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Testing the Efficacy and Safety of BIO101 for the Prevention of Respiratory Deterioration in COVID-19 Patients (COVA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04472728
Recruitment Status : Recruiting
First Posted : July 15, 2020
Last Update Posted : September 2, 2020
Sponsor:
Information provided by (Responsible Party):
Biophytis

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Covid-19 SARS-CoV2 Drug: BIO101 Drug: Placebo Phase 2 Phase 3

Detailed Description:

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : June 16, 2020
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : September 2021

Arm Intervention/treatment
Experimental: BIO101
BIO101 350 mg bid
Drug: BIO101
BIO101 capsules
Other Name: Sarconeos (BIO101)

Placebo Comparator: Placebo
Placebo
Drug: Placebo
placebo capsules
Other Name: Sarconeos (placebo)




Primary Outcome Measures :
  1. End-of-Part 1 interim analysis: Proportion of subjects with all cause mortality or with respiratory failure. [ Time Frame: up to 28 days ]

    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 Requiring high-flow oxygen


  2. For part-2 sample size interim analysis: Proportion of subjects with all cause mortality or with respiratory failure. [ Time Frame: up to 28 days ]

    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 high-flow oxygen


  3. For the final analysis: Proportion of subjects with all cause mortality or respiratory failure. [ Time Frame: up to 28 days ]

    • 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 Requiring high-flow oxygen



Secondary Outcome Measures :
  1. Interim analysis; indication of activity of BIO101: Oxygen saturation by pulse oximetry (SpO2) SpO2 / Fraction of inspired oxygen (FiO2) ratio [ Time Frame: 28 days ]
    • SpO2/FiO2

  2. Interim analysis; indication of activity of BIO101: Inflammatory markers [ Time Frame: 28 days ]

    • Inflammatory markers including:

    • IL 6
    • TNFα
    • D-dimer

  3. Interim analysis; indication of activity of BIO101: Renin Angiotensin System biomarkers [ Time Frame: 28 days ]

    • Renin Angiotensin System biomarkers:

    • Angiotensin 2
    • Angiotensin-converting enzyme (ACE) levels

  4. Key secondary endpoint for final analysis: Proportion of participants with positive or negative events [ Time Frame: 28 days ]
    • 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:

      • Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage)
      • Requiring ECMO
      • Requiring high-flow oxygen

  5. Additional secondary endpoints for final analysis: Respiratory function [ Time Frame: 28 days ]
    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)

  6. Additional secondary endpoints for final analysis:proportion of patients who experienced positive event [ Time Frame: 28 days ]

    For participants who experienced a positive event: proportion of participants with with sustained positive outcome (to asesss durability of effect after those participants discontinued study medication).

    Time to event: official discharge from hospital care due to improvement


  7. Additional secondary endpoints for final analysis:proportion of patients who experienced negative events [ Time Frame: 28 days ]

    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; Requiring high-flow oxygen • Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP in participants entering the study on low flow oxygen)

  8. Additional secondary endpoint for final analysis: The National Early Warning Score 2 (NewS2): [ Time Frame: 28 days ]
    National Early Warning Score 2 (NewS2): scores: 0-7

  9. Additional secondary endpoint for final analysis: Population Pharmacokinetics study (pop-PK) [ Time Frame: 1day ]
    Cmax: Peak Plasma concentration

  10. Additional secondary endpoint : Population Pharmacokinetics study (pop-PK) [ Time Frame: 1 day ]
    tmax: Time to reach peak plasma concentration

  11. Secondary endpoint: Population Pharmacokinetics study (pop-PK) [ Time Frame: 1 day ]
    AUC: Area under the plasma concentration versus time curve



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    1. Clinical findings on a physical examination
    2. 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:

    1. Tachypnea: ≥25 breaths per minute
    2. Arterial oxygen saturation ≤92%, on Oxygen at at least 3L/min
    3. 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:

    1. ALT and AST ≤ 5x upper limit of normal (ULN)
    2. Gamma-glutamyl transferase (GGT) ≤ 5x ULN
    3. 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 surgically sterile; OR

    1. Have a negative urine pregnancy test at screening
    2. 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.

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:

    • Non-affiliation to compulsory French social security scheme (beneficiary or right-holder)
    • Being under tutelage or legal guardianship

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04472728


Contacts
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Contact: Shmuel Agus, MD +16176424891 sam.agus@biophytis.com
Contact: Waly Dioh, PhD +33144272339 waly.dioh@biophytis.com

Locations
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United States, Louisiana
Barnum Medical Research, Inc. 1029 Keyser Ave Suite H Not yet recruiting
Natchitoches, Louisiana, United States, 71457
Contact: Otis Barnum, MD         
Belgium
AZ-Sint Maarten Recruiting
Mechelen, Belgium, 2800
Contact: Muriel Lins, MD    +3215892040    muriel.lins@Emmaus.be   
CHU CLU Namur (Saint-Elisabeth) Place Louise Godin Recruiting
Namur, Belgium, 15 5000
Contact: Jean Martinot, MD       martinot.j@respisom.be   
Brazil
Avenida Dr. Enéas de Carvalho Aguiar, 44 - Centro de Pesquisa Clínica Prof. Dr. Fúlvio Pileggi - Bloco 1 - 1º Andar Not yet recruiting
São Paulo, Brazil, 103.034
Contact: Ludhmila Abrahão Hajjar, MD         
France
Unité ambulatoire Service de Pneumologie, Médecine Intensive et Réanimation (SPMIR) 47-83 Boulevard de l'Hôpital Recruiting
Paris, Paris Cedex 13, France, 75651
Contact: Capucine Morélot-Panzini, MD         
Hôpital Pitié-Salpêtrière, 47 bd de l'Hôpital, 75013 Paris Recruiting
Paris, France, 75013
Contact: Valerie Pourchet, MD         
Sponsors and Collaborators
Biophytis
Investigators
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Principal Investigator: Capucine Morelot-Panzini, MD Département R3S GHU APHP-Sorbonne Université, Pitié Salpetrière
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Responsible Party: Biophytis
ClinicalTrials.gov Identifier: NCT04472728    
Other Study ID Numbers: BIO101-CL05
First Posted: July 15, 2020    Key Record Dates
Last Update Posted: September 2, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No