Confirmed infection with SARS-CoV-2 (COVID-19) MedDRA version: 20.0 Level: HLT Classification code 10047465 Term: Viral infections NEC System Organ Class: 10021881 - Infections and infestations MedDRA version: 23.0 Level: PT Classification code 10084268 Term: COVID-19 System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Biophytis S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age: 55 and older. 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration >=3 days 4. With evidence of pneumonia based on all of the following: a. Clinical findings on a physical examination b. Respiratory symptoms developed within the past 7 days 5. With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: a. Tachypnea: =25 breaths per minute b. Arterial oxygen saturation =92%, on Oxygen at at least 3L/min c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion 6. Without a significant deterioration in liver function tests: a. ALT and AST = 5x upper limit of normal (ULN) b. Gamma-glutamyl transferase (GGT) = 5x ULN c. Total bilirubin = 5×ULN 7. Willing to participate and able to sign an informed consent form (ICF) 8. Female subjects should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause); OR a. Have a negative urine pregnancy test at screening b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male subjects who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of investigational product; Note: medically acceptable methods of contraception that may be used by the subject and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy. 10. Male subjects must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of investigational product; 11. For France only: Being affiliated with a European Social Security. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Not needing or not willing to remain in a healthcare facility during the entire study medication (i.e. while receiving study medication) 2. Moribund condition (death likely in days) or not expected to survive for >7 days – due to other and non-COVID-19 related conditions 3. Patient on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high flow Oxygen 4. Patient within 7 days of participating in other therapeutic clinical trial with angiotensin-converting-enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or recombinant ACE-2 5. Patient not able to take medications by mouth (as capsules or as a powder, mixed in water). 6. Disallowed concomitant medication: a. Consumption of any herbal products containing 20 hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents) 7. For patients receiving RAS pathway modulators (e.g., ACEi, ARB, or renin or aldosterone inhibitors): not on a stable regimen for at least 4 weeks prior to screening or regimen not expected to remain stable for the duration of the study. 8. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101 9. Renal disease requiring dialysis, or known renal insufficiency (eGFR=30 mL/min/1.73 m2, based on Cockroft & Gault formula) 10. In France: o Non-affiliation to compulsory French social security scheme (beneficiary or right-holder) o Being under tutelage or legal guardianship
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): For end-of-part-1 interim analysis: For safety analysis intended to facilitate the decision to begin part 2, time frame – up to 28 days: Safety and tolerability to BIO101: • SUSARs, SAEs, AESIs, AEs • Vital signs • Safety labs (including testicular biomarkers) • ECGs For interim analysis intended to obtain indication of activity of BIO101, time frame – up to 28 days: Primary: • Proportion of subjects with ‘negative’ events, of either of the following: o All-cause mortality o Respiratory failure, defined as any of the following: - Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) - Requiring ECMO - Requiring high-flow oxygen Secondary: • SpO2/FiO2 • Inflammatory markers including: o IL 6 o TNFa o D-dimer • RAS / MAS biomarkers: o Angiotensin 2 o Angiotensin-converting enzyme (ACE) levels For part-2 sample size interim analysis: For sample size re-assessment for part 2, time frame – up to 28 days: • Proportion of participants with ‘negative’ events, of either of the following: o All-cause mortality o Respiratory failure, defined as any of the following: - Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) - Requiring ECMO - Requiring high-flow oxygen For the final analysis: Primary, time frame – up to 28 days: • Proportion of participants with ‘negative’ events, of either of the following: o All-cause mortality o Respiratory failure, defined as any of the following: - Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) - Requiring ECMO - Requiring high-flow oxygen ;Timepoint(s) of evaluation of this end point: For end-of-part-1 interim analysis: For safety analysis intended to facilitate the decision to begin part 2, time frame – up to 28 days: For interim analysis intended to obtain indication of activity of BIO101, time frame | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary: • Proportion of participants with events of all-cause mortality • Proportion of participants with ‘positive’ events: o official discharge from hospital care by the department due to improvement in patient condition (self-discharge by patient is not considered a positive event) • Proportion of participants with events of respiratory failure, defined as any of the following: o Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) o Requiring ECMO o Requiring high-flow oxygen Additional secondary endpoints: • For participants who experienced a ‘positive’ event: proportion of participants with sustained positive outcome (to assess durability of effect after those participants discontinued study medication) • Time to events, of either of the following: o All-cause mortality o Respiratory failure, defined as any of the following: - Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) - Requiring ECMO - Requiring high-flow oxygen • Time to event: official discharge from hospital care due to improvement • The National Early Warning Score 2 (NewS2) • Oxygen saturation in arterial blood, measured by pulse-oximetry (SpO2) • SpO2/FiO2 • Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP in participants entering the study on low flow oxygen) • Population-PK study (pop-PK) ;Timepoint(s) of evaluation of this end point: During the trial | — |
Countries
Belgium, France, United Kingdom, United States
Contacts
Public ContactMounia Chabane De Saint Aubin
Biophytis S.A.
Outcome results
None listed