COVID-19
Conditions
Keywords
TNF, XPro1595, DN-TNF, cytokine storm, Quellor, Anti-TNF, Anti-TNF therapy, TNF inhibitor, INB03
Brief summary
The purpose of this study is to determine whether XPro1595 can prevent the progression of respiratory complications in COVID19 patients.
Detailed description
The trial is a Phase 2, double-blind, randomized, placebo-controlled clinical trial of INB03 in participants with pulmonary complications due to COVID-19 infection. Patients with COVID-19 infection and low blood oxygen levels with at least one high risk factor (see below) are eligible to participate in a 40-day study to determine whether INB03 can prevent the progression of pulmonary complications. Eligible participants will be randomized (1:1) to receive either INB03 + standard of care (SOC) or Placebo + SOC. Participants randomized to INB03 + SOC will receive a 1mg/kg injection of INB03 after randomization. Patients that remain in the hospital 7 days after the first dose will receive a second dose. A final safety visit will occur on Day 70.
Interventions
DRUGINB03
Patients will receive up to two once per week subcutaneous injections of 1mg/kg INB03
DRUGPlacebo
Patients will receive up to two once per week subcutaneous injections of Placebo
Sponsors
Inmune Bio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Placebo + Standard of Care vs. INB03 + Standard of Care
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have one or more of the following comorbidities: 1. Age ≥ 65 years; 2. Obesity (BMI ≥ 30); 3. Hypertension (on one or more drugs for treatment of hypertension); 4. Diabetes (on one or more drugs for Type I or Type II diabetes); 5. Cardiovascular disease (on one or more drugs for treatment of cardiovascular disease, other than aspirin); 6. History of congestive heart failure (CHF) or myocardial infarction (MI); 7. Black or African-American race (at least one parent identifies as Black or African-American); 8. Hispanic or Latino ethnicity. 2. Have a positive COVID-19 test in the last 28 days; 3. Have room air SaO2 \< 96%, or SpO2 \< 96% on room air at sea level, or PaO2/FiO2 \< 300; 4. Have abnormal chest X-ray, MRI or CT scan consistent with pulmonary complications from COVID-19; 5. Provide written informed consent prior to any study related procedures being performed.
Exclusion criteria
Participants will be excluded from the study if 1 or more of the following criteria are applicable at Screening: 1. Age \< 18 years; 2. Require immediate intubation due to advanced respiratory failure - including continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BIPAP); 3. Require immediate admission to an Intensive Care Unit (ICU) for any reason; 4. On therapy with approved TNF inhibitor (eg: infliximab, etanercept, adalimumab, certolizumab pegol, golimumab, thalidomide, etc) in the last 6 months; 5. Being treated with dexamethasone (IV or PO) at a dose of \>15mg per day or solumedrol or equivalent corticosteroid at a dose of \>75mg per day; 6. Taking any medication known to be CCR5 receptor antagonist (eg: leronlimab, aplaviroc, vicriviroc or maraviroc) in the last 6 months; 7. Taking any medication known to inhibit the cytokine pathway (eg: anakinra, tocilizumab, siltuximab, etc) in the last 6 months; 8. Known to be pregnant; 9. Has known HIV, HCV or HBV infection; 10. Has known Mycobacterium tuberculosis infection or evidence of infection on chest X-ray; 11. Significant hepatic disease (ALT/AST\> 4 times the ULN); 12. On therapy for cancer in the last 6 months; 13. On therapy for organ transplant in the last 6 months or on a waiting list for organ transplant, including patients on renal replacement therapy for any reason; 14. Known hypersensitivity to investigational product or its excipients; 15. Participating in an investigational drug or device trial; 16. Congestive heart failure (CHF) or myocardial infarction (MI) diagnosed in the last 2 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cochran-Mantel-Haenszel Analysis of Proportion of Patients With Disease Progression | 28 days | Primary Endpoint: Cochran-Mantel-Haenszel Analysis of Proportion of Patients with Disease Progression (mITT Population) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With All-cause Mortality | Through study completion which could be up to Day 70 | Assessing the effect of INB03 on all-cause mortality in participants with pulmonary complications from COVID-19 infection (mITT Population) |
| Proportion Transferred to ICU Level Care by Day 28 | Randomization to Day 28 | Proportion of participants who transferred to ICU level care by Day 28 (ICU level care is defined as a hospital setting where patient to nurse ratio is \< 4) - mITT population |
| Proportion With New Onset of Neurologic Disease by Day 28 | Randomization to Day 28 | Proportion of participants with a new onset of neurologic disease (requiring medical intervention), including stroke by Day 28 (mITT population) |
| Proportion With Evidence of New CHF or New MI Requiring Medical Intervention by Day 28 | Randomization to Day 28 | Proportion of participants with evidence of new CHF or new MI requiring medical intervention by Day 28 - mITT population |
| Proportion With New Onset Embolus or Thrombus by Day 28 | Randomization to Day 28 | Proportion of participants with a new onset embolus or thrombus by Day 28 - mITT population |
| Proportion Developing a Need for Renal Replacement Therapy by Day 28 | Randomization to Day 28 | Proportion of participants who develop a need for renal replacement therapy (defined as need for any type of dialysis including intermittent or continuous peritoneal or hemodialysis) by Day 28 - mITT population |
| Proportion With an Increase in the WHO Ordinal Scale of Clinical Improvement Score at Any Time During the Study | Through study completion, which could be up to Day 70 | Proportion of participants with an increase in the WHO Ordinal Scale of Clinical Improvement score at any time during the study - mITT population |
| Length of Hospital Stay | Randomization to time of discharge or death, whichever occurs firts | Length of hospital stay defined as the number of days in hospital from time of randomization to time of discharge or death, whichever occurs first, mITT population |
| Change From Baseline in Inflammation Markers Over Time - Troponin I | Baseline to Day 40 | Change from Baseline in COVID-19 Specific Inflammation Markers over time in mITT Population - Troponin I |
| Change From Baseline in Inflammation Markers Over Time - Glomerular Filtration Rate | Baseline to Day 40 | Change from Baseline in COVID-19 Specific Inflammation Markers over time in mITT Population - Glomerular Filtration Rate |
| Change From Baseline in Inflammation Markers Over Time - Ferritin | Baseline to Day 40 | Change from Baseline in COVID-19 Specific Inflammation Markers over time in mITT Population - Ferritin |
| Change From Baseline in Inflammation Markers Over Time - D-Dimer | Baseline to Day 40 | Change from Baseline in COVID-19 Specific Inflammation Markers over time in mITT Population - D-Dimer |
| Change From Baseline in Inflammation Markers Over Time - CRP | Baseline to Day 40 | Change from Baseline in COVID-19 Specific Inflammation Markers over time in mITT Population - C-Reactive Protein |
Countries
United States
Contacts
STUDY_CHAIRRaymond Tesi, MD
Inmune Bio, Inc.
Participant flow
Recruitment details
There were 79 patients enrolled to either INB03 + SOC (n=40) or Placebo + SOC (n=39)
Pre-assignment details
There were no stratification factors and each unblinded pharmacist was provided a randomization schedule unique to the specific site.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized <=50 | 28 Participants |
| Age, Customized >50 to 65 | 30 Participants |
| Age, Customized >65 | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 57 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 39 | 1 / 38 |
| other Total, other adverse events | 4 / 39 | 10 / 38 |
| serious Total, serious adverse events | 8 / 39 | 5 / 38 |
Outcome results
None listed