<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04472728</url>
  </required_header>
  <id_info>
    <org_study_id>BIO101-CL05</org_study_id>
    <nct_id>NCT04472728</nct_id>
  </id_info>
  <brief_title>Testing the Efficacy and Safety of BIO101 for the Prevention of Respiratory Deterioration in COVID-19 Patients</brief_title>
  <acronym>COVA</acronym>
  <official_title>Adaptive Design Phase 2 to 3, Randomized, Double-blind, to Evaluate Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BIO101 in the Prevention of the Respiratory Deterioration in Hospitalized COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biophytis</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biophytis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The COVA clinical study is a global multicentric, double-blind, placebo-controlled, group&#xD;
      sequential and adaptive 2 parts phase 2-3 study targeting in patients with SARS-CoV-2&#xD;
      pneumonia. Part 1 is a Phase 2 exploratory Proof of Concept (PoC) study to provide&#xD;
      preliminary data on the activity, safety and tolerability of BIO101 in the target population.&#xD;
      Part 2 is a phase 3 pivotal randomized study to provide further evidence of safety and&#xD;
      efficacy of BIO101 after 28 days of double-blind dosing. BIO101 is the investigational new&#xD;
      drug that activates the Mas receptor (MasR) through the protective arm of the Renin&#xD;
      Angiotensin System (RAS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Biophytis is developing BIO101, an investigational new drug, an oral preparation of&#xD;
      immediate-release 20-hydroxyecdysone (20E) at ≥ 97% purity. BIO101 activates MasR on the&#xD;
      protective arm of the Renin Angiotensin System (RAS). The engagement of MasR by BIO101 is&#xD;
      responsible for a number of preclinical beneficial activities in normal and pathological&#xD;
      contexts.&#xD;
&#xD;
      The COVA clinical study is a global, multicentric, double-blind, placebo-controlled, group&#xD;
      sequential and adaptive 2 parts phase 2-3 study in participants with SARS-CoV-2 pneumonia.&#xD;
      Part 1 is a Phase 2 exploratory Proof of Concept (PoC) study to provide preliminary data on&#xD;
      the activity, safety and tolerability of BIO101 in the target population. Part 2 is a phase 3&#xD;
      pivotal randomized study to provide further evidence of safety and efficacy of BIO101 after&#xD;
      28 days of dosing.&#xD;
&#xD;
      The trial will use an adaptive design based on pre-specified criteria, using an independent&#xD;
      external Data Monitoring Committee (DMC) to monitor safety, efficacy, and review data at&#xD;
      appropriate intervals to allow the initiation of the confirmatory part of the study.&#xD;
&#xD;
      The general objectives of the study are:&#xD;
&#xD;
        -  The purpose of Part 1 is to obtain preliminary indication of activity of BIO101, in&#xD;
           preventing respiratory deterioration in the target population (50 patients, age ≥ 55&#xD;
           years) and provide preliminary data on the safety and tolerability of BIO101 in the&#xD;
           target population&#xD;
&#xD;
        -  The purpose of Part 2 is to re-assess the sample size that is needed for the&#xD;
           confirmatory part of the study and to provide confirmation on the benefit of BIO101 and&#xD;
           safety in the larger target population (up to 310 patients)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of eligible patients due to lower number of Covid-19 cases in all involved sites.&#xD;
  </why_stopped>
  <start_date type="Actual">August 26, 2020</start_date>
  <completion_date type="Actual">September 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 6, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>End-of-Part 1 interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.</measure>
    <time_frame>up to 28 days</time_frame>
    <description>For interim analysis intended to obtain indication of activity of BIO101.&#xD;
Primary endpoint:&#xD;
• Proportion of subjects with negative events, of either of the following:&#xD;
All-cause mortality&#xD;
Respiratory failure, defined as any of the following:&#xD;
Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO</description>
  </primary_outcome>
  <primary_outcome>
    <measure>For part-2 sample size interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.</measure>
    <time_frame>up to 28 days</time_frame>
    <description>For sample size re-assessment for part 2, time frame - up to 28 days:&#xD;
• Proportion of participants with negative events, of either of the following:&#xD;
All-cause mortality&#xD;
Respiratory failure, defined as any of the following:&#xD;
Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO</description>
  </primary_outcome>
  <primary_outcome>
    <measure>For the final analysis: Proportion of subjects with all cause mortality or respiratory failure.</measure>
    <time_frame>up to 28 days</time_frame>
    <description>• Proportion of participants with of subjects with negative events, of either of the following.&#xD;
