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

Primary Purpose

Coronavirus, COVID, ARDS

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

SNDX-6352

Placebo

About this trial

This is an interventional treatment trial for Coronavirus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:
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
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

Sites / Locations

HonorHealth
Montefiore Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Axatilimab (SNDX-6352)

Placebo

Arm Description

Axatilimab on Days 1 and 15, IV + SOC

Matching placebo on Days 1 and 15, IV + SOC

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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 To Clinical Improvement

The time to clinical improvement is defined as a national early warning score of ≤2 maintained for 24 hours.

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.

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.

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.

Count Of Participants Requiring Ventilation Support

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

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

The serum concentration of axatilimab and presence of anti-drug antibodies is evaluated.

Full Information

NCT ID

NCT04415073

First Posted

May 29, 2020

Last Updated

June 29, 2022

Sponsor

Syndax Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04415073

Brief Title

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

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Terminated

Why Stopped

Given enrollment challenges, partly attributable to the constantly changing COVID-19 treatment landscape, the trial has been closed.

Study Start Date

May 30, 2020 (Actual)

Primary Completion Date

July 13, 2020 (Actual)

Study Completion Date

July 13, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Syndax Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Axatilimab (SNDX-6352)

Arm Type

Active Comparator

Arm Description

Axatilimab on Days 1 and 15, IV + SOC

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Matching placebo on Days 1 and 15, IV + SOC

Intervention Type

Drug

Intervention Name(s)

SNDX-6352

Other Intervention Name(s)

Axatilimab

Intervention Description

SNDX-6352

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo comparator

Primary Outcome Measure Information:

Title

Count Of Participants Alive And Free Of Respiratory Failure At Day 29

Description

Time Frame

Day 29

Secondary Outcome Measure Information:

Title

Count Of Participants With Secondary Clinical Improvement Outcomes At Day 29

Description

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

Title

Time To Clinical Improvement

Description

The time to clinical improvement is defined as a national early warning score of ≤2 maintained for 24 hours.

Time Frame

Baseline through Day29

Title

Change From Baseline At Day 29 In Oxygenation In Hospitalized Adults With Respiratory Signs And Symptoms Secondary To COVID-19 Treated With Axatilimab

Description

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

Title

Change From Baseline At Day 15 In Biomarkers Following Treatment With Axatilimab

Description

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

Title

Count Of Participants Experiencing Adverse Events And Serious Adverse Events

Description

Time Frame

Baseline through Day 29

Title

Count Of Participants Requiring Ventilation Support

Description

Participants who required initiation of mechanical ventilation after study entry are analyzed.

Time Frame

Baseline through Day 29

Title

Count Of Participants Considered Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Free By Day 15

Description

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

Title

Pharmacokinetics: Serum Concentration Of Axatilimab And Anti-drug Antibodies

Description

The serum concentration of axatilimab and presence of anti-drug antibodies is evaluated.

Time Frame

Day 29

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

HonorHealth

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85258

Country

United States

Facility Name

Montefiore Medical Center

City

Bronx

State/Province

New York

ZIP/Postal Code

10467

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34473343

Citation

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Results Reference

derived

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

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