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.
Overview
- Phase
- Phase 2
- Intervention
- ABX464
- Conditions
- COVID-19
- Sponsor
- Abivax S.A.
- Enrollment
- 509
- Locations
- 30
- Primary Endpoint
- 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.
- Status
- Terminated
- Last Updated
- 5 months ago
Overview
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.
Investigators
Eligibility Criteria
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
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.
Arms & Interventions
ABX464
ABX464 - Capsules + Standard of Care (SOC)
Intervention: ABX464
Placebo
Placebo - Capsules + Standard of Care (SOC)
Intervention: Placebo
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.
Time Frame: 28 days
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.
Secondary Outcomes
- Rate of Patients Hospitalized(28 days)
- Percentage of Patients Reporting Each Severity Rating on a 7-point Ordinal Scale(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(at each study visit during the 28-day treatment period)
- Number and Rates of Participants With Treatment Emergent Adverse Event(From D0 to D48 (28 days treatment period + up to 20 days Safety follow-up period))