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

NCT04472728 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: BIO101-CL05
• Study Type: interventional
• Target: 238
• Locations: 5 countries
• Sites: 22

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).

Conditions

Covid-19; SARS-CoV2

Outcome Measures

Primary Outcomes (3)

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

  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

  up to 28 days

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

  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

  up to 28 days

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

  • 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

  up to 28 days

Secondary Outcomes (13)

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

  28 days

• Interim analysis; indication of activity of BIO101: Inflammatory markers

  28 days

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

  28 days

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

  Up to 28 days

• Additional secondary endpoints for final analysis: Respiratory function

  28 days

Study Arms (2)

BIO101

EXPERIMENTAL

BIO101 350 mg bid

Drug: BIO101

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

BIO101 DRUG

BIO101 capsules

Also known as: Sarconeos (BIO101)

BIO101

Placebo DRUG

placebo capsules

Also known as: Sarconeos (placebo)

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• Patient on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO)
• 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
• Patient not able to take medications by mouth (as capsules or as a powder, mixed in water).
• 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)
• 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

Sponsors & Collaborators

• Biophytis: lead

Study Sites (22)

Abrazo Health

Phoenix, Arizona, 85015, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

Barnum Medical Research, Inc. 1029 Keyser Ave Suite H

Natchitoches, Louisiana, 71457, United States

Location

Beaumont Health

Royal Oak, Michigan, 48073, United States

Location

United Health Services Hospitals

Johnson City, New York, 13903, United States

Location

WellSpan Health

York, Pennsylvania, 17403, United States

Location

CHU Saint-Pierre

Brussels, Belgium

Location

AZ-Sint Maarten

Mechelen, 2800, Belgium

Location

CHU CLU Namur (Saint-Elisabeth) Place Louise Godin

Namur, 15 5000, Belgium

Location

Hospital Vera Cruz

Belo Horizonte, Minas Gerais, Brazil

Location

Santa Casa de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Location

Hospital Municipal de Barueri Dr. Francisco Moran

Barueri, São Paulo, Brazil

Location

Hospital e Maternidade Celso Pierro - PUCCAMP

Campinas, São Paulo, Brazil

Location

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

São José do Rio Preto, São Paulo, Brazil

Location

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

São Paulo, 103.034, Brazil

Location

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

Paris, Paris Cedex 13, 75651, France

Location

Centre Hospitalier Argenteuil

Argenteuil, France

Location

Centre Hospitalier Universitaire Bordeaux

Bordeaux, France

Location

Centre Hospitalier Rene Dubos

Cergy-Pontoise, France

Location

Centre Hospitalier Départemental de Vendée

La Roche-sur-Yon, France

Location

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

Paris, 75013, France

Location

FDI Clinical Research - San Juan City Hospital

San Juan, 00927, Puerto Rico

Location

Related Publications (2)

• 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.

  PMID: 38545090 DERIVED

• 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.

  PMID: 33430924 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Capucine Morelot-Panzini, MD

  Département R3S GHU APHP-Sorbonne Université, Pitié Salpetrière

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 15, 2020
• Study Start: August 26, 2020
• Primary Completion: June 6, 2022
• Study Completion: September 30, 2022
• Last Updated: May 15, 2023

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); BR (6); US (6); BE (3); FR (6)