E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) |
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E.1.1.1 | Medical condition in easily understood language |
Moderate COVID-19 disease leading to hospitalisation but without need of intubation |
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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 | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084270 |
E.1.2 | Term | SARS-CoV-2 acute respiratory disease |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The primary objective is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo until day 28. - Proportion of patients with worsened disease state until day 28 in both treatment groups
Progression/worsening of disease state will be defined as a worsened WHO score on 3 consecutive days (always compared to the BL WHO score) until day 28 (e.g., a WHO score of 5 on 3 consecutive days for a patient that had a WHO score of 4 at BL will be defined as a worsened disease) |
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E.2.2 | Secondary objectives of the trial |
Assessment and treatment comparison of the following objectives between the FX06 and placebo group: a)Disease progression/improvement (WHO scale score) b)Lung function (partial oxygen pressure, fraction of inspired oxygen, Horowitz index) Lung function assessments will only be documented for the study if routinely done c)Oxygen saturation and breathing rate d)Systemic inflamation blood parameters e)Survival -Proportion of patients who survived until day 28 -Proportion of patients who survived until day 60 f)Capillary refill time -Proportion of patients with normal and pathological capillary refill time at baseline (as pathological: ≥2 s or normal: <2 s) and change to BL g)Duration of hospital stay h)Drug accountability (e.g., dose, number of administrations) i)Time to SARS-CoV-2 RT-PCR negativity in respiratory tract specimen j)Subgroup analysis by concomitant medication, SARS-CoV-2 vaccination status, age and sex k)Safety |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. SARS-CoV-2 infection confirmed by PCR test 2. Hospitalised patients 3. WHO score 4-6 [28] 4. Oxygen saturation ≤ 92% under room air 5. Breathing frequency per minute ≥ 20 6. Patients ≥ 18 years 7. Written informed consent obtained prior to the initiation of any protocol-required procedures by the patient 8. Willingness to comply to study procedures and study protocol 9. Patients able to understand the requirements of the study and give written informed consent |
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E.4 | Principal exclusion criteria |
1. Significant underlying known co-morbidities or conditions, defined as: o Other severe advanced or chronic lung diseases (e.g., COPD Gold ≥ III, severe silicosis) o End-stage chronic kidney disease (stage 5) o End-stage chronic heart failure (NYHA ≥ III) o Dementia o Baseline neurologic disease which would preclude rehabilitation potential o Disseminated and/or metastasised malignancy o Severe deconditioning with a life expectancy of less than 6 months according to the treating physician o Immunocompromised patients - recipient of a solid organ transplant - regular intake of anti-inflammatory therapy due to concomitant auto- immune diseases (e.g., biologics) - primary immune deficiency 2. Evidence of other significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases with a bad prognosis that are likely to interfere with the evaluation of the patient's safety and with the study outcome as judged by the treating physician 3. Women pregnant or breastfeeding 4. Males or females of reproductive potential not willing to use effective contraception for the duration of the study period (defined as PEARL index <1 - e.g., contraceptive pill, IUD or true sexual abstinence, bilateral tubal occlusion or male partner with vasectomy; also see chapter 19.2 for guidance) 5. Current participation in another interventional clinical trial with IMP or participation within the last 30 days |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to demonstrate a difference in the proportion of patients with progressed/worsened disease state in patients receiving FX06 compared to patients receiving placebo until day 28. - Proportion of patients with worsened disease state until day 28 in both treatment groups |
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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) |
Assessment and treatment comparison of the following objectives at all available visits and time points between the FX06 and placebo group: a) Disease progression/improvement (WHO scale score) - Proportion of patients with improved or progressed disease state - Proportion of patients with each WHO score - Average change in WHO score compared to BL - Average WHO score - Proportion of patients in each disease severity state (uninfected, mild, moderate, severe, dead) - Proportion of patients who need mechanical ventilation and number of ventilation days - Proportion of patients who need ECMO and number of days on ECMO b) Lung function (partial oxygen pressure, fraction of inspired oxygen, Horowitz index) - Absolute PaO2 (mmHg) values and change compared to BL - Absolute FiO2 (mmHg, fraction of inspired oxygen) and its change to BL - Horowitz Index (mmHg) and change to BL (Lung function assessments will only be documented for the study if routinely done) c) Oxygen saturation and breathing rate - Oxygen saturation and breathing rate and change to BL - Proportion of patients reaching > 92% oxygen saturation under room air d) Systemic inflammation (changes and normalisation in troponin, procalcitonin, CRP, leukocyte count, ferritin, D-dimers, lactate, lactate dehydrogenase, albumin) - Concentration of blood parameters and their change to BL - Proportion of patients with normalized systemic inflammation (for each inflammation parameter) e) Survival - Proportion of patients who survived until day 28 - Proportion of patients who survived until day 60 f) Capillary refill time - Proportion of patients with normal and pathological capillary refill time at baseline (as pathological: ≥2 s or normal: <2 s) and change to BL g) Duration of hospital stay - Length of hospital stay until day 28 or until day 60 - Proportion of patients that have been discharged from the hospital until day 28 and day 60 - Location where patients have been discharged to (if applicable; e.g. home, rehabilitation centre) h) Drug accountability (e.g., dose, number of administrations) - Number of IMP administrations - Mean IMP dose per day and mean cumulative IMP dose SARS-CoV-2 rRT-PCR ct values and time to negativity (i.e. two consecutive negative PCR-tests as defined by each local laboratory) i) Time to SARS-CoV-2 RT-PCR negativity in respiratory tract specimen - Proportion of patients with a negative SARS-CoV-2 PCR test at day 6, 10 and 28 - Change (reduction) in SARS-CoV-ct-values j) Subgroup analysis by concomitant medication, SARS-CoV-2 vaccination status, age and sex - Proportion of patients with a specific type of concomitant medication (e.g., antibiotics, corticosteroids, antibody therapy, etc.), with different SARS-CoV-2 vaccination status (completely vaccinated, vaccinated once, not vaccinated, last vaccination more than 6 months ago), by age groups and sex - Comparison of patients with different concomitant medications, vaccination, age groups and sex status in terms of safety events and efficacy parameters k) Safety - Safety parameters (evaluated at safety set) - Number of adverse events and serious adverse events - Type and severity (mild, moderate, severe) of (serious) adverse events - Seriousness and relatedness of (S)AEs - Mean number per patient and total number of injection related (S)AEs within 1 h after injection of IMP - Treatment-related (S)AEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
BL to at all available visits and time points |
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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 | 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
| 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 | 10 |
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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Data base hard lock In order to fulfil sponsor obligations (ICH E6[R2]) by monitoring and source data verification at site to confirm data integrity and patient safety the definition LVLS/LPLV cannot be used as end of trial. The access to hospitals and isolated departments as ICUs are hindered to avoid spreading of SARS-CoV-2 infections. Therefore, site monitoring visits and site data corrections within eCRF may only be performed significantly after LVLS/LPLV. |
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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 | 9 |
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 | 9 |