All-cause mortality&#xD;
Respiratory failure, defined as any of the following:&#xD;
Mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Interim analysis; indication of activity of BIO101: Oxygen saturation by pulse oximetry (SpO2) SpO2 / Fraction of inspired oxygen (FiO2) ratio</measure>
    <time_frame>28 days</time_frame>
    <description>• SpO2/FiO2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interim analysis; indication of activity of BIO101: Inflammatory markers</measure>
    <time_frame>28 days</time_frame>
    <description>• Inflammatory markers including:&#xD;
IL 6&#xD;
TNFα&#xD;
D-dimer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interim analysis; indication of activity of BIO101: Renin Angiotensin System biomarkers</measure>
    <time_frame>28 days</time_frame>
    <description>• Renin Angiotensin System biomarkers:&#xD;
Angiotensin 2&#xD;
Angiotensin-converting enzyme (ACE) levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Key secondary endpoint for final analysis: Proportion of participants with positive events</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>• official discharge from hospital care by the department due to improvement in participant condition (self-discharge by participant is not considered a positive event)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional secondary endpoints for final analysis: Respiratory function</measure>
    <time_frame>28 days</time_frame>
    <description>Oxygen saturation in arterial blood, measured by pulse-oximetry (SpO2) SpO2/FiO2 Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP/HFO2 in participants entering the study on low flow oxygen)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional secondary endpoints for final analysis:proportion of patients who experienced negative events</measure>
    <time_frame>28 days</time_frame>
    <description>Time to events, of either of the following:&#xD;
All-cause mortality&#xD;
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; • Proportion of participants with CPAP/BiPAP/HFO2 events, defined as requiring CPAP/BiPAP/HFO2 in participants entering the study on low flow oxygen)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional secondary endpoint for final analysis: The National Early Warning Score 2 (NewS2):</measure>
    <time_frame>28 days</time_frame>
    <description>National Early Warning Score 2 (NewS2): scores: 0-7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional secondary endpoint for final analysis: Population Pharmacokinetics study (pop-PK)</measure>
    <time_frame>1day</time_frame>
    <description>Cmax: Peak Plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional secondary endpoint : Population Pharmacokinetics study (pop-PK)</measure>
    <time_frame>1 day</time_frame>
    <description>tmax: Time to reach peak plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional secondary endpoint: Population Pharmacokinetics study (pop-PK)</measure>
    <time_frame>1 day</time_frame>
    <description>AUC: Area under the plasma concentration versus time curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional secondary endpoint: Proportion of participants with events of all-cause mortality</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Proportion of participants with events of all-cause mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional secondary endpoint: time to event: negative events</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Time to events, of either of the following:&#xD;
All-cause mortality&#xD;
Respiratory failure, defined as any of the following:&#xD;
Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage)&#xD;
Requiring ECMO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional secondary endpoint: time to event: positive events</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Time to event: official discharge from hospital care due to improvement</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">238</enrollment>
  <condition>Covid-19</condition>
  <condition>SARS-CoV2</condition>
  <arm_group>
    <arm_group_label>BIO101</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BIO101 350 mg bid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIO101</intervention_name>
    <description>BIO101 capsules</description>
    <arm_group_label>BIO101</arm_group_label>
    <other_name>Sarconeos (BIO101)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo capsules</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Sarconeos (placebo)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age: 45 and older (in France: 55 and older)&#xD;
&#xD;
          2. A confirmed diagnosis of COVID-19 infection, within the last 28 days, prior to&#xD;
             randomization, as determined by PCR or other approved commercial or public health&#xD;
             assay, in a specimen as specified by the test used.&#xD;
&#xD;
          3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection&#xD;
