Acute ST Segment Elevation Myocardial InfarctionPhase 2NCT04463251

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

A Phase 2 study testing RPH-104 80 mg in people with Acute ST Segment Elevation Myocardial Infarction, run by R-Pharm Overseas, Inc. at 11 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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) Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute ST Segment Elevation Myocardial Infarction
What is being tested?: RPH-104 80 mg
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 102 participants
Where: 11 sitesin 2 countries
Study dates: 7 Dec 2020to 10 Oct 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

Show all 9Show fewer

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.

Who cannot join

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

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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.

Trial locations and contacts

11 sites in 2 countries.

Country

City, postcode or hospital

11 sites in 2 countries

Russia8 sites

State Budgetary Healthcare Institution of Moscow "City Clinical Hospital named after V.V. Vinogradov of Moscow Healthcare Department"
Moscow, 117292
State Institution of Healthcare in Moscow "City Clinical Hospital № 51 Moscow Health Department"
Moscow, 121309
Federal State Budgetary Institution "National Medical Research Center for Cardiology" of the Ministry of Healthcare of the Russian Federation
Moscow, 121552
State Budgetary Healthcare Institution of Moscow "City Clinical Hospital named after V.V. Veresaev of Moscow Healthcare Department"
Moscow, 127644
State Autonomous Healthcare Institution of the Perm Territory "City Clinical Hospital No. 4"
Perm, 614107
Ryazan State Medical University n.a. academician I.P. Pavlov on the basis of Regional Clinical cardiology Dispensary
Ryazan, 390026
St. Petersburg State Budgetary Healthcare Institution "Saint Martyr Elizabeth City Hospital"
Saint Petersburg, 197706
The State Budgetary Health Care Institution of the Yaroslavl Region "Regional Clinical Hospital"
Yaroslavl, 150062

Other trials in Russia

United States3 sites

University of Virginia Health System
Charlottesville, Virginia, 22908
Cleveland Clinic
Cleveland, Ohio, 44195
VCU Health-Virginia Commonwealth University Health
Richmond, Virginia, 23298-5051

Other trials in United States

About this study

Official title: International, Double Blind, Randomized, Placebo-controlled 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

Read the detailed description

After signing the informed consent form, the investigator assessed the subject's eligibility for the study. The following procedures were performed during the screening: collection of medical history, recording previous and concomitant therapy, demographic data, recording 12-lead ECG findings on which STEMI diagnosis was based, recording date and time of STEMI symptom development, recording date, time and results of coronary angiography (CAG) at admission to the study site, measurement of blood neutrophil count, vital signs, physical examination including measurement of body weight (if hospital bed is available), blood sampling for hematology, biochemistry, determination of concentration of hsCRP and brain natriuretic peptide (BNP; N-terminal (NT)-pro hormone brain natriuretic peptide (NT-pro-BNP)), for females with retained reproductive potential - pregnancy test (test strips).

The subjects meeting selection criteria were randomized to one of the three groups (in 1:1:1 ratio) for single subcutaneous administration of RPH-104 80 mg, RPH-104 160 mg or placebo.

Screening, randomization and administration of the study products were made on the same (first) study day.

Further 4-week (28-day) clinical follow-up and additional 6- and 12-month clinical follow-up period were performed.

The end of clinical part of the study was the date of the last visit of the last subject within additional 12-month clinical follow-up.

The maximum number of screened patients was planned to be 146 subjects, 102 subjects were randomized, 34 subjects per group.

Conditions: Acute ST Segment Elevation Myocardial Infarction
Being tested: RPH-104 80 mg, Placebo
Keywords: STEMI, Myocardial infarction, Cardiovascular diseases, CVD, Coronary heart disease, CHD
Medical subject headings: ST Elevation Myocardial Infarction, Myocardial Infarction, Cardiovascular Diseases, Coronary Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RPH-104 80 mgBiological
Also called goflikicept
solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial
PlaceboDrug
Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial

Study groups in NCT04463251
Study group	Role	What they receive
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 Receives: 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 Receives: 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 Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 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)
Measured: 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)
Measured: Day 1 until Day 14

