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

Phase 2

Terminated

• Conditions: COVID-19
• Interventions: Drug: Placebo; Drug: ABX464

• Registration Number: NCT04393038
• Lead Sponsor: Abivax S.A.

Brief 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).

Detailed 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.

Study Timeline

• Study First Submitted: 2020-05-18
• Study First Submitted QC: 2020-05-18
• Study First Posted: 2020-05-19
• Study Start: 2020-07-01
• Primary Completion: 2021-03-05
• Study Completion: 2021-04-16
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-28
• Last Update Posted: 2021-06-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 509

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;

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo - Capsules + Standard of Care (SOC)
ABX464	ABX464	ABX464 - Capsules + Standard of Care (SOC)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Rate of patients hospitalized	28-day treatment period
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
Time to hospitalization	28-day treatment period
Percentage of patients reporting each severity rating on a 7-point ordinal scale	28-day treatment period	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
Change from baseline in microRNA-124 levels	at each study visit during the 28-day treatment period
Rate of patients requiring oxygen supplementation	28-day treatment period
Time to assisted ventilation and oxygen supplementation	28-day treatment period
Change from baseline in CRP, Troponin I & T and D-dimer	at each study visit during the 28-day treatment period
SARS-CoV-2 viral load	at each study visit during the 28-day treatment period	Nasopharyngeal sample and/or in blood
Number and rates of participants with Treatment Emergent Adverse Event	28-day treatment period

Trial Locations

Locations (30)

Universitätsmedizin Mannheim Ruprecht-Karls-Universität Heid; 🇩🇪 Mannheim, Baden-Württemberg, Germany

Instituto Nacional de Infectologia Evandro Chagas - FIOCRUZ Rio de Janeiro; 🇧🇷 Rio De Janeiro, Brazil

Hôpital Saint-Antoine; 🇫🇷 Paris, France

Centre hospitalier Saint Pierre; 🇧🇪 Brussels, Belgium

UZ Gent; 🇧🇪 Gent, Belgium

Centro Oncológico de Roraima - CECOR - NAP; 🇧🇷 Boa Vista, Roraima, Brazil

Centro de Prevención y Rehabilitación de Enfermedades Pulmon; 🇲🇽 Nuevo León, Mexico

Fundacao de Medicina Tropical Doutor Heitor Vieira Dourado - Instituto de Pesquisa Clínica Carlos Borborema; 🇧🇷 Manaus, Amazonas, Brazil

Ospedale A. Manzonidi Lecco - ASST Lecco; 🇮🇹 Lecco, Italy

Hôpital Nord; 🇫🇷 Amiens, France

Ospedale San Paolo; 🇮🇹 Milano, Lombardia, Italy

Centre Hospitalier Universitaire de Nice; 🇫🇷 Nice, France

Hospital de La Princesa; 🇪🇸 Madrid, Spain

Conjunto Hospitalar do Mandaqui; 🇧🇷 Sao Paulo, Brazil

Hospital Universitari Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico - Infectious Diseases; 🇮🇹 Milano, Lombardia, Italy

Asklepios Klinik St. Georg; 🇩🇪 Hamburg, Germany

Ospedale di Vittorio Veneto - Medecina generale; 🇮🇹 Vittorio Veneto, Treviso, Italy

Asklepios Klinik Altona; 🇩🇪 Hamburg, Germany

Consultorio médico; 🇲🇽 Mérida, Yucatan, Mexico

H.G.U. Alicante; 🇪🇸 Alicante, Spain

Ospedale Luigi Sacco, AO-PU; 🇮🇹 Milano, Lombardia, Italy

Ospedale Niguarda; 🇮🇹 Milano, Italy

Centre Hospitalier Départemental de Vendée; 🇫🇷 La Roche-sur-Yon, France

Hospital das Clinicas da FMUSP; 🇧🇷 São Paulo, Sao Paulo, Brazil

Royal Free Hospital; 🇬🇧 London, United Kingdom

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Universitario Infanta Leonor; 🇪🇸 Madrid, Spain

Universitätsklinikum Bonn; 🇩🇪 Bonn, Nordrhein-Westfalen, Germany

Hôpital Erasme; 🇧🇪 Brussels, Belgium