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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

Trial Profile

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

Status: Recruiting
Phase of Trial: Phase II/III

Latest Information Update: 03 Sep 2020

At a glance

  • Drugs Sarconeos (Primary)
  • Indications COVID 2019 infections; Respiratory insufficiency
  • Focus Registrational; Therapeutic Use
  • Acronyms COVA
  • Sponsors Biophytis
  • Most Recent Events

    • 01 Sep 2020 According to a Biophytis media release, the first patient has been dosed at AZ Sint Maarten hospital in Mechelen, Belgium. The trial now has five centers ready for patients recruitment in Belgium, France and the US.
    • 06 Aug 2020 Planned number of patients changed from 310 to 465.
    • 03 Aug 2020 According to a Biophytis media release, Ludhmila Abrahaao Hajjar, MD, PhD, Professor at the Faculty of Medicine University of Sao Paulo, (InCor HCFMUSP, Sao Paulo, Brazil), is COVA's Principal Investigator and National Coordinator in Brazil.

Trial Overview

Purpose

This phase II/III, adaptive and seamless 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).

Primary Endpoints

End-of-Part 1 interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.

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 Requiring high-flow oxygen
time_frame: up to 28 days

For part-2 sample size interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.

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 high-flow oxygen
time_frame: up to 28 days


For the final analysis: Proportion of subjects with all cause mortality or respiratory failure.

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 Requiring high-flow oxygen
time_frame: up to 28 days

Other Endpoints

Interim analysis; indication of activity of BIO101: Oxygen saturation by pulse oximetry (SpO2) SpO2 / Fraction of inspired oxygen (FiO2) ratio

description: • SpO2/FiO2
time_frame: 28 days

Interim analysis; indication of activity of BIO101: Inflammatory markers

description: • Inflammatory markers including:
IL 6
TNFα
D-dimer
time_frame: 28 days

Interim analysis; indication of activity of BIO101: Renin Angiotensin System biomarkers

description: • Renin Angiotensin System biomarkers:
Angiotensin 2
Angiotensin-converting enzyme (ACE) levels
time_frame: 28 days

Key secondary endpoint for final analysis: Proportion of participants with positive or negative events

description: 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
time_frame: 28 days

Additional secondary endpoints for final analysis: Respiratory function

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 in participants entering the study on low flow oxygen)
time_frame: 28 days

Additional secondary endpoints for final analysis:proportion of patients who experienced positive event

description: 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
time_frame: 28 days

Additional secondary endpoints for final analysis:proportion of patients who experienced negative events

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; 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)
time_frame: 28 days

Additional secondary endpoint for final analysis: The National Early Warning Score 2 (NewS2)

description: National Early Warning Score 2 (NewS2): scores: 0-7
time_frame: 28 days

Additional secondary endpoint for final analysis: Population Pharmacokinetics study (pop-PK)

description: Cmax: Peak Plasma concentration
time_frame: 1day

Additional secondary endpoint : Population Pharmacokinetics study (pop-PK)

description: tmax: Time to reach peak plasma concentration
time_frame: 1 day

Secondary endpoint: Population Pharmacokinetics study (pop-PK)

description: AUC: Area under the plasma concentration versus time curve
time_frame: 1 day [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Respiratory insufficiency treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 465

  • Sex male & female
  • Age Group ≥ 55 years; adult; elderly

Patient 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.