Secondary outcomes (24)

hsCRP AUC From Baseline Until Day 28 (Multiple Imputation Procedure)
hsCRP AUC from baseline (Day 1) until Day 28
Measured: up to Day 28
hsCRP AUC From Baseline Until Day 28 (Complete Cases)
hsCRP AUC from baseline (Day 1) until Day 28
Measured: up to Day 28
Number of Patients With Fatal Outcomes (Cardiac and Non-cardiac) During 12-month Follow-up Period
Any fatal outcomes were evaluated by the investigators and Independent study outcome assessment committee (ISOAC). ISOAC assessments were considered as the main data for conclusions, the investigator's assessments were presented for informational purposes only.
Measured: 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
Number of patients with hospitalizations for any reason during 12-month follow-up period, assessed by ISOAC.
Measured: up to Day 365
Number of Patients With New Cases of HF During 12-month Follow-up Period
New cases of HF are defined as hospitalization due to HF or an emergency outpatient visit due to heart failure.
ISOAC assessment
Measured: up to Day 365
Changes in Levels of Brain Natriuretic Peptide (BNP) During 12-month Follow-up Period Compared to Baseline
Change in levels of BNP during 12-month follow-up period compared to baseline. (Brain Natriuretic Peptide (BNP) was measured in pmol/L.) Increased levels of BNP can be considered as marker of hemodynamic stress and surrogate marker of Heart Failure.
The reported Least square means and confidence interval were from a repeated measures model on log transformed BNP data containing treatment, visit as factors, log baseline BNP as a continuous covariate and treatment by visit as interaction terms. Due to log-transformed data, change from baseline was defined as division value at corresponding time point and baseline value, thus the smallest value of the change from baseline indicates a better outcome or improvement.
Measured: From Day 1 until Day 365
Changes in End-diastolic (EDV) Volume After 12 Months Compared to Baseline
Apical 4-, 2-, and 3-chamber view in B-mode: End-diastolic (EDV) volumes. Measured by echocardiography (Echo-CG) (in mL). The reported Least square means and confidence interval were from a repeated measures model on EDV data containing treatment, visit as factors, baseline EDV as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
BNP AUC From Day 1 (Baseline) Until Day 28
Measured: up to Day 28
NT-pro-BNP AUC From Day 1 (Baseline) Until Day 28
Measured: up to Day 28
Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF or Emergency Outpatient Visits Due to HF During 12-month Follow-up Period
ISOAC assessment
Measured: up to Day 365
Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF During 12-month Follow-up Period
ISOAC assessment
Measured: up to Day 365
Changes in Levels of Brain Natriuretic Peptide (NT-proBNP) During 12-month Follow-up Period Compared to Baseline
Change in levels of NT-proBNP during 12-month follow-up period compared to baseline.
The reported Least square means and confidence interval were from a repeated measures model on log transformed NT-proBNP data containing treatment, visit as factors, log transformed baseline NT-proBNP as a continuous covariate and treatment by visit as interaction terms.
For log-transformed data change was defined as division value at corresponding time point and baseline value.
Measured: From Day 1 until Day 365
Changes in End-systolic (ESV) Volume After 12 Months Compared to Baseline
Apical 4-, 2-, and 3-chamber view in B-mode: End-systolic (ESV) volumes. Measured by echocardiography (Echo-CG) (in mL). The reported Least square means and confidence interval were from a repeated measures model on ESV data containing treatment, visit as factors, baseline ESV as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in Ejection Fraction (EF) After 12 Months Compared to Baseline
Apical 4-, 2-, and 3-chamber view in B-mode: Ejection fraction (EF) (Simpson method).
Measured by echocardiography (Echo-CG) (in percentage). The reported Least square means and confidence interval were from a repeated measures model on EF data containing treatment, visit as factors, baseline EF as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in Regional LV Function After 12 Months Compared to Baseline
Apical 4-, 2-, and 3-chamber view in B-mode: assessment of regional LV function using the wall motion score index (WMSI), measured by Echo-CG.
The wall motion score index was calculated by assigning each segment a score based on its systolic function (normal = 1 (the best), hypokinesis = 2, akinesis = 3, dyskinesis = 4 (the worst)). The WMSI is the sum of all segmental scores divided by the number of segments analyzed (scale 1 - 4). A wall motion score index of 1 is normal (the best outcome). The higher the wall motion score index the worse is the outcome.
The reported Least square means and confidence interval were from a repeated measures model on Regional LV Function data containing treatment, visit as factors, baseline Regional LV Function data as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in Stroke Volume (SV) Compared to Baseline
Apical 4-, 2-, and 3-chamber view in B-mode: assessment of Stroke Volume (SV), measured by Echo-CG.
The reported Least square means and confidence interval were from a repeated measures model on SV data containing treatment, visit as factors, baseline SV data as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in Global Longitudinal Strain (GLS) Compared to Baseline
Apical 4-, 2-, and 3-chamber view in B-mode: assessment of Global Longitudinal Strain (GLS), measured by Echo-CG.
GLS is a measure of longitudinal shortening of the myocardium as a percentage (change in length as a proportion to baseline length), thus explaining the negative values.
The reported Least square means and confidence interval were from a repeated measures model on GLS data containing treatment, visit as factors, baseline GLS data as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes of Fractional Area Change (FAC) Compared to Baseline
Right atrium and ventricle assessment from the apical 4-chamber right ventricular-focused view (with maximal right ventricular basal dimension) in B-mode and M-mode: Fractional Area Change (FAC).
The reported Least square means and confidence interval were from a repeated measures model on FAC data containing treatment, visit as factors, baseline FAC data as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) Parameter Compared to Baseline
Right atrium and ventricle assessment from the apical 4-chamber right ventricular-focused view (with maximal right ventricular basal dimension) in B-mode and M-mode: tricuspid annular plane systolic excursion (TAPSE).
The reported Least square means and confidence interval were from a repeated measures model on TAPSE data containing treatment, visit as factors, baseline TAPSE data as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in Early Diastolic Transmitral Flow Velocity (E Velocity) Compared to Baseline
Assessment of diastolic and systolic function, apical 4-chamber view in pulse-wave Doppler mode, tissue Doppler mode: Transmitral flow, pulsed wave (PW) Doppler, E.
The reported Least square means and confidence interval were from a repeated measures model on E velocity data containing treatment, visit as factors, baseline E velocity data as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in Mitral Valve (MV) e'Sept Compared to Baseline
Assessment of diastolic and systolic function, apical 4-chamber view in pulse-wave Doppler mode, tissue Doppler mode: Tissue Doppler Imaging, MV e'sept. Unit of measure is centimeter/second (cm/s). This is one of the diastolic function parameters (septal velocity fibrous ring of the mitral valve (MV)).
The reported Least square means and confidence interval were from a repeated measures model on MV e'Sept data containing treatment, visit as factors, baseline MV e'Sept data as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in Mitral Valve e'Lat Compared to Baseline
Assessment of diastolic and systolic function, apical 4-chamber view in pulse-wave Doppler mode, tissue Doppler mode: Tissue Doppler Imaging, MV e'lat. Unit of measure is centimeter/second (cm/s). This is one of the diastolic function parameters (lateral velocity of fibrous ring of the mitral valve (MV)).
The reported Least square means and confidence interval were from a repeated measures model on MV e'Lat data containing treatment, visit as factors, baseline MV e'Lat data as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in Left Ventricular Stroke Volume (LV SV) Compared to Baseline
Assessment of diastolic and systolic function, apical 4-chamber view in pulse-wave Doppler mode, tissue Doppler mode: LV outflow tract velocity-time integral (VTI) + Diameter. Tissue Doppler Imaging, LV Stroke Volume (pulse-wave Doppler mode).
The reported Least square means and confidence interval were from a repeated measures model on LV SV data containing treatment, visit as factors, baseline LV SV data as a continuous covariate and treatment by visit as interaction terms.
Measured: From Day 1 Until Day 365
Changes in hsCRP Levels During the Study Compared to Baseline
Change in levels of hsCRP during the study compared to baseline. The reported Least square means and confidence interval were from a repeated measures model on log transformed hsCRP data containing treatment, visit as factors, log transformed baseline hsCRP data as a continuous covariate and treatment by visit as interaction terms.
For log-transformed data change was defined as division value at corresponding time point and baseline value.
Measured: From Day 1 until Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Dec 202010 Oct 2022

