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

Sponsor
Biophytis (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04472728
Collaborator
(none)
310
Enrollment
23
Locations
2
Arms
26.5
Anticipated Duration (Months)
13.5
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
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)

Study Design

Study Type:
Interventional
Anticipated 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 :
Jun 16, 2020
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Sep 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: BIO101

BIO101 350 mg bid

Drug: BIO101
BIO101 capsules
Other Names:
  • Sarconeos (BIO101)
  • Placebo Comparator: Placebo

    Placebo

    Drug: Placebo
    placebo capsules
    Other Names:
  • Sarconeos (placebo)
  • Outcome Measures

    Primary Outcome Measures

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

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

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

    Secondary Outcome Measures

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

      • SpO2/FiO2

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

      • Inflammatory markers including: IL 6 TNFα D-dimer

    3. Interim analysis; indication of activity of BIO101: Renin Angiotensin System biomarkers [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 events [Up to 28 days]

      • official discharge from hospital care by the department due to improvement in participant condition (self-discharge by participant is not considered a positive event)

    5. Additional secondary endpoints for final analysis: Respiratory function [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/HFO2 in participants entering the study on low flow oxygen)

    6. Additional secondary endpoints for final analysis:proportion of patients who experienced negative events [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; • Proportion of participants with CPAP/BiPAP/HFO2 events, defined as requiring CPAP/BiPAP/HFO2 in participants entering the study on low flow oxygen)

    7. Additional secondary endpoint for final analysis: The National Early Warning Score 2 (NewS2): [28 days]

      National Early Warning Score 2 (NewS2): scores: 0-7

    8. Additional secondary endpoint for final analysis: Population Pharmacokinetics study (pop-PK) [1day]

      Cmax: Peak Plasma concentration

    9. Additional secondary endpoint : Population Pharmacokinetics study (pop-PK) [1 day]

      tmax: Time to reach peak plasma concentration

    10. Additional secondary endpoint: Population Pharmacokinetics study (pop-PK) [1 day]

      AUC: Area under the plasma concentration versus time curve

    11. Additional secondary endpoint: Proportion of participants with events of all-cause mortality [Up to 28 days]

      Proportion of participants with events of all-cause mortality

    12. Additional secondary endpoint: time to event: negative events [Up to 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

    13. Additional secondary endpoint: time to event: positive events [Up to 28 days]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    45 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Age: 45 and older (in France: 55 and older)

    2. 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.

    3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration >=3 days

    1. Patients can be included even if treated with: oxygen supplementation, High-flow oxygen (HFO2), BiPAP and CPAP
    1. With evidence of pneumonia based on all of the following:

    2. Clinical findings on a physical examination

    3. Respiratory symptoms developed within the past 14 days

    4. 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:

    5. Tachypnea: ≥25 breaths per minute

    6. Arterial oxygen saturation ≤92%

    7. 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

    8. Without a significant deterioration in liver function tests:

    9. ALT and AST ≤ 5x upper limit of normal (ULN)

    10. Gamma-glutamyl transferase (GGT) ≤ 5x ULN

    11. Total bilirubin ≤ 5×ULN

    12. Willing to participate and able to sign an informed consent form (ICF)

    13. 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.

    3. 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.

    4. 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;

    5. 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)

    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:

    1. 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)
    1. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101

    2. In France:

    • Non-affiliation to compulsory French social security scheme (beneficiary or right-holder)

    • Being under tutelage or legal guardianship

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Abrazo HealthPhoenixArizonaUnited States85015
    2University of California, IrvineIrvineCaliforniaUnited States92697
    3Barnum Medical Research, Inc. 1029 Keyser Ave Suite HNatchitochesLouisianaUnited States71457
    4Beaumont HealthRoyal OakMichiganUnited States48073
    5United Health Services HospitalsJohnson CityNew YorkUnited States13903
    6WellSpan HealthYorkPennsylvaniaUnited States17403
    7CHU Saint-PierreBrusselsBelgium
    8CHU Saint-PierreBrusselBelgium
    9AZ-Sint MaartenMechelenBelgium2800
    10CHU CLU Namur (Saint-Elisabeth) Place Louise GodinNamurBelgium15 5000
    11Hospital Vera CruzBelo HorizonteMinas GeraisBrazil
    12Santa Casa de Porto AlegrePorto AlegreRio Grande Do SulBrazil
    13Hospital Municipal de Barueri Dr. Francisco MoranBarueriSão PauloBrazil
    14Hospital e Maternidade Celso Pierro - PUCCAMPCampinasSão PauloBrazil
    15Hospital de Base Da Faculdade de Medicina de São José Do Rio PretoSão José Do Rio PretoSão PauloBrazil
    16Avenida Dr. Enéas de Carvalho Aguiar, 44 - Centro de Pesquisa Clínica Prof. Dr. Fúlvio Pileggi - Bloco 1 - 1º AndarSão PauloBrazil103.034
    17Unité ambulatoire Service de Pneumologie, Médecine Intensive et Réanimation (SPMIR) 47-83 Boulevard de l'HôpitalParisParis Cedex 13France75651
    18Centre Hospitalier ArgenteuilArgenteuilFrance
    19Centre Hospitalier Universitaire BordeauxBordeauxFrance
    20Centre Hospitalier Rene DubosCergy-PontoiseFrance
    21Centre Hospitalier Départemental de VendéeLa Roche-sur-YonFrance
    22Hôpital Pitié-Salpêtrière, 47 bd de l'Hôpital, 75013 ParisParisFrance75013
    23FDI Clinical Research - San Juan City HospitalSan JuanPuerto Rico00927

    Sponsors and Collaborators

    • Biophytis

    Investigators

    • Principal Investigator: Capucine Morelot-Panzini, MD, Département R3S GHU APHP-Sorbonne Université, Pitié Salpetrière

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Biophytis
    ClinicalTrials.gov Identifier:
    NCT04472728
    Other Study ID Numbers:
    • BIO101-CL05
    First Posted:
    Jul 15, 2020
    Last Update Posted:
    Apr 8, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 8, 2022