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Covid-19Phase 2/3COVANCT04472728

Efficacy and Safety of BIO101 in the Prevention of Respiratory Deterioration in Hospitalized COVID-19 Patients

A Phase 2/3 study testing BIO101 in people with Covid-19 and SARS-CoV2, run by Biophytis at 22 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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 participants with SARS-CoV-2 pneumonia. Read more about this study

Who is it for?
Ages 45 years and older
Conditions the study is for
Covid-19, SARS-CoV2
What is being tested?
BIO101
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
238 participants
Where
22 sitesin 5 countries
Study dates
26 Aug 2020to 6 Jun 2022
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age: 45 and older (in France: 55 and older)
  • A confirmed diagnosis of COVID-19 infection, within the last 28 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.
  • Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration >=3 days
  • Participants can be included even if treated with: oxygen supplementation, High-flow oxygen (HFO2), bilevel positive airway pressure (BiPAP) and continuous positive airway pressure (CPAP)
  • With evidence of pneumonia based on all of the following:
  • Clinical findings on a physical examination
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  • Respiratory symptoms developed within the past 14 days
  • With evidence of respiratory decompensation that started not more than 7 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff:
  • Tachypnea: ≥25 breaths per minute
  • Arterial oxygen saturation ≤92%
  • 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
  • Without a significant deterioration in liver function tests:
  • ALT and AST ≤ 5x upper limit of normal (ULN)
  • Gamma-glutamyl transferase (GGT) ≤ 5x ULN
  • Total bilirubin ≤ 5×ULN
  • Willing to participate and able to sign an informed consent form (ICF)
  • Female participants 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
  • Have a negative urine pregnancy test at screening
  • Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose.
  • Male participants 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 participant 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.
  • Male participants 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;
  • For France only: Being affiliated with a European Social Security.

Who cannot join

  • Not needing or not willing to remain in a healthcare facility during the entire study medication (i.e. while receiving study medication)
  • Moribund condition (death likely in days) or not expected to survive for >7 days - due to other and non-COVID-19 related conditions
  • Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO)
  • Participant within 7 days of participating in other therapeutic clinical trial with angiotensin-converting-enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or recombinant ACE-2
  • Participant not able to take medications by mouth (as capsules or as a powder, mixed in water).
  • Disallowed concomitant medication:
Show all 11Show fewer
  • 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)
  • Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101
  • In France:
  • Non-affiliation to compulsory French social security scheme (beneficiary or right-holder)
  • Being under tutelage or legal guardianship

Trial locations and contacts

22 sites in 5 countries.

22 sites in 5 countries

United States6 sites

  • University of California, Irvine

    Irvine, California, 92697

  • United Health Services Hospitals

    Johnson City, New York, 13903

  • Barnum Medical Research, Inc. 1029 Keyser Ave Suite H

    Natchitoches, Louisiana, 71457

  • Abrazo Health

    Phoenix, Arizona, 85015

  • Beaumont Health

    Royal Oak, Michigan, 48073

  • WellSpan Health

    York, Pennsylvania, 17403

Other trials in United States

Brazil6 sites

  • Hospital Municipal de Barueri Dr. Francisco Moran

    Barueri, São Paulo

  • Hospital Vera Cruz

    Belo Horizonte, Minas Gerais

  • Hospital e Maternidade Celso Pierro - PUCCAMP

    Campinas, São Paulo

  • Santa Casa de Porto Alegre

    Porto Alegre, Rio Grande do Sul

  • Hospital de Base Da Faculdade de Medicina de São José Do Rio Preto

    São José do Rio Preto, São Paulo

  • Avenida Dr. Enéas de Carvalho Aguiar, 44 - Centro de Pesquisa Clínica Prof. Dr. Fúlvio Pileggi - Bloco 1 - 1º Andar

    São Paulo, 103.034

Other trials in Brazil

France6 sites

  • Centre Hospitalier Argenteuil

    Argenteuil

  • Centre Hospitalier Universitaire Bordeaux

    Bordeaux

  • Centre Hospitalier Rene Dubos

    Cergy-Pontoise

  • Centre Hospitalier Départemental de Vendée

    La Roche-sur-Yon

  • Unité ambulatoire Service de Pneumologie, Médecine Intensive et Réanimation (SPMIR) 47-83 Boulevard de l'Hôpital