First posted9 Jul 2020
Study start7 Dec 2020
Primary completion3 Nov 2021
Study completion10 Oct 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Acute ST Segment Elevation Myocardial InfarctionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 102 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04463251
Sponsor's protocol ID: CL04018075
Status last verified: May 2024
First submitted: 3 Jul 2020
Last updated: 24 Jun 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 39133774
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.
PubMed 33902621

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Acute ST Segment Elevation Myocardial Infarction trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: International, Double Blind, Randomized, Placebo-controlled 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
ClinicalTrials.gov ID: NCT04463251
Acronym / sponsor ID: CL04018075
Conditions: Acute ST Segment Elevation Myocardial Infarction
Keywords: STEMI, Myocardial infarction, Cardiovascular diseases, CVD, Coronary heart disease, CHD
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 102 participants (actual)
Lead sponsor: R-Pharm Overseas, Inc.Industry (pharma, biotech, devices)
Collaborators: Cromos Pharma LLC, Data Management 365, Keystat, LLC, R-Pharm, K-Research, LLC
Study start: 7 Dec 2020 (actual)
Primary completion: 3 Nov 2021 (actual)
Study completion: 10 Oct 2022 (actual)
First posted: 9 Jul 2020 (actual)
Results: Posted 24 Jan 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The subjects meeting selection criteria were randomized to one of the three groups (in 1:1:1 ratio) for single subcutaneous administration of RPH-104 80 mg, RPH-104 160 mg or placebo.

