E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with kidney disease who are hospitalised with COVID-19 infection with pulmonary involvement (i.e. consistent chest imaging abnormalities) and clinical deterioration (i.e increasing oxygen requirements or biochemical signs of hyperinflammation). |
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E.1.1.1 | Medical condition in easily understood language |
Patients with kidney disease or who are immunosuppressed, who also have a diagnosis of COVID19, which affects the lungs, requiring a hospital admission. |
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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 | 10023417 |
E.1.2 | Term | Kidney dysfunction |
E.1.2 | System Organ Class | 100000004857 |
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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 | 10047463 |
E.1.2 | Term | Viral infection NOS |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063321 |
E.1.2 | Term | Interleukin level |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10079637 |
E.1.2 | Term | Dependence on oxygen therapy |
E.1.2 | System Organ Class | 10041244 - Social circumstances |
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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 |
Is the drug Clazakizumab effective in treating patients with severe COVID-19 infection? |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of Clazakizumab in treating patients with COVID-19 infection
To assess the mechanistic rationale for IL6 blockade in patients who are immunosuppressed and/or have end stage kidney disease
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Hospitalised with COVID-19 infection with pulmonary involvement (i.e. consistent chest imaging abnormalities). 2. COVID-19 infection defined by as per WHO criteria (including a positive PCR of any specimen e.g., respiratory, blood, urine, stool, other bodily fluid) or detectable IgM antibody 3. Clinical deterioration following admission to hospital defined as increasing oxygen requirement and clinical signs of hyper-inflammation (raised ferritin, d-dimer, CRP) 4. >18 years of age 5. Able to give consent |
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E.4 | Principal exclusion criteria |
1. Unable to provide informed consent 2. Known severe allergic reactions to Clazakizumab 3. Active tuberculosis (TB) infection 4. Suspected active bacterial, fungal, viral, or other infection (besides COVID-19), which in the investigator’s opinion, precludes the patient's safe participation in and completion of the study. 5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 x upper limit of normal (ULN) detected within 24 hours at screening or at baseline 6. Absolute neutrophil count (ANC) < 1000/mL at screening and baseline 7. Platelet count < 50,000/mL at screening and baseline 8. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination 9. Patients with inflammatory bowel disease (except fully excised ulcerative colitis), diverticular disease (unless fully excised), or history of GI perforation 10. Able to participate in other COVID19 drug clinical trials (participation in COVID19 antiviral trials may be permitted)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is hospital discharge up to day 28. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Following administration of Clazakizumab, follow-up information about the patient will be collected every two days for the first two weeks (or until discharge or death) and then at 1 and 3 months.
Patients discharged will be reviewed at 1 and 3 months. |
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E.5.2 | Secondary end point(s) |
The secondary outcome measures are as follows and will all be measured within 28 days post administration: • Time to Clinical Improvement (national early warning score 2 (NEWS) of ≤2 maintained for 24 hours) • Incidence of mechanical ventilation • Incidence of non-invasive ventilation • Incidence of Intensive Care admission • Duration of Intensive Care admission • Duration of time on supplemental oxygen • Mortality Rate • Participants with adverse events • Change from baseline of inflammatory markers (including Ferritin, Lactate dehydrogenase, D-Dimer, C-Reactive Protein, IL-6 and other cytokines), measured at least twice during the first 2 weeks post administration |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The following information will be collected every 2 days for the first 2 weeks post treatment administration (or until discharge or death).
Outcome status (alive/dead), hospitalisation status (inpatient/discharge), use of ventilation and use of new renal replacement therapy will also be collected at the time of death or discharge or at 28 days after treatment (whichever is sooner). |
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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 | 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) | 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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 trial will be the last visit of the last participant 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 | 1 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 1 |