    Paris, Paris Cedex 13, 75651

  • Hôpital Pitié-Salpêtrière, 47 bd de l'Hôpital, 75013 Paris

    Paris, 75013

Other trials in France

Belgium3 sites

  • CHU Saint-Pierre

    Brussels

  • AZ-Sint Maarten

    Mechelen, 2800

  • CHU CLU Namur (Saint-Elisabeth) Place Louise Godin

    Namur, 15 5000

Other trials in Belgium

Puerto Rico1 site

  • FDI Clinical Research - San Juan City Hospital

    San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: Adaptive Design, Phase 2-3, Randomized, Double-blind, Multicenter Study, Evaluating Safety, Efficacy, PK-PD of BIO101 in Prevention of Respiratory Deterioration in Hospitalized Patients With COVID-19 Pneumonia (Severe)

The COVA clinical study is a global multicentric, double-blind, placebo-controlled, group sequential and adaptive 2 parts phase 2-3 study targeting 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 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).

Read the 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 participants, 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 participants)
Conditions
Covid-19, SARS-CoV2
Being tested
BIO101, Placebo
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BIO101Drug

    Also called Sarconeos (BIO101)

    BIO101 capsules

  • PlaceboDrug

    Also called Sarconeos (placebo)

    placebo capsules

Study groups in NCT04472728
Study groupRoleWhat they receive
BIO101ExperimentalBIO101 350 mg twice daily (BID)
Receives: Drug: BIO101
PlaceboPlacebo comparatorPlacebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Experiencing Negative Events

    Negative events were defined as: all-cause mortality, respiratory failure requiring mechanical ventilation (including cases that were not intubated due to resource restrictions and triage), respiratory failure requiring extracorporeal membrane oxygenation (ECMO), and respiratory failure requiring high-flow oxygen (HFO2). Only the first occurrence of any negative event up to day 28 was considered for the analysis.

    Measured: Up to 28 days

Secondary outcomes (9)

  1. Number of Participants Experiencing Positive Events

    Positive events were defined as participants being officially discharged from hospital care by the department due to improvement in participant condition (self-discharge by participant was not considered a positive event).

    Measured: Up to 28 days

  2. Change From Baseline in Saturation by Pulse Oximetry (SpO2)/Fraction of Inspired Oxygen (FiO2) Ratio

    SpO2/fraction of inspired oxygen (FiO2).

    Oxygen saturation in arterial blood, measured by pulse-oximetry (SpO2). Peripheral arterial oxygen saturation (SpO2) estimates the amount of oxygen in the blood, expressing the percentage of oxygenated hemoglobin compared to the total amount of hemoglobin It will be measured by pulse oximetry, an indirect and non-invasive method.

    The FiO2 and the oxygen delivery system (e.g., simple facial mask; partial rebreather mask; nasal cannula; C-PAP machine) are to be recorded. If FiO2 cannot be read directly from the device, the volume (in liters) and % of oxygen the system delivers (e.g., 100%) should be recorded instead.

    Ratio between SpO2 and FiO2 is calculated

    Measured: Day 3, Day 7, Day 14, and Day 28

  3. Change From Baseline in Oxygen Saturation in Arterial Blood as Measured by SpO2

    Oxygen saturation in arterial blood, measured by pulse-oximetry (SpO2). Peripheral arterial oxygen saturation (SpO2) estimates the amount of oxygen in the blood, expressing the percentage of oxygenated hemoglobin compared to the total amount of hemoglobin It will be measured by pulse oximetry, an indirect and non-invasive method.

    Measured: Day 3, Day 7, Day 14, and Day 28

  4. Number of Participants Experiencing All-cause Mortality

    All-cause mortality refers to the overall death rate in a population, irrespective of the specific reasons for the deaths, covering mortality from all possible causes.

    Measured: Up to 90 days

  5. Time to Reach a Negative Event

    Negative events were defined as: all-cause mortality, respiratory failure requiring mechanical ventilation (including cases that were not intubated due to resource restrictions and triage), respiratory failure requiring ECMO, and respiratory HFO2. Only the first occurrence of any event up to day 28 was considered for the analysis. Median and 95% CI estimates of survival time were based on the Kaplan-Meier analysis.

