Inflammation, Myocardial Infarction
Conditions
Brief summary
This study will evaluate the potential benefit of blocking inflammation during a heart attack using an investigational anti-inflammatory medicine called SP16. The study will enroll 10 patients and all 10 patients will receive a standard dose of SP16.
Detailed description
The main hypothesis of this study is that a single subcutaneous administration of SP16 0.2 mg/kg is safe and well tolerated in patients with ST segment elevation myocardial infarction (STEMI) and associated with a reduction in the acute inflammatory response to STEMI, as measured as area-under-the-curve (AUC) for C reactive protein (CRP), the preferred inflammatory marker for cardiovascular risk prognostication. SP16 will be administered subcutaneously as this route has greater ease of administration than intravenous injection. A single dose administration has been selected based upon pre-clinical data and expected clinical use of SP16.
Interventions
DRUGSP16
All patients will receive a single dose of SP16
Sponsors
Virginia Commonwealth University
Serpin Pharma, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
In order to be eligible for this study, patients must meet all the 3 criteria: 1. Presentation to the hospital with acute STEMI defined as chest pain (or equivalent) with an onset within 12 hours and electrocardiogram (ECG) evidence of ST segment elevation (\>1 mm) in 2 or more anatomically contiguous leads that is new or presumably new (for intermittent pain lasting more than 12 hours, the time from the when the pain became severe and constant); 2. Coronary intervention planned and/or completed within 12 hours of symptom onset, and enrollment in the study within 6 hours of angiogram (max 18 hours from symptom onset) 3. Age\>21 years In order to be eligible for this study, patients must meet none of the
Exclusion criteria
. * Inability to give informed consent * Hemodynamic instability as defined as need for inotropic or vasoactive agents, or need for mechanical support devices (including intra-aortic balloon pump) * Pregnancy or breastfeeding * Preexisting congestive heart failure (American Heart Association/American College of Cardiology class C-D, New York Heart Association III-IV) * Preexisting severe left ventricular dysfunction (LVEF\<20%) * Preexisting severe valvular heart disease * Known active infections (acute or chronic) * Recent (\<14 days) or active use of immunosuppressive drugs (including but not limited to high-dose corticosteroids \[\>1 mg/kg of prednisone equivalent\], tumor necrosis factor-alpha blockers, cyclosporine) not including non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids used for intravenous (IV) dye allergy only) * Recent (\<14 days) or active use of anti-inflammatory drugs (not including NSAIDs or corticosteroids used for IV dye allergy only) * Known chronic inflammatory disease (including but not limited to rheumatoid arthritis, systemic lupus erythematosus) * Known active malignancy of any type, or prior diagnosis in the past 10 years * Neutropenia (absolute neutrophil count\<1,800/mm3 \[or \<1,000/mm3 in African American patients\]) * Severe impairment in renal function (estimated glomerular filtration rate \<30 ml/kg\*min) * Anticipated need for cardiac or major surgery * Known Allergy to SP16
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) for C-reactive Protein (CRP) | Baseline, 72 hours, 14 days | This study will evaluate the anti-inflammatory effect of SP16 by calculating the AUC for CRP. This is done by measuring CRP at baseline, 72 hours, and 14 days. The AUC will then be compared to historical controls to evaluate whether or not SP16 reduces the AUC for CRP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Curve (AUC) for Creatine-Kinase Myocardial Band (CK-MB) | 72 hours | This study will estimate the infarct size based upon area under the curve (AUC) for creatine-kinase myocardial band (CK-MB). The AUC calculation will come from CK-MB levels drawn during usual care. The infarct size will then be compared to historical controls to evaluate whether or not SP16 reduces the infarct size. |
| Change in Left Ventricular Ejection Fraction (LVEF) at Baseline and 365 Days | 365 days | Patients will undergo transthoracic echocardiography at baseline and 365 days to evaluate the change in LVEF. |
| Diagnosis of Heart Failure | 365 days | Number of participants diagnosed with heart failure at 1 year follow up |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SP16 Patients will receive a single dose of SP16 0.2 mg/kg by subcutaneous injection
SP16: All patients will receive a single dose of SP16 | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | SP16 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 55 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 6 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Area Under the Curve (AUC) for C-reactive Protein (CRP)
This study will evaluate the anti-inflammatory effect of SP16 by calculating the AUC for CRP. This is done by measuring CRP at baseline, 72 hours, and 14 days. The AUC will then be compared to historical controls to evaluate whether or not SP16 reduces the AUC for CRP.
Time frame: Baseline, 72 hours, 14 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SP16 | Area Under the Curve (AUC) for C-reactive Protein (CRP) | 133 mg*day/L |
Secondary
Area Under Curve (AUC) for Creatine-Kinase Myocardial Band (CK-MB)
This study will estimate the infarct size based upon area under the curve (AUC) for creatine-kinase myocardial band (CK-MB). The AUC calculation will come from CK-MB levels drawn during usual care. The infarct size will then be compared to historical controls to evaluate whether or not SP16 reduces the infarct size.
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SP16 | Area Under Curve (AUC) for Creatine-Kinase Myocardial Band (CK-MB) | 1432 ng/mL*day |
Secondary
Change in Left Ventricular Ejection Fraction (LVEF) at Baseline and 365 Days
Patients will undergo transthoracic echocardiography at baseline and 365 days to evaluate the change in LVEF.
Time frame: 365 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SP16 | Change in Left Ventricular Ejection Fraction (LVEF) at Baseline and 365 Days | 5 percentage of LVEF |
Secondary
Diagnosis of Heart Failure
Number of participants diagnosed with heart failure at 1 year follow up
Time frame: 365 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SP16 | Diagnosis of Heart Failure | 0 Participants |