Coronavirus, COVID, ARDS, Cytokine Storm, Cytokine Release Syndrome
Conditions
Brief summary
This was a randomized, double-blind, placebo-controlled, 29-day study to assess the efficacy and safety of axatilimab plus standard of care (SOC), compared with placebo plus SOC, in participants with respiratory signs and symptoms secondary to COVID-19.
Detailed description
Axatilimab (SNDX-6352) is a humanized immunoglobin G4 monoclonal antibody with high affinity against colony stimulating factor-1 receptor (CSF-1R) under investigation for the prevention or treatment of respiratory signs and symptoms secondary to COVID-19. This was a Phase 2, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy, safety and tolerability of axatilimab as an add-on to SOC therapy in hospitalized participants with respiratory signs and symptoms secondary to COVID-19 compared to SOC treatment. Eligible participants were to be randomized in a 1:1 ratio to 1 of 2 treatment groups, active or control. All participants were to receive axatilimab or matching placebo intravenously (IV) as an add-on to SOC on Day 1, within 8 hours of randomization and on Day 15. Participants were to be followed for at least 28 days (+3 days) after the first dose of study intervention (Day 29). The primary objective of the study was to assess the proportion of participants alive and free of respiratory failure at Day 29.
Interventions
DRUGSNDX-6352
SNDX-6352
DRUGPlacebo
Placebo comparator
Sponsors
Syndax Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Type of Participant and Disease Characteristics - 1. Documented or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by an FDA-approved polymerase chain reaction test of nasopharyngeal swab or stool less than 72 hours before randomization 2. Hospitalized for COVID-19 3. Illness of any duration with at least 1 of the following: 1. Clinical assessment (evidence of rales/crackles on exam) and peripheral capillary oxygen saturation less than or equal to 94% on room air, or 2. Requiring mechanical ventilation and/or supplemental oxygen, or 3. Radiographic evidence (chest x-ray or computed tomography scan) of 1 of the following: * Ground-glass opacities, or * Local or bilateral patchy infiltrates, or * Interstitial pulmonary infiltrates 4. If the participant was intubated, must have been intubated less than 24 hours prior to randomization Sex and Contraception Guidelines - 5. Contraceptive use by men or women should have been consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Informed Consent - 6. Capable of giving signed informed consent or by a designated representative, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol
Exclusion criteria
Medical Conditions - 1. Active bacterial pneumonia defined: based on either lobar consolidation on x-ray, positive sputum cultures, or leukocytosis with a left shift 2. Known active tuberculosis 3. Participants with acquired immune deficiency syndrome 4. It is not in the best interest of the participants to participate, in the opinion of the treating Investigator. 5. In the opinion of the investigator, progression to death was imminent and inevitable within the next 24 hours, irrespective of the provision of treatments. 6. Female participants who were pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 90 days after the last dose of study intervention Excluded Prior/Concomitant Therapy - 7. Prior treatment with other agents with actual or possible direct acting anti-inflammatory activity against SARS-CoV-2 in the past 30 days (for example, chloroquine, hydroxychloroquine) 8. Treatment with convalescent plasma 9. Treatment with high doses of corticosteroids (greater than 20 milligrams daily, prednisone equivalent) prior to randomization 10. Treatment with immunomodulators including anti-interleukin (IL)-6, anti-IL-6 receptor antagonists, or with Janus kinase inhibitors in the past 30 days or plans to receive during the study period 11. Previous exposure to study intervention or any other agent targeting colony stimulating factor-1 or CSF-1R or known allergy/sensitivity to study intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count Of Participants Alive And Free Of Respiratory Failure At Day 29 | Day 29 | Respiratory failure was defined by need for mechanical ventilation, extracorporeal membrane oxygenation, non-invasive ventilation \>6 liters oxygen/minute, or clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making was driven solely by resource limitation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count Of Participants With Secondary Clinical Improvement Outcomes At Day 29 | Day 29 | Participants achieving a ≥2 category improvement on a 7-point ordinal score relative to the baseline on Day 28 as collected on Day 29 are reported. |
| Time To Clinical Improvement | Baseline through Day29 | The time to clinical improvement is defined as a national early warning score of ≤2 maintained for 24 hours. |
| Change From Baseline At Day 15 In Biomarkers Following Treatment With Axatilimab | Baseline, Day 15 | The change from baseline at Day 15 in serum concentrations of interleukin 6 and c-reactive protein or hospital discharge or death is evaluated. |