    Measured: Up to 28 days

  6. Time to Reach a Positive Event

    Positive events were defined as the participants being officially discharged from hospital care by the department due to improvement in participant condition (self-discharge by participant was not considered a positive event).

    Measured: Up to 28 days

  7. Change From Baseline in National Early Warning Score 2 (NEWS2)

    The NEWS2 is based on a simple aggregating scoring system in which scores allocated to physiological measurements (e.g., respiratory rate, oxygen saturation, systolic blood pressure, heart rate, level of consciousness, and temperature) are added up together to provide the clinical status of a patient.

    The total score of NEWS2 is interpreted as follows:

    • 0 to 4: Low risk - Usually indicates the participant is stable, with no immediate cause for concern.
    • 5 to 6: Medium risk - Suggests the participant may require closer monitoring and further assessment.
    • 7 to 20: High risk - Indicates the participant is at significant risk of clinical deterioration and may require urgent medical intervention, including escalation of care to a higher level or immediate medical review.

    Measured: Day 3, Day 7, Day 14, and Day 28

  8. Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

    An AE is any untoward medical occurrence associated with the use of a study medication in humans, whether or not considered study-medication-related. A TEAE was defined as an AE that occurred or worsened in the period from the first dose of study treatment to 30 days after the last dose of the IP. An AE was considered serious if it resulted in any of the following outcomes: death, life-threatening, caused inpatient hospitalization or prolonged existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital abnormality/birth defect, or was an important medical event. AE severity was rated according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death).

    Measured: Up to 90 days

  9. Number of Participants Experiencing TEAEs of Special Interest (EOI)

    The TEAE of special interest in this study included documented events of orthostatic hypotension (OHT) with supine and standing blood pressure measurements, where OHT is defined as a drop in blood pressure from supine to standing position:

    • of ≥20 mmHg in systolic blood pressure (SBP), and/or
    • of ≥10 mmHg in diastolic blood pressure (DBP).

    Measured: Up to 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jul 2020
  2. Study start26 Aug 2020
  3. Primary completion6 Jun 2022
  4. Study completion6 Jun 2022

Why it stopped: Lack of eligible patients due to lower number of Covid-19 cases in all involved sites.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
238 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04472728
Sponsor's protocol ID
BIO101-CL05
Acronym
COVA
Status last verified
Aug 2026
First submitted
6 Jul 2020
Last updated
12 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lobo SM, Plantefeve G, Nair G, Joaquim Cavalcante A, Franzin de Moraes N, Nunes E, Barnum O, Berdun Stadnik CM, Lima MP, Lins M, Hajjar LA, Lipinski C, Islam S, Ramos F, Simon T, Martinot JB, Guimard T, Desclaux A, Lioger B, Neuenschwander FC, DeSouza Paolino B, Amin A, Acosta SA, Dilling DF, Cartagena E, Snyder B, Devaud E, Barreto Berselli Marinho AK, Tanni S, Milhomem Beato PM, De Wit S, Selvan V, Gray J, Fernandez R, Pourcher V, Maddox L, Kay R, Azbekyan A, Chabane M, Tourette C, Esmeraldino LE, Dilda PJ, Lafont R, Mariani J, Camelo S, Rabut S, Agus S, Veillet S, Dioh W, van Maanen R, Morelot-Panzini C. Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial. EClinicalMedicine. 2024 Jan 3;68:102383. doi: 10.1016/j.eclinm.2023.102383. eCollection 2024 Feb.

    PubMed 38545090

  • Dioh W, Chabane M, Tourette C, Azbekyan A, Morelot-Panzini C, Hajjar LA, Lins M, Nair GB, Whitehouse T, Mariani J, Latil M, Camelo S, Lafont R, Dilda PJ, Veillet S, Agus S. Testing the efficacy and safety of BIO101, for the prevention of respiratory deterioration, in patients with COVID-19 pneumonia (COVA study): a structured summary of a study protocol for a randomised controlled trial. Trials. 2021 Jan 11;22(1):42. doi: 10.1186/s13063-020-04998-5.

    PubMed 33430924

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing BIO101 in people with Covid-19 and SARS-CoV2, run by Biophytis at 22 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, Brazil, France, Belgium, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Experiencing Negative Events (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04472728, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.

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