A Phase 2 Study to Evaluate Axatilimab for Hospitalized Participants With Respiratory Involvement Secondary to COVID-19

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Axatilimab for the Treatment of Hospitalized Patients With Respiratory Signs and Symptoms Secondary to Novel Coronavirus Disease (COVID-19)

Conditions
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Coronavirus, COVID, ARDS, Cytokine Storm, Cytokine Release Syndrome

Intervention / Treatment
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* Drug: SNDX-6352
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type of Participant and Disease Characteristics - 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 Hospitalized for COVID-19 Illness of any duration with at least 1 of the following: Clinical assessment (evidence of rales/crackles on exam) and peripheral capillary oxygen saturation less than or equal to 94% on room air, or Requiring mechanical ventilation and/or supplemental oxygen, or 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 If the participant was intubated, must have been intubated less than 24 hours prior to randomization Sex and Contraception Guidelines - 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 - 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 - Active bacterial pneumonia defined: based on either lobar consolidation on x-ray, positive sputum cultures, or leukocytosis with a left shift Known active tuberculosis Participants with acquired immune deficiency syndrome It is not in the best interest of the participants to participate, in the opinion of the treating Investigator. In the opinion of the investigator, progression to death was imminent and inevitable within the next 24 hours, irrespective of the provision of treatments. 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 - 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) Treatment with convalescent plasma Treatment with high doses of corticosteroids (greater than 20 milligrams daily, prednisone equivalent) prior to randomization 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 Previous exposure to study intervention or any other agent targeting colony stimulating factor-1 or CSF-1R or known allergy/sensitivity to study intervention

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Axatilimab (SNDX-6352)<br>Axatilimab on Days 1 and 15, IV + SOC | Drug: SNDX-6352<br>* SNDX-6352<br>* Other names: Axatilimab;|
| Placebo Comparator: Placebo<br>Matching placebo on Days 1 and 15, IV + SOC | Drug: Placebo<br>* Placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 29 | 
| Time To Clinical Improvement | The time to clinical improvement is defined as a national early warning score of ≤2 maintained for 24 hours. | Baseline through Day29 | 
| 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. | Baseline, Day 29 | 
| 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. | Baseline, Day 15 | 
| 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. | Baseline through Day 29 | 
| Count Of Participants Requiring Ventilation Support | Participants who required initiation of mechanical ventilation after study entry are analyzed. | Baseline through Day 29 | 
| 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. | Day 15 | 
| Pharmacokinetics: Serum Concentration Of Axatilimab And Anti-drug Antibodies | The serum concentration of axatilimab and presence of anti-drug antibodies is evaluated. | Day 29 |