Study to Evaluate the Effect on Parameters of Systemic Inflammation and Disease Outcomes and Safety of RPH-104 in Subjects With Acute ST-elevation Myocardial Infarction
Condition: Acute ST Segment Elevation Myocardial Infarction
MeSH terms: Myocardial Infarction; ST Elevation Myocardial Infarction; Inflammation; Infarction
Intervention: RPH-104 80 mg; Placebo
Intervention description: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial; Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: STEMI; Myocardial infarction; Cardiovascular diseases; CVD; Coronary heart disease; CHD

Summary:

      The goal of the study was to evaluate the effect of single administration of RPH-104 at 80 mg
      and 160 mg on parameters of systemic inflammation and outcomes of the disease in subjects
      with ST-segment elevation myocardial infarction (STEMI)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who gave voluntary written Informed consent to participate in the study and
             to follow all Protocol procedures.

          -  STEMI diagnosis defined as chest pain or its equivalent with ECG findings evidencing
             ST elevation (>1 mm) in two or more consecutive leads or acute left bunch branch block
             according the investigator's judgement.

          -  Percutaneous coronary intervention (PCI) with stenting was performed within no more
             than 12 hours after onset of chest pain or its equivalent and randomization was
             performed in no more than 12 hours after PCI (overall within 24 hours of onset of
             chest pain or equivalent).

          -  Consent of female subjects with childbearing potential defined as all female subjects
             with physiological potential to conceive, to use highly effective contraceptive
             methods throughout the study starting from screening (signing Informed Consent Form)
             and negative pregnancy test.

        Highly effective contraceptive methods include combination of two of the following methods
        (a+b or a+c or b+c):

          1. oral, injection or implanted hormonal contraceptives; in case of oral contraceptives,
             the female subjects should administer the same product for at least 3 months prior to
             the study therapy;

          2. intrauterine device or contraceptive system;

          3. barrier methods: condom or occlusive cap (diaphragm or cervical cap / vaginal fornix
             cap) with spermicidal foam/gel/film/cream/vaginal suppository

               -  Ability and willingness of the subject, according to the reasonable
                  investigator's judgment, to attend the study site at all scheduled visits,
                  undergo the study procedures and follow the Protocol requirements including
                  subcutaneous injections by qualified site personnel.

        Exclusion Criteria:

          -  Hypersensitivity to test product (RPH-104) and/or its ingredients/excipients.

          -  Pregnancy and breastfeeding.

          -  Verified chronic heart failure (The American Heart Association / The American College
             of Cardiology (AHA/ACC) C-D class, New York Heart Association (NYHA) Functional class
             (FC) III-IV)

          -  Pre-existing severe valvular heart disease according to the investigator's assessment.

          -  Pre-existing left ventricular (LV) dysfunction (ejection fraction (EF)<40%)

          -  History of STEMI

          -  Complications of acute myocardial infarction (MI) in the form of acute left
             ventricular failure and cardiogenic shock defined as stable blood pressure decrease
             (SBP<90 mm Hg) associated with signs of hypoperfusion as well as cases when inotropic
             and/or mechanical support is required to maintain SBP; and / or unstable hemodynamics.

          -  Active infections (acute or chronic); active tuberculosis.

          -  Recent (less than 5 half-life periods) or current administration of colchicine, as
             well as agents with an immunosuppressant mechanism of action, including, but not
             limited to:

        glucocorticoids at doses of > 1 mg/kg of methylprednisolone equivalent, tumor necrosis
        factor-alfa (TNFα) blockers, Interleukin-1 (IL-1) and other biological drugs, cyclosporine
        and other immunosuppressants. Non-steroidal anti-inflammatory drugs (NSAIDs) are allowed.

          -  Immunization with live vaccines within 90 days prior to the study product
             administration.

          -  Chronic systemic autoimmune or autoinflammatory diseases

          -  Suspected necessity in cardiosurgery.

          -  Oncology (or diagnosis of oncology within the last 5 years).

          -  History of organ transplantation or necessity in transplantation at the screening
             initiation or scheduled transplantation during the study.

          -  Neutropenia (absolute neutrophil count <1800/mm^3).

          -  Participation in another clinical study within the previous 3 months prior to
             Screening visit.

          -  Other medical (including mental) conditions or abnormal laboratory findings which may
             increase the risk for the subject associated with the study participation or
             administration of the study products or which may affect interpretation of the study
             results and, according to the investigator, render the subject ineligible for the
             study.*

             *If, in the Investigator's opinion, administration of a non-live COVID-19 (SARS-CoV-2)
             vaccine increases the risk for the patient related to his/her participation in the
             study, the Investigator can make a decision not to include this patient into the
             study.

          -  The subjects working at the study site or subjects working for Sponsor directly
             involved in this clinical study.