Screening, randomization and administration of the study products were made on the same (first) study day.

Further 4-week (28-day) clinical follow-up and additional 6- and 12-month clinical follow-up period were performed.

The end of clinical part of the study was the date of the last visit of the last subject within additional 12-month clinical follow-up.

The maximum number of screened patients was planned to be 146 subjects, 102 subjects were randomized, 34 subjects per group.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
RPH-104 80 mg	Experimental	Biological: RPH-104 80 mg, Drug: Placebosubjects received subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites
RPH-104 160 mg	Experimental	Biological: RPH-104 80 mgsubjects 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
Placebo	Placebo comparator	Drug: Placebosubjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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):

Key exclusion criteria (20 listed)

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%)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RPH-104 80 mgAlso: goflikiceptsolution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Biological	RPH-104 160 mg, RPH-104 80 mg
PlaceboNormal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	Drug	Placebo, RPH-104 80 mg

Primary outcome

High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure)
Time frame: Day 1 until Day 14
hsCRP area under curve (AUC) from baseline (Day 1) until Day 14
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (сomplete Cases)
Time frame: Day 1 until Day 14
hsCRP area under curve (AUC) from baseline (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)
Time frame: Day 1 until Day 14
hsCRP area under curve (AUC) from baseline (Day 1) until Day 14 (sensitivity analysis)
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Complete Cases)
Time frame: Day 1 until Day 14
hsCRP area under curve (AUC) from baseline (Day 1) until Day 14 (sensitivity analysis)

24 secondary outcomes

hsCRP AUC From Baseline Until Day 28 (Multiple Imputation Procedure)
Time frame: up to Day 28
hsCRP AUC From Baseline Until Day 28 (Complete Cases)
Time frame: up to Day 28
Number of Patients With Fatal Outcomes (Cardiac and Non-cardiac) During 12-month Follow-up Period
Time frame: 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
Time frame: up to Day 365
Number of Patients With New Cases of HF During 12-month Follow-up Period
Time frame: up to Day 365
Changes in Levels of Brain Natriuretic Peptide (BNP) During 12-month Follow-up Period Compared to Baseline
Time frame: From Day 1 until Day 365
Changes in End-diastolic (EDV) Volume After 12 Months Compared to Baseline
Time frame: From Day 1 Until Day 365
BNP AUC From Day 1 (Baseline) Until Day 28
Time frame: up to Day 28
NT-pro-BNP AUC From Day 1 (Baseline) Until Day 28
Time frame: up to Day 28
Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF or Emergency Outpatient Visits Due to HF During 12-month Follow-up Period
Time frame: up to Day 365
Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF During 12-month Follow-up Period
Time frame: up to Day 365
Changes in Levels of Brain Natriuretic Peptide (NT-proBNP) During 12-month Follow-up Period Compared to Baseline
Time frame: From Day 1 until Day 365
Changes in End-systolic (ESV) Volume After 12 Months Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in Ejection Fraction (EF) After 12 Months Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in Regional LV Function After 12 Months Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in Stroke Volume (SV) Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in Global Longitudinal Strain (GLS) Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes of Fractional Area Change (FAC) Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) Parameter Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in Early Diastolic Transmitral Flow Velocity (E Velocity) Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in Mitral Valve (MV) e'Sept Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in Mitral Valve e'Lat Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in Left Ventricular Stroke Volume (LV SV) Compared to Baseline
Time frame: From Day 1 Until Day 365
Changes in hsCRP Levels During the Study Compared to Baseline
Time frame: From Day 1 until Day 28

Results and safety

Results posted to the registry on 24 Jan 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
RPH-104 80 mg	34	33
RPH-104 160 mg	34	30
Placebo	34	31

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

Time frame: Day 1 until Day 14. Geometric least squares mean (95% Confidence Interval). Unit: mg*day/L

Measure	RPH-104 80 mg n = 34	RPH-104 160 mg n = 34	Placebo n = 33
Value	106.84 (79.72 to 143.19)	107.65 (80.10 to 144.68)	184.30 (136.06 to 249.65)

RPH-104 80 mg vs Placebo: Least square means ratio: 0.58 (95% CI 0.37 to 0.91)
RPH-104 160 mg vs Placebo: Least square means ratio: 0.58 (95% CI 0.37 to 0.91)

Population analysed: Full analysis set for efficacy analysis included all randomized subjects who received the study products (RPH-104 or placebo), and underwent at least one hsCRP measurement after administration of the study products. The FAS was the main population for efficacy assessment. Multiple imputation procedure was performed for hsCRP values which were missed on Day 14.