Patient 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

Trial Details

Identifiers

Identifier Owner
NCT04472728 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001498-63 European Clinical Trials Database
BIO101CL05 -

Organisations

  • Sponsors Biophytis
  • Affiliations Biophytis

Trial Dates

  • Initiation Dates

    Actual : 16 Jun 2020

  • Primary Completion Dates

    Planned : 01 Jul 2021

  • End Dates

    Planned : 01 Sep 2021

Other Details

  • Design double-blind; multicentre; prospective; randomised; sequential
  • Phase of Trial Phase II/III
  • Location Belgium; Brazil; Europe; France; United Kingdom; USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
SarconeosPrimary Drug Oral Capsule

BIO101

BIO101 350 mg bid
Drug: BIO101 (BIO101 capsules) Other Name: Sarconeos (BIO101)

Placebo

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

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Capucine Morelot-Panzini, MD Département R3S GHU APHP-Sorbonne Université, Pitié Salpetrière
-
Capucine Morélot-Panzini, MD Unité ambulatoire Service de Pneumologie, Médecine Intensive et Réanimation (SPMIR) 47-83 Boulevard de l'Hôpital France
Jean Martinot, MD
martinot.j@respisom.be
show details
CHU CLU Namur (Saint-Elisabeth) Place Louise Godin Belgium
Ludhmila Abrahão Hajjar, MD Avenida Dr. Enéas de Carvalho Aguiar, 44 - Centro de Pesquisa Clínica Prof. Dr. Fúlvio Pileggi - Bloco 1 - 1º Andar Brazil
Muriel Lins, MD
+3215892040 muriel.lins@Emmaus.be
show details
AZ-Sint Maarten Belgium
Otis Barnum, MD Barnum Medical Research, Inc. 1029 Keyser Ave Suite H USA
Shmuel Agus, MD
+16176424891 sam.agus@biophytis.com
show details
-
Valerie Pourchet, MD Hôpital Pitié-Salpêtrière, 47 bd de l'Hôpital, 75013 Paris France
Waly Dioh, PhD
+33144272339 waly.dioh@biophytis.com
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Avenida Dr. Enéas de Carvalho Aguiar, 44 - Centro de Pesquisa Clínica Prof. Dr. Fúlvio Pileggi - Bloco 1 - 1º Andar São Paulo Brazil
AZ-Sint Maarten Mechelen Belgium
Barnum Medical Research, Inc. 1029 Keyser Ave Suite H Natchitoches, Louisiana USA
Biophytis S.A.
+33(0)144 27 23 87
B.5.6 E-mail mounia.chabane@biophytis.com
show details
-
-
CHU CLU Namur (Saint-Elisabeth) Place Louise Godin Namur Belgium
Département R3S GHU APHP-Sorbonne Université, Pitié Salpetrière
-
-
Hôpital Pitié-Salpêtrière, 47 bd de l'Hôpital, 75013 Paris Paris France
Unité ambulatoire Service de Pneumologie, Médecine Intensive et Réanimation (SPMIR) 47-83 Boulevard de l'Hôpital Paris, Paris Cedex 13 France