             symptoms with anticipated hospitalization duration &gt;=3 days&#xD;
&#xD;
             a. Patients can be included even if treated with: oxygen supplementation, High-flow&#xD;
             oxygen (HFO2), BiPAP and CPAP&#xD;
&#xD;
          4. With evidence of pneumonia based on all of the following:&#xD;
&#xD;
               1. Clinical findings on a physical examination&#xD;
&#xD;
               2. Respiratory symptoms developed within the past 14 days&#xD;
&#xD;
          5. With evidence of respiratory decompensation that started not more than 7 days before&#xD;
             start of study medication and present at screening, meeting one of the following&#xD;
             criteria, as assessed by healthcare staff:&#xD;
&#xD;
               1. Tachypnea: ≥25 breaths per minute&#xD;
&#xD;
               2. Arterial oxygen saturation ≤92%&#xD;
&#xD;
               3. A special note should be made if there is suspicion of COVID-19- related&#xD;
                  myocarditis or pericarditis, as the presence of these is a stratification&#xD;
                  criterion&#xD;
&#xD;
          6. Without a significant deterioration in liver function tests:&#xD;
&#xD;
               1. ALT and AST ≤ 5x upper limit of normal (ULN)&#xD;
&#xD;
               2. Gamma-glutamyl transferase (GGT) ≤ 5x ULN&#xD;
&#xD;
               3. Total bilirubin ≤ 5×ULN&#xD;
&#xD;
          7. Willing to participate and able to sign an informed consent form (ICF)&#xD;
&#xD;
          8. Female subjects should be:&#xD;
&#xD;
             at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence&#xD;
             of an alternative medical cause) or surgically sterile; OR&#xD;
&#xD;
               1. Have a negative urine pregnancy test at screening&#xD;
&#xD;
               2. Be willing to use a contraceptive method as outlined in inclusion criterion 9&#xD;
                  from screening to 30 days after last dose.&#xD;
&#xD;
          9. Male subjects who are sexually active with a female partner must agree to the use of&#xD;
             an effective method of birth control throughout the study and until 3 months after the&#xD;
             last administration of investigational product; Note: medically acceptable methods of&#xD;
             contraception that may be used by the subject and/or partner include combined oral&#xD;
             contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine&#xD;
             device, etonogestrel implant, each supplemented with a condom, as well as&#xD;
             sterilization and vasectomy.&#xD;
&#xD;
         10. Male subjects must agree not to donate sperm for the purpose of reproduction&#xD;
             throughout the study and until 3 months after the last administration of&#xD;
             investigational product;&#xD;
&#xD;
         11. For France only: Being affiliated with a European Social Security.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Not needing or not willing to remain in a healthcare facility during the entire study&#xD;
             medication (i.e. while receiving study medication)&#xD;
&#xD;
          2. Moribund condition (death likely in days) or not expected to survive for &gt;7 days - due&#xD;
             to other and non-COVID-19 related conditions&#xD;
&#xD;
          3. Patient on invasive mechanical ventilation via an endotracheal tube, or extracorporeal&#xD;
             membrane oxygenation (ECMO)&#xD;
&#xD;
          4. Patient within 7 days of participating in other therapeutic clinical trial with&#xD;
             angiotensin-converting-enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB)&#xD;
             or recombinant ACE-2&#xD;
&#xD;
          5. Patient not able to take medications by mouth (as capsules or as a powder, mixed in&#xD;
             water).&#xD;
&#xD;
          6. Disallowed concomitant medication:&#xD;
&#xD;
             a. Consumption of any herbal products containing 20-hydroxyecdysone and derived from&#xD;
             Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g.&#xD;
             performance enhancing agents)&#xD;
&#xD;
          7. Any known hypersensitivity to any of the ingredients, or excipients of the study&#xD;
             medication, BIO101&#xD;
&#xD;
          8. In France:&#xD;
&#xD;
               -  Non-affiliation to compulsory French social security scheme (beneficiary or&#xD;
                  right-holder)&#xD;
&#xD;
               -  Being under tutelage or legal guardianship&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Capucine Morelot-Panzini, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Département R3S GHU APHP-Sorbonne Université, Pitié Salpetrière</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Abrazo Health</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Irvine</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92697</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barnum Medical Research, Inc. 1029 Keyser Ave Suite H</name>
      <address>
        <city>Natchitoches</city>
        <state>Louisiana</state>
        <zip>71457</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beaumont Health</name>
