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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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COVID-19

Intervention / Treatment
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* Drug: ABX464
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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. Patients with pulse oximetry arterial saturation ≥ 92 % on room air at enrolment. 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: 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). Patients treated with immunosuppressors and/or immunomodulators. Engrafted patients (organ and/or hematopoietic stem cells). Patients with uncontrolled auto-immune disease. Patients with known or suspected active (i.e. not controlled) bacterial, viral (excluding COVID-19) or fungal infections. Patients with preexisting, severe and not controlled organ failure. History or active malignancy requiring chemotherapy or radiation therapy (excluding 2 years disease free survivor patients). Pregnant or breast-feeding women. Illicit drug or alcohol abuse or dependence that may compromise the patient's safety or adherence to the study protocol. Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer. Hypersensitivity to ABX464 and/or its excipients. Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 2/3, randomized, double blind, placebo-controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABX464<br>ABX464 - Capsules + Standard of Care (SOC) | Drug: ABX464<br>* ABX464 50mg QD for 28 days + Standard of Care<br>|
| Placebo Comparator: Placebo<br>Placebo - Capsules + Standard of Care (SOC) | Drug: Placebo<br>* Placebo 50mg QD for 28 days + Standard of Care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients hospitalized |  | 28-day treatment period | 
| 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 | 
| 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 | 
| Rate of patients requiring oxygen supplementation |  | 28-day treatment period | 
| Time to hospitalization |  | 28-day treatment period | 
| Time to assisted ventilation and oxygen supplementation |  | 28-day treatment period | 
| Change from baseline in microRNA-124 levels |  | at each study visit during the 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 | Nasopharyngeal sample and/or in blood | at each study visit during the 28-day treatment period | 
| Number and rates of participants with Treatment Emergent Adverse Event |  | 28-day treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, ABX464