| Change From Baseline At Day 29 In Oxygenation In Hospitalized Adults With Respiratory Signs And Symptoms Secondary To COVID-19 Treated With Axatilimab | Baseline, Day 29 | The change from baseline at Day 29 or hospital discharge or death, if sooner, in the ratio of peripheral hemoglobin oxygen saturation to fraction of inspired oxygen is evaluated. |
| Count Of Participants Requiring Ventilation Support | Baseline through Day 29 | Participants who required initiation of mechanical ventilation after study entry are analyzed. |
| Count Of Participants Considered Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Free By Day 15 | Day 15 | This outcome measure evaluates the antiviral effects of axatilimab in hospitalized adults by Day 15 or hospital discharge, whichever was sooner, with recently diagnosed SARS-CoV-2 infection. |
| Pharmacokinetics: Serum Concentration Of Axatilimab And Anti-drug Antibodies | Day 29 | The serum concentration of axatilimab and presence of anti-drug antibodies is evaluated. |
| Count Of Participants Experiencing Adverse Events And Serious Adverse Events | Baseline through Day 29 | This outcome measure evaluates the safety and tolerability of axatilimab within the same population. A summary of all serious adverse events and other adverse events (nonserious) regardless of causality is located in the 'Reported Adverse Events' section. |
Countries
United States
Participant flow
Pre-assignment details
This study was terminated by the Sponsor given enrollment challenges, partly attributable to the constantly changing novel coronavirus disease (COVID-19) treatment landscape. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Participants by arm
| Arm | Count |
|---|---|
| Axatilimab (SNDX-6352) Axatilimab on Days 1 and 15, IV + SOC | 0 |
| Placebo Matching placebo on Days 1 and 15, IV + SOC | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Count Of Participants Alive And Free Of Respiratory Failure At Day 29
Respiratory failure was defined by need for mechanical ventilation, extracorporeal membrane oxygenation, non-invasive ventilation \>6 liters oxygen/minute, or clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making was driven solely by resource limitation.
Time frame: Day 29
Population: This study was terminated by the Sponsor. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Change From Baseline At Day 15 In Biomarkers Following Treatment With Axatilimab
The change from baseline at Day 15 in serum concentrations of interleukin 6 and c-reactive protein or hospital discharge or death is evaluated.
Time frame: Baseline, Day 15
Population: This study was terminated by the Sponsor. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Change From Baseline At Day 29 In Oxygenation In Hospitalized Adults With Respiratory Signs And Symptoms Secondary To COVID-19 Treated With Axatilimab
The change from baseline at Day 29 or hospital discharge or death, if sooner, in the ratio of peripheral hemoglobin oxygen saturation to fraction of inspired oxygen is evaluated.
Time frame: Baseline, Day 29
Population: This study was terminated by the Sponsor. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Count Of Participants Considered Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Free By Day 15
This outcome measure evaluates the antiviral effects of axatilimab in hospitalized adults by Day 15 or hospital discharge, whichever was sooner, with recently diagnosed SARS-CoV-2 infection.
Time frame: Day 15
Population: This study was terminated by the Sponsor. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Count Of Participants Experiencing Adverse Events And Serious Adverse Events
This outcome measure evaluates the safety and tolerability of axatilimab within the same population. A summary of all serious adverse events and other adverse events (nonserious) regardless of causality is located in the 'Reported Adverse Events' section.
Time frame: Baseline through Day 29
Population: This study was terminated by the Sponsor. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Count Of Participants Requiring Ventilation Support
Participants who required initiation of mechanical ventilation after study entry are analyzed.
Time frame: Baseline through Day 29
Population: This study was terminated by the Sponsor. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Count Of Participants With Secondary Clinical Improvement Outcomes At Day 29
Participants achieving a ≥2 category improvement on a 7-point ordinal score relative to the baseline on Day 28 as collected on Day 29 are reported.
Time frame: Day 29
Population: This study was terminated by the Sponsor. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Pharmacokinetics: Serum Concentration Of Axatilimab And Anti-drug Antibodies
The serum concentration of axatilimab and presence of anti-drug antibodies is evaluated.
Time frame: Day 29
Population: This study was terminated by the Sponsor. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.
Secondary
Time To Clinical Improvement
The time to clinical improvement is defined as a national early warning score of ≤2 maintained for 24 hours.
Time frame: Baseline through Day29
Population: This study was terminated by the Sponsor. Due to study termination and only 1 participant being enrolled there are concerns regarding participant confidentiality, therefore no data are being reported.