SP16 Inflammatory Response Inhibition Trial (SPIRIT)

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Inflammation
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SP16; Patients will receive a single dose of SP16 0.2 mg/kg by subcutaneous injection	Drug: SP16; All patients will receive a single dose of SP16

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 72 hours, 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	72 hours
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.	365 days
Diagnosis of Heart Failure	Number of participants diagnosed with heart failure at 1 year follow up	365 days

Collaborators and Investigators

• Sponsor: Serpin Pharma, LLC
• Collaborators: Virginia Commonwealth University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Actual): January 4, 2021
• Study Completion (Actual): December 21, 2021

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 4, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Inflammation
• Other Study ID Numbers: HM20018201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No