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

Time frame: Day 1 until Day 14. Geometric least squares mean (95% Confidence Interval). Unit: mg*day/L

Measure	RPH-104 80 mg n = 34	RPH-104 160 mg n = 34	Placebo n = 33
Value	96.72 (70.57 to 132.54)	106.71 (77.53 to 146.87)	178.59 (129.54 to 246.21)

RPH-104 80 mg vs Placebo: Least square means ratio: 0.54 (95% CI 0.34 to 0.87)
RPH-104 160 mg vs Placebo: Least square means ratio: 0.60 (95% CI 0.37 to 0.95)

Population analysed: Full analysis set for efficacy analysis included all randomized subjects who received the study products (RPH-104 or placebo), and underwent at least one hsCRP measurement after administration of the study products. The FAS was the main population for efficacy assessment. The model included patients with complete data (complete cases) in the FAS population. No data imputations were performed.

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

Time frame: Day 1 until Day 14. Geometric least squares mean (95% Confidence Interval). Unit: mg*day/L

Measure	RPH-104 80 mg n = 30	RPH-104 160 mg n = 31	Placebo n = 31
Value	96.57 (69.75 to 133.71)	105.30 (76.00 to 145.91)	173.48 (124.31 to 242.10)

RPH-104 80 mg vs Placebo: Least square means ratio: 0.56 (95% CI 0.34 to 0.91)
RPH-104 160 mg vs Placebo: Least square means ratio: 0.61 (95% CI 0.38 to 0.98)

Population analysed: At the stage of final analysis, sensitivity analysis was performed for the per protocol population (PPS). Multiple imputation procedure was performed for hsCRP values which were missed on Day 14.

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

Time frame: Day 1 until Day 14. Geometric least squares mean (95% Confidence Interval). Unit: mg*day/L

Measure	RPH-104 80 mg n = 30	RPH-104 160 mg n = 31	Placebo n = 31
Value	95.35 (68.41 to 132.91)	104.26 (75.07 to 144.81)	171.69 (122.74 to 240.16)

RPH-104 80 mg vs Placebo: Least square means ratio: 0.56 (95% CI 0.34 to 0.91)
RPH-104 160 mg vs Placebo: Least square means ratio: 0.61 (95% CI 0.38 to 0.98)

Population analysed: At the stage of final analysis, sensitivity analysis was performed for the per protocol population (PPS). The model included patients with complete data (complete cases) in the PPS population. No data imputations were performed.

24 secondary outcomes are reported in the full results.

Adverse events

Time frame: Information on all Adverse Events (AEs) was collected since signing informed consent form (ICF) and until the study completion by the subject (up to day 365). SAEs for every participant were recorded since his/her signing ICF and for up to 30 days after the study product treatment discontinuation or until the last visit of the participant whichever is the latter, assessed up to 365 days. (AEs recorded prior to the study product administration were added to eCRF section "Medical history".). Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
RPH-104 80 mg	7 of 34 (20.6%)	21 of 34 (61.8%)	1 of 34
RPH-104 160 mg	1 of 34 (2.9%)	20 of 34 (58.8%)	0 of 34
Placebo	4 of 34 (11.8%)	14 of 34 (41.2%)	1 of 34
Pre-treatment Monitoring of "RPH-104 80 mg" Group	0 of 34 (0%)	3 of 34 (8.8%)	0 of 34
Pre-treatment Monitoring of "RPH-104 160 mg" Group	0 of 34 (0%)	3 of 34 (8.8%)	0 of 34
Pre-treatment Monitoring of Placebo Group	0 of 34 (0%)	2 of 34 (5.9%)	0 of 34

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39133774Abbate 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.
Derived from this study: PubMed 33902621Samsonov 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Yan Lavrovsky study director

R-Pharm Overseas, Inc.

11 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RPH-104 80 mg in people with Acute ST Segment Elevation Myocardial Infarction, run by R-Pharm Overseas, Inc. at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Russia, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure) (time frame: Day 1 until Day 14). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04463251, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2024.