      <address>
        <city>Royal Oak</city>
        <state>Michigan</state>
        <zip>48073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>United Health Services Hospitals</name>
      <address>
        <city>Johnson City</city>
        <state>New York</state>
        <zip>13903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>WellSpan Health</name>
      <address>
        <city>York</city>
        <state>Pennsylvania</state>
        <zip>17403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Saint-Pierre</name>
      <address>
        <city>Brussels</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Saint-Pierre</name>
      <address>
        <city>Brussel</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ-Sint Maarten</name>
      <address>
        <city>Mechelen</city>
        <zip>2800</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU CLU Namur (Saint-Elisabeth) Place Louise Godin</name>
      <address>
        <city>Namur</city>
        <zip>15 5000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Vera Cruz</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Santa Casa de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Municipal de Barueri Dr. Francisco Moran</name>
      <address>
        <city>Barueri</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital e Maternidade Celso Pierro - PUCCAMP</name>
      <address>
        <city>Campinas</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Base Da Faculdade de Medicina de São José Do Rio Preto</name>
      <address>
        <city>São José Do Rio Preto</city>
        <state>São Paulo</state>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avenida Dr. Enéas de Carvalho Aguiar, 44 - Centro de Pesquisa Clínica Prof. Dr. Fúlvio Pileggi - Bloco 1 - 1º Andar</name>
      <address>
        <city>São Paulo</city>
        <zip>103.034</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unité ambulatoire Service de Pneumologie, Médecine Intensive et Réanimation (SPMIR) 47-83 Boulevard de l'Hôpital</name>
      <address>
        <city>Paris</city>
        <state>Paris Cedex 13</state>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Argenteuil</name>
      <address>
        <city>Argenteuil</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire Bordeaux</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Rene Dubos</name>
      <address>
        <city>Cergy-Pontoise</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Départemental de Vendée</name>
      <address>
        <city>La Roche-sur-Yon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Pitié-Salpêtrière, 47 bd de l'Hôpital, 75013 Paris</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FDI Clinical Research - San Juan City Hospital</name>
      <address>
        <city>San Juan</city>
        <zip>00927</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>France</country>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>May 12, 2023</last_update_submitted>
  <last_update_submitted_qc>May 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04472728
org study id: BIO101-CL05
nct id: NCT04472728
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The COVA clinical study is a global multicentric, double-blind, placebo-controlled, group
      sequential and adaptive 2 parts phase 2-3 study targeting in patients with SARS-CoV-2
      pneumonia. Part 1 is a Phase 2 exploratory Proof of Concept (PoC) study to provide
      preliminary data on the activity, safety and tolerability of BIO101 in the target population.
      Part 2 is a phase 3 pivotal randomized study to provide further evidence of safety and
      efficacy of BIO101 after 28 days of double-blind dosing. BIO101 is the investigational new
      drug that activates the Mas receptor (MasR) through the protective arm of the Renin
      Angiotensin System (RAS).
Biophytis is developing BIO101, an investigational new drug, an oral preparation of
      immediate-release 20-hydroxyecdysone (20E) at ≥ 97% purity. BIO101 activates MasR on the
      protective arm of the Renin Angiotensin System (RAS). The engagement of MasR by BIO101 is
      responsible for a number of preclinical beneficial activities in normal and pathological
      contexts.

      The COVA clinical study is a global, multicentric, double-blind, placebo-controlled, group
      sequential and adaptive 2 parts phase 2-3 study in participants with SARS-CoV-2 pneumonia.
      Part 1 is a Phase 2 exploratory Proof of Concept (PoC) study to provide preliminary data on
      the activity, safety and tolerability of BIO101 in the target population. Part 2 is a phase 3
      pivotal randomized study to provide further evidence of safety and efficacy of BIO101 after
      28 days of dosing.

      The trial will use an adaptive design based on pre-specified criteria, using an independent
      external Data Monitoring Committee (DMC) to monitor safety, efficacy, and review data at
      appropriate intervals to allow the initiation of the confirmatory part of the study.

