E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus Disease 2019 (COVID-19) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 10053983 |
E.1.2 | Term | Corona virus infection |
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 purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injection in subjects with COVID-19. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female adult ≥ 18 years of age at time of screening. 2. Subjects hospitalized with severe or critical illness caused by coronavirus 2019 infection as defined below: Severe Illness: • Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days of screening AND • Symptoms of severe systemic illness/infection with COVID-19: o At least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe lower respiratory symptoms including dyspnea at rest or respiratory distress AND • Clinical signs indicative of severe systemic illness/infection with COVID-19, with at least 1 of the following: o RR ≥ 30, HR ≥ 125, SaO2 <93% on room air or requires > 2L oxygen by NC in order maintain SaO2 ≥93%, PaO2/FiO2 <300 AND • No criteria for Critical Illness: o None of the following: Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations), Septic shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg), Multiple organ dysfunction/failure Critical Illness: • Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing within 5 days of screening AND • Evidence of critical illness, defined by at least 1 of the following: o Respiratory failure defined based on resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (in setting of resource limitation) OR • Shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg or requiring vasopressors) OR • Multiple organ dysfunction/failure 3. Subject is not intubated (or intubated within 72 hours of the screening). If intubated, positive end-expiratory pressure (PEEP) <15 cmH2O with PaO2/FiO2 >150 mmHg. 4. Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator. Note: Below are the examples of clinically significant and non-clinically significant ECG abnormalities: − ECG findings indicative of acute myocardial infarction or acute ischemic changes would be considered clinically significant abnormalities. − ECG finding such as atrial fibrillation, atrial flutter, paced rhythms in individuals who have undergone permanent pacemaker placement, evidence of prior infarction, unchanged stable conduction abnormalities e.g. right bundle branch block, or any other finding which does not significantly impact mortality would be considered non-clinically significant findings and subjects with these abnormal findings would be allowed to enroll in the study. 5. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures. 6. Understands and agrees to comply with planned study procedures. 7. Women of childbearing potential must agree to use at least one medically accepted method of contraception (e.g., barrier contraceptives [condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or intrauterine devices) for the duration of the study. |
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E.4 | Principal exclusion criteria |
1. Subjects with do-not-resuscitate (DNR) and/or do-not-intubate (DNI) orders or expected to be made DNR/DNI in setting of resource limitations or family wishes. 2. Not a candidate for dialysis or continuation of care (or full medical support) in setting of resource limitations. 3. Subject on vasopressors for >24 hours at time of screening. 4. Subjects who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible. 5. Inability to provide informed consent or to comply with test requirements 6. Consideration by the investigator, for safety reasons, that the subject is an unsuitable candidate to receive study treatment 7. Subject participating in another study with for an investigational treatment for COVID-19. Note: Subject who were prescribed hydroxychloroquine or chloroquine with or without azithromycin for the off-label treatment of COVID-19 prior to study enrollment may be included and may continue to receive these agents. 8. Subjects who have received off-label immunomodulatory treatments for COVID-19 including but not limited to sarilumab, clazakizumab, tocilizumab, and anakinra. |
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E.5 End points |
E.5.1 | Primary end point(s) |
All-cause mortality at Day 28 |
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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) |
• All-cause mortality at Day 14 • Change in clinical status of subject at Days 14 and 28 (on a 7 point ordinal scale) A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities. • Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 14. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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) | 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 | 5 |
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 |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
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 | 2 |