or chloroquine in the
past 2 weeks are exclusionary.
•Serum alanine transaminase (ALT) or aspartate transaminase (AST) >5 times upper limit of normal detected within 24 hours at screening or at baseline or other evidence of severe hepatic impairment (Child-Pugh Class C)
• Absolute peripheral blood neutrophil count of ≤1000/mm3
• Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73m2
• Patients currently being treated with drugs known to be strong or moderate inducers of isoenzyme CYP2C9 and/or strong inhibitors of CYP2C9 and/or strong inducers of cytochrome P450, family 3, subfamily A (CYP3A) and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment
• Patients with innate or acquired immunodeficiencies
• Patients who have undergone solid organ or stem cell transplantation |
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E.5 End points |
E.5.1 | Primary end point(s) |
APACHE II severity of disease score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 15 or on day of discharge (whichever is earlier) |
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E.5.2 | Secondary end point(s) |
• Serum C-reactive protein (CRP) levels
• Clinical status over time
• Proportion of participants not requiring mechanical ventilation for survival.
• Proportion of participants with at least one-point improvement from baseline in clinical status
• Number of participants with Adverse Events (AE), Serious Adverse Events (SAE), clinically significant changes in laboratory measures, and vital signs
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to day 29 after first dose |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Denmark |
Germany |
Hungary |
India |
Mexico |
Netherlands |
Peru |
Russian Federation |
South Africa |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |