Clinical trial NCT04225533: SP16 Inflammatory Response Inhibition Trial
Official title: SP16 Inflammatory Response Inhibition Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Myocardial Infarction
Inflammation
Lead sponsor: Serpin Pharma, LLC
Sponsor class: OTHER
Collaborators: name: Virginia Commonwealth University
First posted: 2020-01-13
Enrollment: 10
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Area Under the Curve (AUC) for C-reactive Protein (CRP)
timeFrame: Baseline, 72 hours, 14 days
Secondary outcomes:
measure: Area Under Curve (AUC) for Creatine-Kinase Myocardial Band (CK-MB)
timeFrame: 72 hours
measure: Change in Left Ventricular Ejection Fraction (LVEF) at Baseline and 365 Days
timeFrame: 365 days
measure: Diagnosis of Heart Failure
timeFrame: 365 days
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Antonio Abbate, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Van Tassell BW, Wohlford GF, Del Buono MG, Damonte JI, Markley R, Turlington J, Kadariya D, Talasaz A, Ho J, Marawan A, Thomas GK, Austin D, Gineste C, Gelber C, Abbate A. Safety, Tolerability, and Effects of a Single Subcutaneous Administration of SP16 - a SERPIN-like, Small Peptide Agonist of the Low-Density Lipoprotein-like Receptor 1- on the Acute Inflammatory Response in Patients With ST-Segment Elevation Myocardial Infarction. J Cardiovasc Pharmacol. 2022 Nov 1;80(5):672-678. doi: 10.1097/FJC.0000000000001331.