Clinical trial NCT04415073: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Coronavirus
COVID
ARDS
Cytokine Storm
Cytokine Release Syndrome
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-06-04
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Count Of Participants Alive And Free Of Respiratory Failure At Day 29
timeFrame: Day 29
Secondary outcomes:
measure: Count Of Participants With Secondary Clinical Improvement Outcomes At Day 29
timeFrame: Day 29
measure: Time To Clinical Improvement
timeFrame: Baseline through Day29
measure: Change From Baseline At Day 29 In Oxygenation In Hospitalized Adults With Respiratory Signs And Symptoms Secondary To COVID-19 Treated With Axatilimab
timeFrame: Baseline, Day 29
measure: Change From Baseline At Day 15 In Biomarkers Following Treatment With Axatilimab
timeFrame: Baseline, Day 15
measure: Count Of Participants Experiencing Adverse Events And Serious Adverse Events
timeFrame: Baseline through Day 29
measure: Count Of Participants Requiring Ventilation Support
timeFrame: Baseline through Day 29
measure: Count Of Participants Considered Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Free By Day 15
timeFrame: Day 15
measure: Pharmacokinetics: Serum Concentration Of Axatilimab And Anti-drug Antibodies
timeFrame: Day 29
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
References:
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.