Anti-IL-8 (BMS-986253) for Hospitalized Patients with COVID-19
This phase II trial investigates how well BMS-986253 works in treating hospitalized patients with severe COVID-19. COVID-19 is a highly contagious respiratory disease caused by the SARS-CoV-2 virus. The primary causes of death in patients infected with SARS-CoV-2 is acute respiratory distress syndrome, which is primarily a process mediated by molecules promoting inflammation that in turn leads to profound lung injury. BMS-986253 is a human monoclonal antibody against the inflammation promoting mediator called interleukin-8 (IL-8), with potential antineoplastic activities. BMS-986253 may help to improve the outcome of COVID-19 patients.
Inclusion Criteria
- Confirmed diagnosis of COVID19 infection (SARS-CoV-2 infection) =< 14 days prior to registration
- Inpatient hospitalization (or documentation of a plan to admit to the hospital if the patient is in the emergency department)
- Evidence of pneumonia by chest radiographs, chest CT OR chest auscultation (rales, crackles)
- Severe respiratory disease (oxygen saturation =< 93% on room air or requires >= 2 L oxygen by nasal cannula [NC] in order to maintain oxygen saturation [SaO2] >= 93%) OR critical respiratory disease (requiring non-rebreather, non-mechanical/mechanical ventilation, high-flow nasal cannula, ICU admission)
- Patients can continue their anti-cancer therapy at the discretion of the treating physician
- Absolute neutrophil count (ANC) > 500 cells/mm^3
- Platelet count > 20,000 cells/mm^3
- Serum total bilirubin < 1.5 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) < 5 x ULN
- Aspartate aminotransferase (AST) < 5 x ULN
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study treatment
- Women must not be breastfeeding
- WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment plus for a total of 155 days post treatment completion. Local laws and regulations may require use of alternative and/or additional contraception methods
- WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, but should still undergo pregnancy testing as described in this section
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception during study treatment with BMS-986253 for a total of 215 days post-treatment completion
- Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section
- Willingness to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent). In cases of partial impairment, impairment that fluctuates over time, or complete impairment due to dementia, stroke, traumatic brain injury, developmental disorders (including mentally disabled persons), serious mental illness, delirium, medical sedation, or intubation, a subject may be enrolled if the subject’s legally authorized representative consents on the subject’s behalf
Exclusion Criteria
- Treatment with anti-IL-6, anti-IL-6R antagonists or Janus kinase inhibitor (JAKi) within 48 hours of first dose of study treatment
- No other investigational therapies with the intent to treat the patient’s COVID-19 can be administered while the patient is enrolled in the study. * Exception is remdesivir, hydroxychloroquine or other treatments being used as compassionate use for COVID-19
- Expected non-COVID-related survival of < 2 months
- Receipt of non-oncology vaccines containing live virus for prevention of infectious diseases within 4 weeks prior to first dose of study treatment
- History of severe hypersensitivity reaction to any monoclonal antibody (mAb)
- Multi-organ failure requiring vasopressors or continuous veno-venous hemofiltration (CVVH) or extracorporeal membrane oxygenation
- No active systemic bacterial or fungal infection * Patients with a history of positive bacterial or fungal cultures but on enrollment do not have suspected or known active systemic bacterial or fungal infections are permitted
Additional locations may be listed on ClinicalTrials.gov for NCT04347226.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To determine the time to improvement in the 7-point ordinal scale in patients treated with anti-IL-8 therapy compared to standard of care/controls.
SECONDARY OBJECTIVES:
I. To evaluate the time to death in patients treated with anti-IL-8 therapy compared to controls.
II. To evaluate the mortality 1 month after start of treatment in patients treated with anti-IL-8 therapy compared to controls.
III. To determine the time to intubation in patients treated with anti-IL-8 therapy compared to controls.
IV. To estimate the time to improvement in oxygenation in patients treated with anti-IL-8 therapy compared to controls.
V. To measure the proportion of patients requiring intensive care unit (ICU) admission at 1 month in patients treated with anti-IL-8 therapy compared to controls.
VI. To assess the safety and tolerability defined as adverse events graded by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 in patients treated with anti-IL-8 therapy compared to controls.
VII. To assess the duration of hospitalization in patients treated with anti-IL-8 therapy compared to controls.
VIII. To compare the raw 7-point ordinal scale scores at day 14 in patients treated with anti-IL-8 therapy versus controls.
EXPLORATORY OBJECTIVES:
I. To assess the change in LDH, D-Dimer, CRP, ESR, NLR and absolute lymphocytes before and after treatment and over time (every 2 days for duration of hospitalization).
II. To assess the change in sIL-6 before and after treatment and over time.
III. To evaluate radiological response by comparing percent (%) of lung fields with infiltrates on chest imaging (chest x-ray [CXR] and computed tomography [CT]) through independent radiology review.
IV. To measure time on ventilation measured from time of intubation to time of definitive extubation.
V. To measure time to improvement in National Early Warning Score (NEWS)2 score to =< 2.
VI. To evaluate the change in NEWS2 from baseline.
VII. To measure proportion of patients with multi-organ failure at 1 month.
VIII. To assess whether IL-8 and other key cytokines (tumor necrosis factor [TNF], IL-1b, IL-6) at baseline and during treatment are predictive of treatment efficacy by quantification of circulating IL-1b, IL8, TNFalpha and IL-6 levels over time.
IX. To quantify changes in humoral immune responses by antibody profiling at baseline and following treatment.
X. To characterize pharmacokinetics (PK) of anti-IL-8 monoclonal antibody HuMax-IL8 (BMS-986253) in cancer patients with severe COVID-19.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive anti-IL-8 monoclonal antibody HuMax-IL8 (BMS-986253) intravenously (IV) over 120-180 minutes every 2 weeks for up to 3 doses (on days 1, 15, and 29) in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo standard of care.
After completion of study treatment, patients are followed up for 100 days, and then every 3 months for up to 1 year.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationNYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Principal InvestigatorMatthew Dallos
- Primary IDAAAS9881
- Secondary IDsNCI-2020-05615
- ClinicalTrials.gov IDNCT04347226