E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects hospitalised for COVID 19 |
|
E.1.1.1 | Medical condition in easily understood language |
Subjects hospitalised for COVID 19 |
|
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 | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084382 |
E.1.2 | Term | Coronavirus disease 2019 |
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 |
art I
To evaluate the safety of a single intravenous XVR011 infusion in subjects hospitalised for COVID 19
Part II
To evaluate the efficacy of a single intravenous XVR011 infusion in subjects hospitalized for COVID-19, compared to placebo |
|
E.2.2 | Secondary objectives of the trial |
Part I
- To evaluate the efficacy of a single intravenous XVR011 infusion in subjects hospitalised for COVID-19
- To evaluate the antiviral activity of a single intravenous XVR011 infusion in subjects hospitalised for COVID-19
Part II
- To further evaluate the efficacy of a single intravenous XVR011 infusion in subjects hospitalised for COVID-19, compared to placebo
- To evaluate the antiviral activity of a single intravenous XVR011 infusion in subjects hospitalised for COVID-19, compared to placebo
- To evaluate the safety of a single intravenous XVR011 infusion in subjects hospitalised for COVID-19, compared to placebo
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Is ≥18 years of age inclusive, at the time of signing the informed consent.
- Has ongoing SARS-CoV-2 infection confirmed by positive RT-PCR test and/or positive antigen test in a timeframe consistent with the current symptoms.
- Had an onset of COVID-19 symptom(s) within 8 days prior to screening; except for dyspnoea and/or tachypnoea for which an onset within 2 days prior to screening is applicable
- Requires hospitalisation for medical care.
- Has oxygen saturation ≥ 91% (via pulse oximetry) on room air at rest.
- Informed Consent
|
|
E.4 | Principal exclusion criteria |
- Has a resting respiratory rate >= 30 per minute, or heart rate ≥ 125 per minute at hospitalisation.
- Has severe COVID-19 requiring non-invasive (e.g. high flow) or
invasive mechanical ventilation and/or intensive care treatment.
- Has ongoing clinically significant thromboembolic event or
coagulopathy, according to clinical, laboratory and/or radiological
assessment.
- Has any other medical condition, which in the opinion of the
Investigator, would impact the safety of the subjects.
- Has received an investigational or approved vaccination against SARS-CoV-2 within 14 days before study treatment start.
- Has known allergy or hypersensitivity reaction to any monoclonal
antibody or to any components of study treatment.
- For WOCBP:
o Pregnancy or a positive urine pregnancy test
o Breastfeeding
Exclusion Criteria only Applicable to Part 1
- Has received or is receiving concomitant treatment with medicinal
products with potential or demonstrated anti SARS CoV 2 (antiviral)
activity, including but not limited to remdesivir, within 30 days prior to the study treatment administration.
- Has renal impairment with estimated creatinine clearance < 60
mL/min/1.73 m2 .
- Has morbid obesity (body mass index > 35 kg/m2), uncontrolled
diabetes, cardiac insufficiency, uncontrolled high blood pressure, or any clinically significant (in the opinion of the Investigator) hepatic,
pulmonary, gastrointestinal, genitourinary, endocrine, immunologic,
metabolic, neurologic, or haematological disease.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Part I:
- Proportion of subjects with Grade ≥ 3 treatment-related AEs within 28-day FU period
- Proportion of subjects with AEs (all and serious) of any grade and independent of causality within 28-day FU period
- Proportion of subjects with infusion related reactions within 24 hours of treatment
- Proportion of subjects with hypersensitivity reactions within 28-day FU period
Part II:
- Time to recovery (i.e., clinical status reaching level 1 to 3 of the 8-point ordinal scale) within 28-day FU period
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part I and II:
within 28-day FU period |
|
E.5.2 | Secondary end point(s) |
Part I
- Time to recovery (i.e., clinical status reaching level 1 to 3 of the 8-point
ordinal scale) within 28-day FU period
- Total duration of oxygen supplementation within 28-day FU period
- Proportion of subjects requiring mechanical ventilation within 28-day FU period
- Proportion of subjects requiring ICU transfer within 28-day FU period- Time to hospital discharge
- Proportion of subjects with clinical status evolving to each level of the 8-point ordinal scale at Days 2, 3, 4, 8, 15, 22 and Day 29, compared to baseline
- Proportion of subjects with COVID-19 related symptoms
- All-cause mortality rate within 28-day FU period
- Change from baseline (Day 1 pre-dose) in the viral load (RT-qPCR) of nasopharyngeal samples at Day 1, Day3, Day 8 and day of discharge
Part II
- Total duration of oxygen supplementation within 28-day FU period
- Proportion of subjects requiring mechanical ventilation within 28-day FU period
- Proportion of subjects requiring ICU transfer within 28-day FU period- Time to hospital discharge
- Proportion of subjects with clinical status evolving to each level of the 8-point ordinal scale at Days 2, 3, 4, 8, 15, 22 and Day 29, compared to baseline
- Proportion of subjects with COVID-19 related symptoms
- All-cause mortality rate within 28-day FU period
- Change from baseline (Day 1 pre-dose) in the viral load (RT-qPCR) of nasopharyngeal samples at Day 1, Day 3, Day 8 and day of discharge
- Proportion of subjects with Grade ≥ 3 treatment-related AEs within 28-day FU period
- Proportion of subjects with AEs (all and serious) of any grade and
independent of causality within 28-day FU period
- Proportion of subjects with infusion-related reactions within 24 hours of treatment
- Proportion of subjects with hypersensitivity reactions within 28-day FUperiod |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part I:
within 28-day FU period
Part II:
within 28-day FU period
|
|
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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 |
Part 1 is open-label, single ascending dose. Part 2 is double-blind randomised, placebo-controlled |
|
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 |
Brazil |
Mexico |
South Africa |
United States |
Belgium |
France |
Italy |
Portugal |
Romania |
Spain |
United Kingdom |
|
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
|
date of the last visit of the last participant in the study |
|
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 | 0 |
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 | 0 |