Clinical trial NCT04347226: Anti-Interleukin-8 (Anti-IL-8) for Patients With COVID-19
Official title: A Randomized Phase 2 Study of Anti-IL-8 Therapy Versus Standard of Care in the Treatment of Hospitalized Patients With Severe COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Solid Tumor
Sars-CoV2
Hematological Malignancy
Keywords: COVID-19
coronavirus
corona virus
COVID
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2020-04-15
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to Improvement in the 7-point Ordinal Scale
timeFrame: Up to 10.5 months
Secondary outcomes:
measure: Time to Death
timeFrame: Up to 10.5 months
measure: Time to Intubation
timeFrame: Up to 10.5 months
measure: Proportion of Patients Requiring ICU Admission
timeFrame: Up to 10.5 months
measure: Mortality at 1 Month
timeFrame: 1 month
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Mark N Stein, MD
role: PRINCIPAL_INVESTIGATOR
References: