E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
inflammatory lung injury associated with severe COVID-19 infection |
|
E.1.1.1 | Medical condition in easily understood language |
inflammatory lung injury associated with severe COVID-19 infection |
|
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 | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084383 |
E.1.2 | Term | Novel COVID-19-infected pneumonia |
E.1.2 | System Organ Class | 100000004862 |
|
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 effect of tradipitant in COVID-19 participants, as measured by the percentage of responders with an improvement of 2 or more points on a 7-point ordinal scale as compared to baseline. The 7‐point ordinal scale is defined as follows: 1- Death 2- Hospitalized on mechanical ventilation or ECMO 3- Hospitalized on non-invasive ventilation or high-flow oxygen supplementation 4- Hospitalized requiring supplemental oxygen 5- Hospitalized not requiring supplemental oxygen, requiring continued medical care 6- Hospitalized not requiring supplemental oxygen, not requiring continued medical care 7- Not hospitalized |
|
E.2.2 | Secondary objectives of the trial |
1. Time to response on 7-point ordinal scale 2. Time to normalization of fever for at least 48 hours 3. Time to improvement in oxygenation for at least 48 hours 4. Treatment and prevention of inflammatory lung injury as measured by inflammatory markers 5. Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples 6. In-hospital mortality 7. Mean change in NEWS2 score from baseline 8. Understand the effect of genetics for treatment response, and understand genetics of COVID-19 virus 9. Reduction from baseline of NRS for cough 10. Reduction from baseline of NRS for nausea 11. Length of hospital stay |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adults aged 18-90; 2. Confirmed laboratory COVID-19 infection; 3. Confirmed pneumonia by chest radiograph or computed tomography; 4. Fever defined as temperature ≥ 36.6 °C armpit, ≥ 37.2 °C oral, or ≥ 37.8 °C rectal since admission or the use of antipyretics; 5. PaO2 / FiO2 ≤ 300; 6. In-patient hospitalization. |
|
E.4 | Principal exclusion criteria |
1. Inability to provide informed consent or to have an authorized relative or designated person provide informed consent, or to comply with the protocol requirements; 2. Known allergy to tradipitant or other neurokinin-1 antagonists; 3. Pregnancy; 4. Uncontrolled HIV, HBV, or HCV infection; 5. Other uncontrolled medically significant diseases; 6. Enrollment in another clinical trial of an investigational therapy; 7. Alanine aminotransferase > 5X Upper Limit of Normal or Creatinine clearance < 50 ml / min; 8. Requiring mechanical ventilation for > 72 hours. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the percentage of responders at day 28, as defined by an improvement of 2 or more points on a clinical status 7-point scale as compared to baseline. The primary endpoint will be summarized in Kaplan-Meier survival curve, and the treatment difference will be tested by the log-rank test in the ITT population. The statistical analyses will be detailed in the statistical analysis plan (SAP). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The categorical secondary endpoints from other questionnaires will be analyzed by the CMH (Cochran-Mantel-Haenszel) test. The continuous secondary endpoints will be analyzed by ANOVA/ANCOVA. The Kaplan-Meier survival curve and log-rank test will be used to analyze the time to event variable. The details will be provided in the SAP. |
|
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 | 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) | No |
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 | Yes |
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 | 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 | 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 |
|
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
|
|
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 |