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

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.

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.

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.