ABX464 in Treating Inflammation and Preventing Acute Respiratory Failure in Patients With COVID-19

COVID-19 Clinical Trial

— Mir-Age  

Official title:

A Phase 2/3, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and the Safety of ABX464 in Treating Inflammation and Preventing COVID-19 Associated Acute Respiratory Failure in Patients Aged ≥ 65 and Patients Aged ≥18 With at Least One Additional Risk Factor Who Are Infected With SARS-CoV-2.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04393038
• Other study ID #: ABX464-401
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: July 1, 2020
• Est. completion date: April 16, 2021

Study information

• Verified date: June 2021
• Source: Abivax S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase 2/3, randomized, double blind, placebo-controlled study to evaluate the efficacy and the safety of ABX464 in treating inflammation and preventing acute respiratory failure in patients aged ≥65 and patients aged ≥18 with at least one additional risk factor who are infected with SARS-CoV-2 (the MiR-AGE study).

Description:

This phase 2/3 study will evaluate the efficacy and safety of ABX464 50mg QD (oral capsule), on treating inflammation and preventing acute respiratory failure in patients infected with SARS-CoV-2.

Eligible patients will be randomized according to a 2:1 ratio into 2 treatment cohorts as follows:

• Standard of Care + Placebo cohort: 344 patients

• Standard of Care + ABX464 50mg QD: 690 patients

Study design:

The study will consist of 2 periods:

• Treatment phase: randomized patients will be treated for 28 days

• Safety follow-up phase of 14 days after which the End of Study visit (EOS) will be performed.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 509
• Est. completion date: April 16, 2021
• Est. primary completion date: March 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult (= 18 years old) men or women, hospitalized or not hospitalized, diagnosed for SARS-CoV-2 infection by PCR, with at least one associated risk factor. Considered risk factors are:

• Age = 65 years

• Obesity defined as BMI = 30

• Recent history of uncontrolled High Blood Pressure (SBP > 150 mm Hg DBP >100 mm Hg) according to investigator

• Treated diabetes (type I or II)

• History of ischemic cardiovascular disease

2. Symptomatic patients at enrollment. Symptoms are defined as fever (body temperature = 37.8 C oral/tympanic, or = 38.2 C rectal) for more than 24 hours associated either with headache, sore throat, dry cough, fatigue, chest pain or choking sensation (with no associated respiratory distress), myalgia, anosmia or ageusia.

3. Patients with pulse oximetry arterial saturation = 92 % on room air at enrolment.

4. Patients with the following hematological and biochemical laboratory parameters obtained within 7 days prior to Day 0:

• Hemoglobin above 9.0 g / dL

• Absolute Neutrophil Count = 1000 / mm3

• Platelets = 100 000 mm3;

• Creatinine clearance = 50 mL / min by the Cockcroft Gault formula

• Total serum bilirubin < 2 x ULN

• Alkaline phosphatase < 2 x ULN, AST (SGOT) and ALT (SGPT) < 3 x ULN;

Exclusion Criteria:

1. Patients with moderate or severe acute respiratory failure or requiring noninvasive ventilation or oxygen or with SpO2 < 92% or tachypnea (respiratory rate = 30 breaths/min).

2. Patients treated with immunosuppressors and/or immunomodulators.

3. Engrafted patients (organ and/or hematopoietic stem cells).

4. Patients with uncontrolled auto-immune disease.

5. Patients with known or suspected active (i.e. not controlled) bacterial, viral (excluding COVID-19) or fungal infections.

6. Patients with preexisting, severe and not controlled organ failure.

7. History or active malignancy requiring chemotherapy or radiation therapy (excluding 2 years disease free survivor patients).

8. Pregnant or breast-feeding women.

9. Illicit drug or alcohol abuse or dependence that may compromise the patient's safety or adherence to the study protocol.

10. Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer.

11. Hypersensitivity to ABX464 and/or its excipients.

12. Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.

Related Conditions & MeSH terms

• COVID-19
• Inflammation
• Respiratory Insufficiency

Intervention

Drug:
• ABX464
ABX464 50mg QD for 28 days + Standard of Care
• Placebo
Placebo 50mg QD for 28 days + Standard of Care

Locations

Country	Name	City	State
Belgium	Centre hospitalier Saint Pierre	Brussels
Belgium	Hôpital Erasme	Brussels
Belgium	UZ Gent	Gent
Brazil	Centro Oncológico de Roraima - CECOR - NAP	Boa Vista	Roraima
Brazil	Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - Instituto de Pesquisa Clínica Carlos Borborema	Manaus	Amazonas
Brazil	Instituto Nacional de Infectologia Evandro Chagas - FIOCRUZ Rio de Janeiro	Rio De Janeiro
Brazil	Conjunto Hospitalar do Mandaqui	Sao Paulo
Brazil	Hospital das Clinicas da FMUSP	São Paulo	Sao Paulo
France	Hôpital Nord	Amiens
France	Centre Hospitalier Départemental de Vendée	La Roche-sur-Yon
France	Centre Hospitalier Universitaire de Nice	Nice
France	Hôpital Saint-Antoine	Paris
Germany	Universitätsklinikum Bonn	Bonn	Nordrhein-Westfalen
Germany	Asklepios Klinik Altona	Hamburg
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Universitätsmedizin Mannheim Ruprecht-Karls-Universität Heid	Mannheim	Baden-Württemberg
Italy	Ospedale A. Manzonidi Lecco - ASST Lecco	Lecco
Italy	Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico - Infectious Diseases	Milano	Lombardia
Italy	Ospedale Luigi Sacco, AO-PU	Milano	Lombardia
Italy	Ospedale Niguarda	Milano
Italy	Ospedale San Paolo	Milano	Lombardia
Italy	Ospedale di Vittorio Veneto - Medecina generale	Vittorio Veneto	Treviso
Mexico	Consultorio médico	Mérida	Yucatan
Mexico	Centro de Prevención y Rehabilitación de Enfermedades Pulmon	Nuevo León
Spain	H.G.U. Alicante	Alicante
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital de La Princesa	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
United Kingdom	Royal Free Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Abivax S.A.

Countries where clinical trial is conducted

Belgium,  Brazil,  France,  Germany,  Italy,  Mexico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of patients with no invasive or non-invasive mechanical ventilation (IMV and NIV, respectively), but excluding simple nasal/mask oxygen supplementation, and who are alive		at the end of the 28-day treatment period
Secondary	Rate of patients hospitalized		28-day treatment period
Secondary	Percentage of patients reporting each severity rating on a 7-point ordinal scale	7-point ordinal scale is defined as Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death	28-day treatment period
Secondary	Change from enrolment in inflammatory markers in plasma and in immune phenotype and assessment of cell-activation markers in PBMCs		at each study visit during the 28-day treatment period
Secondary	Rate of patients requiring oxygen supplementation		28-day treatment period
Secondary	Time to hospitalization		28-day treatment period
Secondary	Time to assisted ventilation and oxygen supplementation		28-day treatment period
Secondary	Change from baseline in microRNA-124 levels		at each study visit during the 28-day treatment period
Secondary	Change from baseline in CRP, Troponin I & T and D-dimer		at each study visit during the 28-day treatment period
Secondary	SARS-CoV-2 viral load	Nasopharyngeal sample and/or in blood	at each study visit during the 28-day treatment period
Secondary	Number and rates of participants with Treatment Emergent Adverse Event		28-day treatment period