Trial History

Event Date Event Type Comment
03 Sep 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 03 Sep 2020
01 Sep 2020 Other trial event According to a Biophytis media release, the first patient has been dosed at AZ Sint Maarten hospital in Mechelen, Belgium. The trial now has five centers ready for patients recruitment in Belgium, France and the US. Updated 04 Sep 2020
06 Aug 2020 Other trial event Planned number of patients changed from 310 to 465. Updated 06 Aug 2020
06 Aug 2020 Other trial event Last checked against European Clinical Trials Database record. Updated 06 Aug 2020
03 Aug 2020 Other trial event According to a Biophytis media release, Ludhmila Abrahaao Hajjar, MD, PhD, Professor at the Faculty of Medicine University of Sao Paulo, (InCor HCFMUSP, Sao Paulo, Brazil), is COVA's Principal Investigator and National Coordinator in Brazil. Updated 05 Aug 2020
03 Aug 2020 Other trial event According to a Biophytis media release, the company has received approval from the Brazilian Health Regulatory Agency, ANVISA (Agencia Nacional de Vigilancia Sanitaria), to start its clinical development program COVA in Brazil. Updated 05 Aug 2020
27 Jul 2020 Other trial event According to a Biophytis media release, the first part of the COVA study, which has already started in Belgium, the UK, and the USA, will provide the company with important preliminary data as the company works to confirm that Sarconeos (BIO101) can successfully prevent the deterioration of the respiratory function in Covid-19 patients. Updated 04 Aug 2020
27 Jul 2020 Other trial event According to a Biophytis media release, the study is to start in France mostly with the La Pitie-Salpetriere Hospital, which is linked with Sorbonne Universitys medical school, a long-standing partner of Biophytis. The authorization comes at a crucial moment of COVID-19 upsurge in France and in Europe, re-emphazing the emergency of finding innovative treatments against the pandemics. Updated 04 Aug 2020
27 Jul 2020 Other trial event According to a Biophytis media release, the second interim analysis will be conducted half way of the second part and will assess the final size of the cohort, estimated at this stage to 310 patients. Updated 04 Aug 2020
27 Jul 2020 Other trial event According to a Biophytis media release, the first interim analysis will be conducted when the first 50 participants finish the study intervention period. Upon the green light to proceed, delivered by the DMC based on safety data, the Company can then continue recruiting into the second part. This analysis can also provide an initial proof of activity of Sarconeos (BIO101) on the study participants. Updated 04 Aug 2020
27 Jul 2020 Other trial event According to a Biophytis media release, the COVA study is an adaptive study with 2 planned interim analyses that will be conducted by an independent data-monitoring committee (DMC). Updated 04 Aug 2020
27 Jul 2020 Other trial event According to a Biophytis media release, this is a two-stage study that will be coordinated by Dr. Capucine Morelot-Panzini, Professor of Pulmonology at the Pitie-Salpetriere University Hospital in Paris and Principal Investigator of COVA in France. Updated 04 Aug 2020
27 Jul 2020 Other trial event According to a Biophytis media release, this phase 2/3, adaptive and seamless study is expected to start in the coming weeks in France. Updated 04 Aug 2020
27 Jul 2020 Other trial event According to a Biophytis media release, the company has received approval from the French National Agency for the Safety of Medicines and Health Products (ANSM) to proceed with its clinical development program: COVA. The program will assess Sarconeos (BIO101) as a potential treatment for acute respiratory failure associated with COVID-19. Updated 04 Aug 2020
17 Jul 2020 Other trial event New source identified and integrated(ClinicalTrials.gov: US National Institutes of Health;NCT04472728). Updated 17 Jul 2020
13 Jul 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 04 Aug 2020
02 Jul 2020 Other trial event According to a Biophytis media release, the company has received 6.1 euros million private placement. The company plans to used this net proceeds for the progress of this study. Updated 07 Jul 2020
01 Jul 2020 Other trial event According to a Biophytis media release, the United States (US) Food and Drug Administration (FDA) has accepted the Investigational New Drug (IND) application and received IND clearance to proceed this trial. Updated 01 Sep 2020
01 Jul 2020 Other trial event According to a Biophytis media release, company has already initiated the work to start this trial as soon as possible in the US, and in the European countries where approval has been received, and will update the market shortly on planned timelines. Updated 07 Jul 2020
11 Jun 2020 Other trial event According to a Biophytis media release, this trial is expected to start in the coming weeks in the UK, upon approval of the relevant ethics committees. Updated 12 Jun 2020
11 Jun 2020 Other trial event According to a Biophytis media release, the company has filed clinical trial applications with the FDA in the US. Updated 12 Jun 2020
11 Jun 2020 Other trial event According to a Biophytis media release, the company received approval from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) to proceed with this trial. Updated 12 Jun 2020
09 Jun 2020 Other trial event Planned number of patients changed from 545 to 310. Updated 09 Jun 2020
22 May 2020 Other trial event New source identified and integrated (European Clinical Trials Database: EudraCT2020-001498-63). Updated 22 May 2020
20 May 2020 Other trial event According to a Biophytis media release, the company expects to start this trial in the coming weeks in Belgium and plans to expand the trial at multiple sites in Europe and US pending potential approvals from the ANSM, MHRA and FDA. Updated 22 May 2020
20 May 2020 Other trial event According to a Biophytis media release, an interim analysis conducted by an independent Data Monitoring Committee (DMC) is expected in the 4th quarter of this year, subject to the evolution of the COVID-19 epidemic, will determine whether the study should progress into the second part and will allow recruitment of required sample size needed for detecting Sarconeos (BIO101) effects in part 2. Updated 22 May 2020
20 May 2020 Other trial event According to a Biophytis media release, Dr Muriel Lins (Pulmonologist at AZ Sint Maarten hospital in Mechelen) is the Principal Investigator of COVA in Belgium. Updated 22 May 2020
20 May 2020 Other trial event According to a Biophytis media release, the company has received approval from the Belgian regulatory agency, the Federal Agency for Medicines and Health Products (FAMHP), to proceed with this trial. Updated 22 May 2020
08 Apr 2020 New trial record New trial record Updated 08 Apr 2020
07 Apr 2020 Other trial event According to a Biophytis media release, it has secured a new line of financing that could reach 24 million euros, raised from Atlas, a specialized investment fund based in New York (United States) which will enable it to continue the clinical development of this trial Updated 15 Apr 2020
07 Apr 2020 Other trial event According to a Biophytis media release, the first randomized patient is expected to be recruited at the Pitie-Saletriere Hospital, which is linked with Sorbonne University's medical school, a long-standing partner of Biophytis. Updated 08 Apr 2020
07 Apr 2020 Other trial event According to a Biophytis media release, the company plan to start this trial in the coming weeks following approval from the French National Agency for the Safety of Medicines and should then extend to Belgium and the United States. Updated 08 Apr 2020
07 Apr 2020 Other trial event According to a Biophytis media release, the company has filed a clinical trial application with the French Regulatory Authority (ANSM). Updated 08 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Biophytis. Biophytis Receives Approval from the French Health Authority (ANSM) to Initiate COVA, a Clinical Trial with Sarconeos (BIO101) for the Treatment of COVID-19 Related Respiratory Failure. Media-Rel 2020;.

