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

NCT04463251 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CL04018075
• Study Type: interventional
• Target: 102
• Locations: 2 countries
• Sites: 11

Brief 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)

Conditions

Acute ST Segment Elevation Myocardial Infarction

Keywords

STEMI; Myocardial infarction; Cardiovascular diseases; CVD; Coronary heart disease; CHD

Outcome Measures

Primary Outcomes (4)

• High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure)

  hsCRP area under curve (AUC) from baseline (Day 1) until Day 14

  Day 1 until Day 14

• High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (сomplete Cases)

  hsCRP area under curve (AUC) from baseline (Day 1) until Day 14

  Day 1 until Day 14

• High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Multiple Imputation Procedure)

  hsCRP area under curve (AUC) from baseline (Day 1) until Day 14 (sensitivity analysis)

  Day 1 until Day 14

• High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Complete Cases)

  hsCRP area under curve (AUC) from baseline (Day 1) until Day 14 (sensitivity analysis)

  Day 1 until Day 14

Secondary Outcomes (24)

• hsCRP AUC From Baseline Until Day 28 (Multiple Imputation Procedure)

  up to Day 28

• hsCRP AUC From Baseline Until Day 28 (Complete Cases)

  up to Day 28

• Number of Patients With Fatal Outcomes (Cardiac and Non-cardiac) During 12-month Follow-up Period

  up to Day 365

• Number of Patients With of Hospitalizations Due to Heart Failure (HF) or Other Cardiac Reasons Not Associated With HF, or Due to Non-cardiac Reasons During 12-month Follow-up Period

  up to Day 365

• Number of Patients With New Cases of HF During 12-month Follow-up Period

  up to Day 365

Study Arms (3)

RPH-104 80 mg

EXPERIMENTAL

subjects received subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites

Biological: RPH-104 80 mg; Drug: Placebo

RPH-104 160 mg

EXPERIMENTAL

subjects received subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of (80 mg) of RPH-104 on different administration sites

Biological: RPH-104 80 mg

Placebo

PLACEBO COMPARATOR

subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites

Drug: Placebo

Interventions

RPH-104 80 mg BIOLOGICAL

solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial

Also known as: goflikicept

RPH-104 160 mg; RPH-104 80 mg

Placebo DRUG

Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial

Placebo; RPH-104 80 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• 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;
• intrauterine device or contraceptive system;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• R-Pharm Overseas, Inc.: lead
• Cromos Pharma LLC: collaborator
• Data Management 365: collaborator
• Keystat, LLC: collaborator
• R-Pharm: collaborator
• K-Research, LLC: collaborator

Study Sites (11)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

VCU Health-Virginia Commonwealth University Health

Richmond, Virginia, 23298-5051, United States

Location

State Budgetary Healthcare Institution of Moscow "City Clinical Hospital named after V.V. Vinogradov of Moscow Healthcare Department"

Moscow, 117292, Russia

Location

State Institution of Healthcare in Moscow "City Clinical Hospital № 51 Moscow Health Department"

Moscow, 121309, Russia

Location

Federal State Budgetary Institution "National Medical Research Center for Cardiology" of the Ministry of Healthcare of the Russian Federation

Moscow, 121552, Russia

Location

State Budgetary Healthcare Institution of Moscow "City Clinical Hospital named after V.V. Veresaev of Moscow Healthcare Department"

Moscow, 127644, Russia

Location

State Autonomous Healthcare Institution of the Perm Territory "City Clinical Hospital No. 4"

Perm, 614107, Russia

Location

Ryazan State Medical University n.a. academician I.P. Pavlov on the basis of Regional Clinical cardiology Dispensary

Ryazan, 390026, Russia

Location

St. Petersburg State Budgetary Healthcare Institution "Saint Martyr Elizabeth City Hospital"

Saint Petersburg, 197706, Russia

Location

The State Budgetary Health Care Institution of the Yaroslavl Region "Regional Clinical Hospital"

Yaroslavl, 150062, Russia

Location

Related Publications (2)

• Abbate A, Van Tassell B, Bogin V, Markley R, Pevzner DV, Cremer PC, Meray I, Privalov DV, Taylor A, Grishin SA, Egorova AN, Ponomar EG, Lavrovsky Y, Samsonov MY; RPH-104 STEMI Study Investigators. Results of International, Double-Blind, Randomized, Placebo-Controlled, Phase IIa Study of Interleukin-1 Blockade With RPH-104 (Goflikicept) in Patients With ST-Segment-Elevation Myocardial Infarction (STEMI). Circulation. 2024 Aug 13;150(7):580-582. doi: 10.1161/CIRCULATIONAHA.124.069396. Epub 2024 Aug 12. No abstract available.

  PMID: 39133774 DERIVED

• Samsonov M, Bogin V, Van Tassell BW, Abbate A. Interleukin-1 blockade with RPH-104 in patients with acute ST-elevation myocardial infarction: study design and rationale. J Transl Med. 2021 Apr 26;19(1):169. doi: 10.1186/s12967-021-02828-z.

  PMID: 33902621 DERIVED

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Myocardial Infarction; Cardiovascular Diseases; Coronary Disease

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Results Point of Contact

• Title: Sergey Grishin, Director, Dep. of Clinical Development and Medical Expertise in Autoimmune Diseases
• Organization: R-Pharm

sa.grishin@rpharm.ru

0074959567937

Study Officials

• Yan Lavrovsky

  R-Pharm Overseas, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2020
• First Posted: July 9, 2020
• Study Start: December 7, 2020
• Primary Completion: November 3, 2021
• Study Completion: October 10, 2022
• Last Updated: June 24, 2024
• Results First Posted: January 24, 2024

Record last verified: 2024-05

Locations

US (3); RU (8)