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

NCT ID: NCT04472728

Last Updated: 2023-05-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 238 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-26
• Study Completion Date: 2022-09-30

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).

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)

Conditions

Covid-19; SARS-CoV2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

BIO101

BIO101 350 mg bid

Group Type: EXPERIMENTAL

BIO101

Intervention Type: DRUG

BIO101 capsules

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo capsules

Interventions

BIO101

BIO101 capsules

Intervention Type: DRUG

Placebo

placebo capsules

Intervention Type: DRUG

Other Intervention Names

Sarconeos (BIO101); Sarconeos (placebo)

Eligibility Criteria

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

a. Patients can be included even if treated with: oxygen supplementation, High-flow oxygen (HFO2), BiPAP and CPAP

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 14 days

5. 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:

1. Tachypnea: ≥25 breaths per minute

2. Arterial oxygen saturation ≤92%

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)

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

8. In France:

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

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biophytis

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Capucine Morelot-Panzini, MD

Role: PRINCIPAL_INVESTIGATOR

Département R3S GHU APHP-Sorbonne Université, Pitié Salpetrière

Locations

Abrazo Health

Phoenix, Arizona, United States

University of California, Irvine

Irvine, California, United States

Barnum Medical Research, Inc. 1029 Keyser Ave Suite H

Natchitoches, Louisiana, United States

Beaumont Health

Royal Oak, Michigan, United States

United Health Services Hospitals

Johnson City, New York, United States

WellSpan Health

York, Pennsylvania, United States

CHU Saint-Pierre

Brussels, , Belgium

AZ-Sint Maarten

Mechelen, , Belgium

CHU CLU Namur (Saint-Elisabeth) Place Louise Godin

Namur, , Belgium

Hospital Vera Cruz

Belo Horizonte, Minas Gerais, Brazil

Santa Casa de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Municipal de Barueri Dr. Francisco Moran

Barueri, São Paulo, Brazil

Hospital e Maternidade Celso Pierro - PUCCAMP

Campinas, São Paulo, Brazil

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

São José do Rio Preto, São Paulo, Brazil

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

São Paulo, , Brazil

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

Paris, Paris Cedex 13, France

Centre Hospitalier Argenteuil

Argenteuil, , France

Centre Hospitalier Universitaire Bordeaux

Bordeaux, , France

Centre Hospitalier Rene Dubos

Cergy-Pontoise, , France

Centre Hospitalier Départemental de Vendée

La Roche-sur-Yon, , France

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

Paris, , France

FDI Clinical Research - San Juan City Hospital

San Juan, , Puerto Rico

Countries

United States; Belgium; Brazil; France; Puerto Rico

References

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.

Reference Type: DERIVED

PMID: 38545090 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33430924 (View on PubMed)

Other Identifiers

BIO101-CL05

Identifier Type: -

Identifier Source: org_study_id