This study is for patients that are hospitalized for Coronavirus Disease 2019 (COVID-19). The purpose of this study is to see whether neutralizing interleukin-8 (IL-8) with BMS-986253 can help improve the health condition of participants infected with COVID-19. This is the first in-human study of this investigational product specifically in patients with severe COVID-19. Currently there are no FDA approved medications that improve the chance of survival in patients diagnosed with COVID-19. However there are usual treatments currently being used to help treat COVID-19 patients and BMS-986253 will be compared to these standard of care treatments in this study.
This is a single center, randomized, open-label, phase 2 trial to evaluate the
time-to-improvement in the 7 point ordinal scale following treatment with anti-IL-8 therapy
(BMS-986253) compared to standard of care in hospitalized patients with COVID-19 respiratory
disease. Patients will be randomized 2:1 to receive either BMS-986253 or standard of care.
Patients randomized to treatment with BMS-986253 will receive between 1-3 doses of therapy
depending on their clinical status. Participants will be assessed daily while in the hospital
and with then be followed for up to 1 year after discharge.
Drug: BMS-986253
BMS-986253 2400mg IV at 0 and 2 weeks (if patient is still hospitalized) and then 4 weeks (only if still hospitalized with continued severe respiratory disease).
Inclusion Criteria
- Male or female adult ≥ 18 years of age at time of enrollment.
- Confirmed diagnosis of 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 and requiring
supplemental oxygen) 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.
- Adequate laboratory tests including:
- absolute neutrophil count (ANC) >500 cells/mm3
- Platelet count >20,000 cells/mm3
- Serum total bilirubin <1.5 × upper limit of normal (ULN)
- alanine aminotransferase (ALT) <5 × ULN
- aspartate aminotransferase (AST) <5 × ULN
- Age and Reproductive Status
1. Males and females, aged at least 18 years old
2. 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.
3. Women must not be breastfeeding.
4. 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.
5. WOCBP who are continuously not heterosexually active are also exempt from
contraceptive requirements, but should still undergo pregnancy testing as
described in this section.
6. 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.
7. 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 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.
o Exception is remdesivir, hydroxychloroquine or other treatments being used as
compassionate use for COVID-19.
- Expected non-COVID-related survival of < 2 months.
- Ongoing systemic immunosuppressive therapy ≤ 14 days prior to study treatment
administration (except for adrenal replacement steroid doses ≤ 10mg daily prednisone
equivalent in the absence of active autoimmune disease or a short course of steroids
(<5 days) up to 7 days prior to initiating study treatment).
- 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 o 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.
Columbia University Irving Medical Center
New York, New York, United States
Matthew Dallos, MD, Principal Investigator
Columbia University