COVID-19
Conditions
Keywords
COVID-19, ABX464
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.
Interventions
DRUGABX464
ABX464 50mg QD for 28 days + Standard of Care
DRUGPlacebo
Placebo 50mg QD for 28 days + Standard of Care
Sponsors
Abivax S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Blinded treatment bottles
Intervention model description
Phase 2/3, randomized, double blind, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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 | 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. |
| Rate of Patients Requiring Oxygen Supplementation | 28-day treatment period | 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. |
| Time to Hospitalization | 28-day treatment period | 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. |
| Rate of Patients Hospitalized | 28 days | 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. |
| Change From Baseline in microRNA-124 Levels | at each study visit during the 28-day treatment period | 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. |
| Change From Baseline in CRP, Troponin I & T and D-dimer | at each study visit during the 28-day treatment period | 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. |
| SARS-CoV-2 Viral Load | at each study visit during the 28-day treatment period | Nasopharyngeal sample and/or in blood 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. |
| 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) | Number and rates of participants included in the safety analysis set who had Treatment Emergent Adverse Event |
| Time to Assisted Ventilation and Oxygen Supplementation | 28-day treatment period | 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. |
Countries
Belgium, Brazil, France, Germany, Italy, Mexico, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABX464 ABX464 50 mg once a day (oral capsule) for 28 days + Standard of Care (SOC) | 339 |
| Placebo Placebo 50 mg once a day (oral capsule) + Standard of Care (SOC) | 170 |
| Total | 509 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 2 |
| Overall Study | Death | 6 | 4 |
| Overall Study | End of Study date not collected in the eCRF | 10 | 4 |
| Overall Study | Lost to Follow-up | 5 | 4 |
| Overall Study | Other reasons+ trial site terminated by sponsor + Study terminated by sponsor | 94 | 49 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 24 | 8 |
Baseline characteristics
| Characteristic | ABX464 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 98 Participants | 50 Participants | 148 Participants |
| Age, Categorical Between 18 and 65 years | 240 Participants | 120 Participants | 360 Participants |
| Age, Continuous | 54.9 years STANDARD_DEVIATION 15.36 | 54.4 years STANDARD_DEVIATION 15.05 | 54.7 years STANDARD_DEVIATION 15.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 274 Participants | 130 Participants | 404 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 35 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 5 Participants | 16 Participants |
| Region of Enrollment Belgium | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Brazil | 238 participants | 114 participants | 352 participants |
| Region of Enrollment France | 20 participants | 12 participants | 32 participants |
| Region of Enrollment Germany | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Italy | 20 participants | 11 participants | 31 participants |
| Region of Enrollment Mexico | 8 participants | 7 participants | 15 participants |
| Region of Enrollment Peru | 24 participants | 7 participants | 31 participants |
| Region of Enrollment Spain | 24 participants | 15 participants | 39 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 160 Participants | 84 Participants | 244 Participants |
| Sex: Female, Male Male | 179 Participants | 86 Participants | 265 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 335 | 4 / 170 |
| other Total, other adverse events | 115 / 335 | 27 / 170 |
| serious Total, serious adverse events | 36 / 335 | 20 / 170 |
Outcome results
Primary
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
Population: An interim analysis was triggered when the first 305 patients were randomized in the study. Randomization was not discontinued during the interim analysis. 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ABX464 | 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. | Responder | 169 Participants |
| ABX464 | 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. | Non-responder | 24 Participants |
| ABX464 | 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. | Missing | 10 Participants |
| Placebo | 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. | Responder | 87 Participants |
| Placebo | 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. | Non-responder | 7 Participants |
| Placebo | 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. | Missing | 8 Participants |
Secondary
Change From Baseline in CRP, Troponin I & T and D-dimer
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.
Time frame: at each study visit during the 28-day treatment period
Population: Analysis not done at time of interim analysis. After discontinuation of the study for futility, no further efficacy analysis were done
Secondary
Change From Baseline in microRNA-124 Levels
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.
Time frame: at each study visit during the 28-day treatment period
Population: Analysis not done at time of interim analysis. After discontinuation of the study for futility, no further efficacy analysis were done
Secondary
Change From Enrolment in Inflammatory Markers in Plasma and in Immune Phenotype and Assessment of Cell-activation Markers in PBMCs
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.
Time frame: at each study visit during the 28-day treatment period
Population: Analysis not done at time of interim analysis. After discontinuation of the study for futility, no further efficacy analysis were done
Secondary
Number and Rates of Participants With Treatment Emergent Adverse Event
Number and rates of participants included in the safety analysis set who had Treatment Emergent Adverse Event
Time frame: From D0 to D48 (28 days treatment period + up to 20 days Safety follow-up period)
Population: Analysis of safety was performed on the safety data set consisting in all patients who received at least one dose of ABX464 in the study. A total of 505 patients were included in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ABX464 | Number and Rates of Participants With Treatment Emergent Adverse Event | Period 1: AE onset or worsens before or on Day 28 | 209 Participants |
| ABX464 | Number and Rates of Participants With Treatment Emergent Adverse Event | Period 2: AE onset or worsens after Day 28 | 22 Participants |
| Placebo | Number and Rates of Participants With Treatment Emergent Adverse Event | Period 1: AE onset or worsens before or on Day 28 | 83 Participants |
| Placebo | Number and Rates of Participants With Treatment Emergent Adverse Event | Period 2: AE onset or worsens after Day 28 | 20 Participants |
Secondary
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.
Time frame: 28-day treatment period
Population: Analysis not done at time of interim analysis. After discontinuation of the study for futility, no further efficacy analysis were done
Secondary
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
Population: Number of patients randomized at time of Interim analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ABX464 | Rate of Patients Hospitalized | 23 Participants |
| Placebo | Rate of Patients Hospitalized | 11 Participants |
Secondary
Rate of Patients Requiring Oxygen Supplementation
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.
Time frame: 28-day treatment period
Population: Analysis not done at time of interim analysis. After discontinuation of the study for futility, no further efficacy analysis were done
Secondary
SARS-CoV-2 Viral Load
Nasopharyngeal sample and/or in blood 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.
Time frame: at each study visit during the 28-day treatment period
Population: Analysis not done at time of interim analysis. After discontinuation of the study for futility, no further efficacy analysis were done
Secondary
Time to Assisted Ventilation and Oxygen Supplementation
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.
Time frame: 28-day treatment period
Population: Analysis not done at time of interim analysis. After discontinuation of the study for futility, no further efficacy analysis were done
Secondary
Time to Hospitalization
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.
Time frame: 28-day treatment period
Population: Analysis not done at time of interim analysis. After discontinuation of the study for futility, no further efficacy analysis were done