Solid Tumor, Sars-CoV2, Hematological Malignancy
Conditions
Keywords
COVID-19, coronavirus, corona virus, COVID
Brief summary
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.
Detailed description
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.
Interventions
DRUGBMS-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).
Sponsors
Bristol-Myers Squibb
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will receive either BMS-986253 2400mg intravenous (IV) at 0 and 2 weeks (if patient is still hospitalized) and then 4 weeks (only if continued severe respiratory disease) or standard of care treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Improvement in the 7-point Ordinal Scale | Up to 10.5 months | The time to improvement in the 7-point ordinal scale in patients treated with anti-IL-8 therapy compared to standard of care/controls. Measured from baseline to 2 point or greater improvement in 7-point ordinal scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Death | Up to 10.5 months | The time to death will be defined as the time from onset from symptoms until death from any cause. Patients who are alive or lost to follow-up at the cut-off date will be censored from this analysis. |
| Time to Intubation | Up to 10.5 months | The time to intubation will be defined as the time from symptom onset until time of intubation. Any patients already intubated at enrollment will be censored from this analysis. |
| Proportion of Patients Requiring ICU Admission | Up to 10.5 months | The proportion of patients requiring intensive care unit (ICU) admission will be calculated as the number of patients requiring ICU admission over the course of their hospitalization over the number of evaluable patients. |
| Mortality at 1 Month | 1 month | Number of participants who have died 1 month from the time of start of treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BMS-986253 BMS-986253 2400mg IV
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). | 29 |
| Standard of Care Treatment Usual treatment of COVID-19 per study physician discretion | 14 |
| Total | 43 |
Baseline characteristics
| Characteristic | BMS-986253 | Total | Standard of Care Treatment |
|---|---|---|---|
| Age, Continuous | 67.2 years STANDARD_DEVIATION 13.1 | 69.1 years STANDARD_DEVIATION 12.6 | 73.0 years STANDARD_DEVIATION 10.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 20 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 23 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 9 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) White | 8 Participants | 12 Participants | 4 Participants |
| Region of Enrollment United States | 29 Participants | 43 Participants | 14 Participants |
| Sex: Female, Male Female | 14 Participants | 25 Participants | 11 Participants |
| Sex: Female, Male Male | 15 Participants | 18 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 29 | 5 / 14 |
| other Total, other adverse events | 20 / 29 | 5 / 14 |
| serious Total, serious adverse events | 11 / 29 | 4 / 14 |
Outcome results
Primary
Time to Improvement in the 7-point Ordinal Scale
The time to improvement in the 7-point ordinal scale in patients treated with anti-IL-8 therapy compared to standard of care/controls. Measured from baseline to 2 point or greater improvement in 7-point ordinal scale.
Time frame: Up to 10.5 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BMS-986253 | Time to Improvement in the 7-point Ordinal Scale | 12 days |
| Standard of Care Treatment | Time to Improvement in the 7-point Ordinal Scale | 6 days |
Secondary
Mortality at 1 Month
Number of participants who have died 1 month from the time of start of treatment
Time frame: 1 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS-986253 | Mortality at 1 Month | 8 Participants |
| Standard of Care Treatment | Mortality at 1 Month | 4 Participants |
Secondary
Proportion of Patients Requiring ICU Admission
The proportion of patients requiring intensive care unit (ICU) admission will be calculated as the number of patients requiring ICU admission over the course of their hospitalization over the number of evaluable patients.
Time frame: Up to 10.5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986253 | Proportion of Patients Requiring ICU Admission | 9 participants |
| Standard of Care Treatment | Proportion of Patients Requiring ICU Admission | 1 participants |
Secondary
Time to Death
The time to death will be defined as the time from onset from symptoms until death from any cause. Patients who are alive or lost to follow-up at the cut-off date will be censored from this analysis.
Time frame: Up to 10.5 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BMS-986253 | Time to Death | 30 days |
| Standard of Care Treatment | Time to Death | NA days |
Secondary
Time to Intubation
The time to intubation will be defined as the time from symptom onset until time of intubation. Any patients already intubated at enrollment will be censored from this analysis.
Time frame: Up to 10.5 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BMS-986253 | Time to Intubation | 11.5 days |
| Standard of Care Treatment | Time to Intubation | 3 days |