Acute Lung Injury, ARDS, COVID-19 Pneumonia
Conditions
Brief summary
The study is a prospective, randomized, placebo-controlled, double-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT (Lymphotoxin-like, exhibits Inducible expression, and competes with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a receptor expressed by T lymphocytes), for the treatment of patients with 2019 novel coronavirus disease (COVID-19) pneumonia who have mild to moderate Acute Respiratory Distress Syndrome (ARDS). LIGHT is a cytokine in the tumor necrosis factor super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS. The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.
Interventions
DRUGCERC-002
Administered once subcutaneously at 16 mg/kg dose up to a maximum dose of 1200 mg.
DRUGPlacebo
Administered once subcutaneously
Sponsors
Aevi Genomic Medicine, LLC, a Cerecor company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind (Participant, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject/legally authorized representative (LAR) is able to understand and provide written informed consent, and assent (as applicable) to participate in this study. 2. Subject is ≥18 years of age at the time of informed consent and assent (as applicable). 3. Subject is male or non-pregnant, non-lactating female, who if of childbearing potential agrees to comply with any applicable contraceptive requirements if. discharged from the hospital prior to completing the study. 4. Subject has a diagnosis of COVID-19 infection through an approved testing method. 5. Subject has been hospitalized due to clinical diagnosis of pneumonia with acute lung injury defined as diffuse bilateral radiographic infiltrates with partial pressure of arterial oxygen/percentage of inspired oxygen (PaO2/FiO2) \>100 and \<300. 6. Subject's oxygen saturation at rest in ambient air \<93%
Exclusion criteria
1. Subject is intubated. 2. Subject is currently taking immunomodulators or anti-rejection drugs. 3. Subject has been administered an immunomodulating biologic drug within 60 days of baseline. 4. Subject is in septic shock defined as persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP) of 65 mm Hg or higher and a serum lactate level greater than 2 mmol/L (18 mg/dL) despite adequate volume resuscitation. 5. Subject has received any live attenuated vaccine, such as varicella-zoster, oral polio, or rubella, within 3 months prior to the baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Alive and Free of Respiratory Failure | Baseline to Day 28 | Respiratory failure defined based on resource utilization requiring at least one of the following: * Endotracheal intubation and mechanical ventilation * Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates \>20L/min with fraction of delivered oxygen ≥0.5) * Noninvasive positive pressure ventilation, * Extracorporeal membrane oxygenation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Are Alive at Day 28 | Baseline to Day 28 | 1-month mortality defined as the number of subjects who are alive at the Day 28/ET visit |
Countries
United States
Participant flow
Recruitment details
Of the 88 enrolled patients, 83 met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| CERC-002 CERC-002: Administered once subcutaneously at 16 mg/kg dose up to a maximum dose of 1200 mg. | 41 |
| Placebo Placebo: Administered once subcutaneously | 42 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 7 |
| Overall Study | Discharged prior to receiving study treatment | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | CERC-002 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 28 Participants | 11 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants | 31 Participants | 24 Participants |
| Age, Continuous | 58.7 years STANDARD_DEVIATION 14.28 | 58.1 years STANDARD_DEVIATION 14.21 | 59.2 years STANDARD_DEVIATION 14.5 |
| Body Mass Index (BMI) | 33.3 kg/m^2 STANDARD_DEVIATION 7.63 | 32.3 kg/m^2 STANDARD_DEVIATION 6.46 | 34.3 kg/m^2 STANDARD_DEVIATION 8.58 |
| Corticosteroid Use No | 10 Participants | 6 Participants | 4 Participants |
| Corticosteroid Use Yes | 73 Participants | 36 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 10 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants | 31 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 68 Participants | 37 Participants | 31 Participants |
| Region of Enrollment United States | 83 Participants | 42 Participants | 41 Participants |
| Remdesivir Use No | 35 Participants | 15 Participants | 20 Participants |
| Remdesivir Use Yes | 48 Participants | 27 Participants | 21 Participants |
| Sex: Female, Male Female | 26 Participants | 10 Participants | 16 Participants |
| Sex: Female, Male Male | 57 Participants | 32 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 40 | 9 / 42 |
| other Total, other adverse events | 10 / 40 | 6 / 42 |
| serious Total, serious adverse events | 8 / 40 | 12 / 42 |
Outcome results
Primary
Number of Subjects Alive and Free of Respiratory Failure
Respiratory failure defined based on resource utilization requiring at least one of the following: * Endotracheal intubation and mechanical ventilation * Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates \>20L/min with fraction of delivered oxygen ≥0.5) * Noninvasive positive pressure ventilation, * Extracorporeal membrane oxygenation
Time frame: Baseline to Day 28
Population: The number of subjects alive and free of respiratory failure up to Day 28/Early Termination (ET). The study was designed with broad eligibility criteria allowing patients who received high-flow oxygen or positive-pressure oxygen prior to dosing to be enrolled. As overlap was expected patients who were in respiratory failure before dosing or who required elevation in their ventilation support were excluded from the primary analysis (N=20, 9 CERC-002 patients and 11 placebo patients).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CERC-002 | Number of Subjects Alive and Free of Respiratory Failure | 26 Participants |
| Placebo | Number of Subjects Alive and Free of Respiratory Failure | 20 Participants |
Comparison: The sample size provided greater than 80% power to detect a difference of 0.25 in the proportion of subjects alive and free of respiratory failure using a Chi-square exact test at a one-sided significance level of 0.05. This calculation assumed that the proportion alive and free of respiratory failure will be 0.60 in the placebo group and 0.85 in the CERC-002 group.p-value: 0.04490% CI: [1.04, 7.88]Regression, Logistic
Secondary
Number of Subjects Who Are Alive at Day 28
1-month mortality defined as the number of subjects who are alive at the Day 28/ET visit
Time frame: Baseline to Day 28
Population: The Full Analysis Set included all subjects who received at least one dose of investigational product and had a baseline and at least one post-baseline efficacy assessment. There was 1 subject who did not have a survival status at Day 28 so is therefore excluded from the secondary analysis of the number of subjects who were alive at Day 28.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CERC-002 | Number of Subjects Who Are Alive at Day 28 | 36 Participants |
| Placebo | Number of Subjects Who Are Alive at Day 28 | 36 Participants |
Comparison: The proportion of subjects alive at Day 28/ET in the CERC-002 group was compared to that in the placebo group using logistic regression methods. The logistic regression model included terms for treatment group. Model based point estimate (i.e., odds ratio \[OR\]), 90% confidence interval \[CI\], and one-sided p-value were reported.p-value: 0.176290% CI: [0.59, 6.82]Regression, Logistic