    Media Release
  3. Biophytis. Biophytis Enrolls First Patient in COVA, a Multinational Phase 2/3 Clinical Trial with Sarconeos (BIO101) for the Treatment of Patients with COVID-19 Related Respiratory Failure. Media-Rel 2020;.

    Media Release
  4. Biophytis. Biophytis Receives Approval from Brazilian Health Regulatory Agency to Start COVA, a Phase 2/3 Clinical Trial with Sarconeos (BIO101) for the Treatment of Patients with COVID-19 Related Respiratory Failure. Media-Rel 2020;.

    Media Release
  5. Biophytis. Biophytis Receives FDA IND Clearance for COVA, a Phase 2/3 Clinical Trial with Sarconeos (BIO101) for the Treatment of Patients with COVID-19 Related Respiratory Failure. Media-Rel 2020;.

    Media Release
  6. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  7. Biophytis. Biophytis Receives Approval from the Belgian Regulatory Agency (FAMHP) to Initiate COVA, a Clinical Trial with Sarconeos (BIO101) for the Treatment of Patients with COVID19 Related Respiratory Failure. Media-Rel 2020;.

    Media Release
  8. Biophytis. Biophytis Receives MHRA Approval to Initiate the COVA Clinical Trial in the UK with Sarconeos (BIO101) for the Treatment of Patients with COVID-19 Related Respiratory Failure. Media-Rel 2020;.

    Media Release
  9. Biophytis. Biophytis Announces a 6.1 Million Capital Increase Through Private Placement. Media-Rel 2020;.

    Media Release
  10. Biophytis. Biophytis has signed a New Convertible Bond Financing of EUR24 million from Atlas to Continue the Development of Sarconeos (BIO101). Media-Rel 2020;.

    Media Release
  11. Biophytis. Biophytis Launches COVA Clinical Study with Sarconeos (BIO101) in Covid-19. Media-Rel 2020;.

    Media Release
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