E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 patients suffering from moderate to severe pneumonia |
COVID-19 pacienti trpící středně těžkou až těžkou pneumónií. |
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E.1.1.1 | Medical condition in easily understood language |
COVID-19 patients suffering from moderate to severe pneumonia |
COVID-19 pacienti trpící středně těžkou až těžkou pneumónií. |
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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 | PT |
E.1.2 | Classification code | 10035664 |
E.1.2 | Term | Pneumonia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
Part A: To evaluate safety and tolerability of repeated dose of BAZE-X1 administered three times daily. Part B: To evaluate safety and tolerability of repeated dose of BAZE-X1 administered three times daily compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
Part A: To assess efficacy of repeated dose of BAZE-X1 administered three times daily. To assess PK profile and efficacy of repeated dose of BAZE-X1 administered three times daily. Part B: To assess efficacy of repeated dose of BAZE-X1 administered three times daily. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Women or men aged between 18 and 64; 2. Presence of COVID-19 pneumonia (Chest X-ray or CTPA evidence, as assessed by the treating physician); 3. Patient is admitted to hospital due to COVID-19 pneumonia; 4. Laboratory-confirmed SARS-CoV-2 infection (e.g., by PCR, antigen); 5. The patient's ability to cooperate and express his/her consent with the study participation; 6. Women of childbearing potential must have a negative pregnancy test (urine or serum) at screening and must agree to use highly effective contraceptive method from the day of enrollment in the study until 7 days (5 half-lives of bazedoxifene) after the last administered dose of IMP. As highly effective contraceptive method is considered: a. implantable intrauterine device (excluding hormone release system) b. bilateral tubal occlusion in females c. vasectomized male/partner d. sexual abstinence 7. Non-fertile man or fertile man who agree with sexual abstinence or using condom from the day of enrollment in the study until 7 days (5 half-lives of bazedoxifene) after the last administered dose of IMP; 8. Signed Informed Consent Form for participation in the study. |
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E.4 | Principal exclusion criteria |
1. Need of mechanical pulmonary ventilation (invasive / non-invasive) at study entry; 2. Need of ECMO at study entry; 3. Known hypersensitivity to the active substance or excipients; 4. Pregnancy and breast-feeding; 5. Patients with ongoing uncontrolled cardiac, metabolic, endocrinological, hepatic, renal, neurological or psychiatric illness, in whom participation in a clinical trial could pose an additional risk according to the investigator’s assessment; 6. Positive result on HIV, hepatitis A, B or C at screening; 7. Active tuberculosis infection at screening; 8. Known bacterial or fungal infection at screening; 9. Participation in another interventional treatment study with an investigational product within 30 days, or 5 half-lives, whichever is longer, prior to the planned first study treatment administration or use of other investigational product during this study; 10. Presence of hematological or generalized solid malignancy; 11. Presence of pulmonary embolism; 12. Hepatic impairment assessed individually by the investigator, ALT and/or AST levels ≥ 5x ULN at screening and baseline; 13. On active therapy with IL-6R / IL-6 / JAK / IL-1R / IL-1 inhibitor; 14. Previous receipt of IL-6R / IL-6 / JAK / IL-1R / IL-1 targeted therapy within 30 days, or 5 half-lives, whichever is longer, prior to the planned first study treatment administration; 15. Treatment with convalescent plasma; 16. Absolute Neutrophil Count (ANC) less than 500/µl at screening and baseline; 17. Platelet count of less than 50 000/µl at screening and baseline; 18. History of any severe allergy affecting respiratory system; 19. Previous participation in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A: Safety and tolerability of single dose level of BAZE-X1 administered three times daily in patients with COVID-19 pneumonia measured by incidence and spectrum of all adverse events. Part B: Safety and tolerability of single dose level of BAZE-X1 administered three times daily in patients with COVID-19 pneumonia measured by incidence and spectrum of all adverse events. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
D28 (End of trial for the subject) |
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E.5.2 | Secondary end point(s) |
Part A: Pharmacokinetic profile of BAZE-X1 measured by plasma concentrations at pre-dose before first and last administered dose and 10 minutes after first and last administered dose. Part A and B: Efficacy of BAZE-X1 on prevention of cytokine storm measured by change in leukocyte, lymphocyte, neutrophil count and plasma concentration of CRP, D/dimers, ferritin and IL-6 at EoT compared to baseline (D1). Efficacy of antiviral effect of BAZE-X1 measured by change in concentration of N (nucleocapsid) antigen in blood at EoT compared to baseline (D1). Efficacy of BAZE-X1 in patients with COVID-19 pneumonia measured by number of respiratory (invasive / non-invasive mechanical ventilation) and cardiovascular (infusion of vasopressor/inotrope at any dose) support free days within 28 days of study period, calculated from baseline (D1) to discharge or last follow-up (D28). Efficacy of BAZE-X1 measured by number of days on supplementary oxygen therapy (face mask up to 15 L/min) within 28 days of study period, calculated from baseline (D1) to discharge or last follow-up (D28). Efficacy of BAZE-X1 measured by number of days on HFNC (high-flow nasal cannula devices) within 28 days of study period, calculated from baseline (D1) to discharge or last follow-up (D28). Efficacy of BAZE-X1 in patients administered with oxygen (supplementary oxygen therapy or HFNC) at the baseline (D1) measured by the change in oxygen flow (L/min) at D28 or day of discontinuation of oxygen administration if earlier, compared to baseline (D1). Efficacy of BAZE-X1 measured by hospital discharge time within 28 days of study period, calculated from baseline (D1) to discharge or last follow-up (D28). Efficacy of BAZE-X1 measured by change in P/F ratio at EoT compared to baseline (D1). Hospital mortality at D28. Efficacy measured by changes in Clinical status of patient (using 7-point ordinal scale): at baseline (D1), EoT and D28. - Death - Hospitalized, on invasive mechanical ventilation or ECMO - Hospitalized, on non-invasive ventilation or high flow oxygen devices - Hospitalized, requiring supplemental oxygen - Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) - Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical Care - Not hospitalized. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
D28 (End of trial for the subject) For pharmacokinetic evaluation endpoint at D3 to D5 (End of treatment) |
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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 | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
2-parts (Part A: open label non-randomized; Part B: double blinded randomized placebo controlled) |
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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 | 3 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |