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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety of candidate agents as add-on therapy to standard of care in patients with COVID-19. Safety will be assessed using:
• Haematological and biochemical safety laboratory investigations (blood tests). • Physical examination • Vital signs (blood pressure/heart rate/temperature and respiratory rate) • Daily electrocardiogram (ECG) readings • Adverse events
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E.2.2 | Secondary objectives of the trial |
1) To determine what the drugs does to the body (pharmacodynamics) and what the body does to the drug (pharmacokinetics) of the proposed trial treatments in COVID-19 patients. 2) Assess the response of key exploratory biomarkers/pathways during treatment period. 3)To evaluate the improvement or deteroriation of patients in each treatment arm. 4) To evaluate the number of oxygen-free days. 5) To evaluate ventilator-free days and incidence and duration of any form of new ventilation use. 6) To evaluate the amount of virus in the patient using saliva/oropharyngeal/nose samples To evaluate time to discharge 7) Duration of total hospital stay 8) To evaluate the use of renal dialysis or haemofiltration for each treatment arm.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: Provision of informed consent from the patient or representative Aged at least 16 years If the patient is of child bearing potential*, the patient, and their partner(s), agree to use medically-accepted double-barrier methods of contraception (eg, barrier methods, including male condom, female condom or diaphragm with spermicidal gel) during the study and for at least 90 days after termination of study therapy. A vasectomised partner would be considered an appropriate birth control method provided that the partner is the sole male sexual partner and the absence of sperm has been confirmed. COVID-19 positive
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E.4 | Principal exclusion criteria |
Exclusion criteria:
• Current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled cardiac disease (NYHA class IV), uncontrolled renal disease (eGFR <30 mL/min/1.73 m2), severe liver dysfunction (ALT/AST >5x ULN) or bone marrow failure (Hb <80 g/LAND ANC<0.5 mm3 AND platelet count <50,000 uL) Women who are pregnant or breastfeeding. • Participation in another clinical trial of an investigational medicinal product (CTIMP) • Known hypersensitivity to the IMP or excipients (e.g. lactose) • Pre-existing or concomittant use of off-label treatments for COVID-19 • Significant electrolyte disturbance (hyperkalaemia K+ >5.0 mmol/L or hyponatraemia Na+ < 120mmol/L) • Patient currently receiving potassium sparing diuretics that cannot be reasonably withheld • Patient currently receving prophylactic or therapeutic anticoagulants or antiplatelet agents that cannot be reasonably withheld
• Ongoing dialysis • History of serious liver disease (Child Pugh score > 10) • Hemoglobin < 80 g/L • Any known allergy to the IMP/excipients • Severe uncontrolled diabetes mellitus • In the Investigator’s opinion, patient is unwilling or unable to comply with drug administration plan, laboratory tests or other study procedures.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety will be assessed using:
• Haematological and biochemical safety laboratory investigations. • Physical examination • Vital signs (blood pressure/heart rate/temperature and respiratory rate) • Daily electrocardiogram (ECG) readings • Adverse events
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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) |
To determine the PK/PD of the proposed trial treatments in COVID-19 patients. Assess the response of key exploratory biomarkers during treatment period.
To evaluate the improvement or deteroriation of patients in each treatment arm. To evaluate the number of oxygen-free days. To evaluate ventilator-free days and incidence and duration of any form of new ventilation use. Change in the ratio of the oxygen saturation to fraction of inspired oxygen concentration (SpO2/FiO2)
To evaluate SARS-CoV-2 viral load. To evaluate time to discharge To evaluate the use of renal dialysis or haemofiltration for each treatment arm.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For each drug, characterise the PK/PD of each drug treatment. Evaluate the change from baseline values for key exploratory biomarkers of target engagement for each treatment. Record changes to WHO ordinal scale and NEWS2 score Duration (days) of oxygen use and oxygen-free days. • Duration (days) of ventilation and ventilation-free days. • Incidence of any form of new ventilation use and duration (days) of new ventilation use. • SpO2/FiO2, measured daily from randomisation to Day 15, hospital discharge, or death Qualitative and quantitative polymerase chain reaction (PCR) determination of severe acute respiratory syndrome • Duration of total hospital stay • Duration to discharge following treatment Record requirement for renal dialysis or haemofiltration
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The end of the scheduled treatment phase is defined as the date of the last Follow-up visit of the last participant. The end of the trial is defined as the last data entry for the last participant completing the scheduled treatment phase. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |