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

Phase 3TerminatedNCT04393038

Abivax S.A.509 enrolled

Overview

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).

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

509

Conditions

COVID-19

Interventions

ABX464DRUG

ABX464 50mg QD for 28 days + Standard of Care

PlaceboDRUG

Placebo 50mg QD for 28 days + Standard of Care

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (30)

Outcomes

Primary Outcomes

Rate of Responders: i.e. Rate of Patients Who do Not Require Use of High-flow Oxygen Invasive or Non-invasive Mechanical Ventilation (IMV and NIV, Respectively) Within 28 Days and Who Are Alive at the End of the 28 Days Period.

Subjects will be assessed as responders if they did not receive oxygen supplementation through IMV and NIV during the treatment period, and they are alive at the end of the 28-days treatment period. Non responders are subjects who receive oxygen supplementation (through IMV and NIV during the treatment period) and/or who die during the 28-days treatment period. The use of high-flow oxygen being defined as settings of 3 L/min or greater AND with at least one SpO2 measurement \< 92%, with or without O2 supplementation). Descriptive statistics will be presented by treatment arm.

Time frame: 28 days

Secondary Outcomes

Rate of Patients Hospitalized

To evaluate the proportion of patients requiring hospitalization during the study compared to the {Standard of Care + placebo} group An interim analysis was triggered when the first 305 patients were randomized in the study. As the study was stopped for futility based on the interim analysis results, no efficacy data were collected for the patients who were randomized but not included in the interim analysis. Efficacy results are only available for the 305 patients randomized at the time of the interim analysis.

Time frame: 28 days

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 An interim analysis was triggered when the first 305 patients were randomized in the study. As the study was stopped for futility based on the interim analysis results, no efficacy data were collected for the patients who were randomized but not included in the interim analysis. Only key outcome analysis was performed during this interim analysis. After discontinuation of the study for futility, Abivax decided to not perform the analysis on this secondary outcome (SAP was amended accordingly). Therefore, these data are not available.

Data from ClinicalTrials.gov

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