      The general objectives of the study are:

        -  The purpose of Part 1 is to obtain preliminary indication of activity of BIO101, in
           preventing respiratory deterioration in the target population (50 patients, age ≥ 55
           years) and provide preliminary data on the safety and tolerability of BIO101 in the
           target population

        -  The purpose of Part 2 is to re-assess the sample size that is needed for the
           confirmatory part of the study and to provide confirmation on the benefit of BIO101 and
           safety in the larger target population (up to 310 patients)
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: End-of-Part 1 interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.
time frame: up to 28 days
description: For interim analysis intended to obtain indication of activity of BIO101.
Primary endpoint:
• Proportion of subjects with negative events, of either of the following:
All-cause mortality
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
measure: For part-2 sample size interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.
time frame: up to 28 days
description: 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:
All-cause mortality
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
measure: For the final analysis: Proportion of subjects with all cause mortality or respiratory failure.
time frame: up to 28 days
description: • Proportion of participants with of subjects with negative events, of either of the following.
All-cause mortality
Respiratory failure, defined as any of the following:
Mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO
measure: Interim analysis; indication of activity of BIO101: Oxygen saturation by pulse oximetry (SpO2) SpO2 / Fraction of inspired oxygen (FiO2) ratio
time frame: 28 days
description: • SpO2/FiO2
measure: Interim analysis; indication of activity of BIO101: Inflammatory markers
time frame: 28 days
description: • Inflammatory markers including:
IL 6
TNFα
D-dimer
measure: Interim analysis; indication of activity of BIO101: Renin Angiotensin System biomarkers
time frame: 28 days
description: • Renin Angiotensin System biomarkers:
Angiotensin 2
Angiotensin-converting enzyme (ACE) levels
measure: Key secondary endpoint for final analysis: Proportion of participants with positive events
time frame: Up to 28 days
description: • official discharge from hospital care by the department due to improvement in participant condition (self-discharge by participant is not considered a positive event)
measure: Additional secondary endpoints for final analysis: Respiratory function
time frame: 28 days
description: Oxygen saturation in arterial blood, measured by pulse-oximetry (SpO2) SpO2/FiO2 Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP/HFO2 in participants entering the study on low flow oxygen)
measure: Additional secondary endpoints for final analysis:proportion of patients who experienced negative events
time frame: 28 days
description: Time to events, of either of the following:
All-cause mortality
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; • Proportion of participants with CPAP/BiPAP/HFO2 events, defined as requiring CPAP/BiPAP/HFO2 in participants entering the study on low flow oxygen)
measure: Additional secondary endpoint for final analysis: The National Early Warning Score 2 (NewS2):
time frame: 28 days
description: National Early Warning Score 2 (NewS2): scores: 0-7
measure: Additional secondary endpoint for final analysis: Population Pharmacokinetics study (pop-PK)
time frame: 1day
description: Cmax: Peak Plasma concentration
measure: Additional secondary endpoint : Population Pharmacokinetics study (pop-PK)
time frame: 1 day
description: tmax: Time to reach peak plasma concentration
measure: Additional secondary endpoint: Population Pharmacokinetics study (pop-PK)
time frame: 1 day
description: AUC: Area under the plasma concentration versus time curve
measure: Additional secondary endpoint: Proportion of participants with events of all-cause mortality
time frame: Up to 28 days
description: Proportion of participants with events of all-cause mortality
measure: Additional secondary endpoint: time to event: negative events
time frame: Up to 28 days
description: Time to events, of either of the following:
All-cause mortality
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
measure: Additional secondary endpoint: time to event: positive events
time frame: Up to 28 days
description: Time to event: official discharge from hospital care due to improvement
arm group label: BIO101
arm group type: Experimental
description: BIO101 350 mg bid
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: BIO101
description: BIO101 capsules
arm group label: BIO101
other name: Sarconeos (BIO101)
intervention type: Drug
intervention name: Placebo
description: placebo capsules
arm group label: Placebo
other name: Sarconeos (placebo)
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: No
last name: Capucine Morelot-Panzini, MD
role: Principal Investigator
affiliation: Département R3S GHU APHP-Sorbonne Université, Pitié Salpetrière
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country: Belgium
country: Brazil
country: France
country: Puerto Rico
country: United States
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No