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CompletedNCT04463251Updated Jun 24, 2024Results posted

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 interventional study of RPH-104 80 mg and Placebo in Acute ST Segment Elevation Myocardial Infarction, sponsored by R-Pharm Overseas, Inc.. Completed at 11 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-24.

Sponsored by R-Pharm Overseas, Inc. (part of R-Pharm) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
102
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • Acute ST Segment Elevation Myocardial Infarction

Keywords

  • STEMI
  • Myocardial infarction
  • Cardiovascular diseases
  • CVD
  • Coronary heart disease
  • CHD
03

In context

ST Elevation Myocardial Infarction

688 studies on the registry are indexed under ST Elevation Myocardial Infarction; 184 are open to participants now.

This study's enrollment of 102 is below the median of 194 across 439 interventional studies indexed under ST Elevation Myocardial Infarction.

Browse ST Elevation Myocardial Infarction studies →

Lead sponsor

R-Pharm Overseas, Inc. is the lead sponsor of 3 studies on the registry; none are open to participants now.

Browse R-Pharm Overseas, Inc. studies →All R-Pharm studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
102 participants (actual)

Study arms

  • Experimental
    RPH-104 80 mg

    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

  • Experimental
    RPH-104 160 mg

    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 comparator
    Placebo

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

    Drug: Placebo

Interventions

  • BiologicalRPH-104 80 mg

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

    Also known as: goflikicept

  • DrugPlacebo

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

06

What researchers measure

Primary outcomes

  1. 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

    Time frame: Day 1 until Day 14

  2. 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

    Time frame: Day 1 until Day 14

  3. 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)

    Time frame: Day 1 until Day 14

  4. 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)

    Time frame: Day 1 until Day 14

Secondary outcomes

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

    hsCRP AUC from baseline (Day 1) until Day 28

    Time frame: up to Day 28

  2. hsCRP AUC From Baseline Until Day 28 (Complete Cases)

    hsCRP AUC from baseline (Day 1) until Day 28

    Time frame: up to Day 28

  3. 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.

    Time frame: up to Day 365

  4. 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.

    Time frame: up to Day 365

  5. 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

    Time frame: up to Day 365

  6. 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.

    Time frame: From Day 1 until Day 365

  7. 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.

    Time frame: From Day 1 Until Day 365

  8. BNP AUC From Day 1 (Baseline) Until Day 28

    Time frame: up to Day 28

  9. NT-pro-BNP AUC From Day 1 (Baseline) Until Day 28

    Time frame: up to Day 28

  10. 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

    Time frame: up to Day 365

  11. Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF During 12-month Follow-up Period

    ISOAC assessment

    Time frame: up to Day 365

  12. 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.

    Time frame: From Day 1 until Day 365

  13. 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.

    Time frame: From Day 1 Until Day 365

  14. 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.

    Time frame: From Day 1 Until Day 365

  15. 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.

    Time frame: From Day 1 Until Day 365

  16. 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.

    Time frame: From Day 1 Until Day 365

  17. 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.

    Time frame: From Day 1 Until Day 365

  18. 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.

    Time frame: From Day 1 Until Day 365

  19. 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.

    Time frame: From Day 1 Until Day 365

  20. 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.

    Time frame: From Day 1 Until Day 365

  21. 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.

    Time frame: From Day 1 Until Day 365

  22. 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.

    Time frame: From Day 1 Until Day 365

  23. 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.

    Time frame: From Day 1 Until Day 365

  24. 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.

    Time frame: From Day 1 until Day 28

07

Results

Posted Jan 24, 2024

Participant flow

Patients were enrolled at 11 sites (Russia - 8, USA - 3). A total of 102 patients were randomized. The safety set included all randomized patients.The full analysis set for efficacy analysis (FAS) included 101 patients (who received the study products and underwent at least one hsCRP measurement after administration of the study products. The Per Protocol Set (PPS) included 92 subjects from the FAS without significant protocol deviations affecting assessment of the primary efficacy parameter.

Participant flow — Overall Study
MilestoneRPH-104 80 mgRPH-104 160 mgPlacebo
Started343434
Safety set343434
Full analysis set343433
Per protocol set303131
Completed the study per protocol333031
Completed333031
Not completed143
Withdrew: Death101
Withdrew: Adverse event010
Withdrew: Lost to follow-up010
Withdrew: Withdrawal by subject022

Outcome measures

PrimaryHigh-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

Time frame:
Day 1 until Day 14
Reported as:
Geometric least squares mean · mg*day/L
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure)
mg*day/LRPH-104 80 mgRPH-104 160 mgPlacebo
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure)106.84 (79.72 to 143.19)107.65 (80.10 to 144.68)184.30 (136.06 to 249.65)
Statistical analysis
  • RPH-104 80 mg vs Placebo · Least square means ratio: 0.58 · 95% CI 0.37 to 0.91Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 80 mg / Placebo. Ratio was calculated instead of difference because log data transformation.
  • RPH-104 160 mg vs Placebo · Least square means ratio: 0.58 · 95% CI 0.37 to 0.91Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 160 mg / Placebo. Ratio was calculated instead of difference because log data transformation.
PrimaryHigh-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

Time frame:
Day 1 until Day 14
Reported as:
Geometric least squares mean · mg*day/L
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (сomplete Cases)
mg*day/LRPH-104 80 mgRPH-104 160 mgPlacebo
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (сomplete Cases)96.72 (70.57 to 132.54)106.71 (77.53 to 146.87)178.59 (129.54 to 246.21)
Statistical analysis
  • RPH-104 80 mg vs Placebo · Least square means ratio: 0.54 · 95% CI 0.34 to 0.87Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 80 mg / Placebo. Ratio was calculated instead of difference because log data transformation.
  • RPH-104 160 mg vs Placebo · Least square means ratio: 0.60 · 95% CI 0.37 to 0.95Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 160 mg / Placebo. Ratio was calculated instead of difference because log data transformation.
PrimaryHigh-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)

Time frame:
Day 1 until Day 14
Reported as:
Geometric least squares mean · mg*day/L
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Multiple Imputation Procedure)
mg*day/LRPH-104 80 mgRPH-104 160 mgPlacebo
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Multiple Imputation Procedure)96.57 (69.75 to 133.71)105.30 (76.00 to 145.91)173.48 (124.31 to 242.10)
Statistical analysis
  • RPH-104 80 mg vs Placebo · Least square means ratio: 0.56 · 95% CI 0.34 to 0.91Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 80 mg / Placebo. Ratio was calculated instead of difference because log data transformation
  • RPH-104 160 mg vs Placebo · Least square means ratio: 0.61 · 95% CI 0.38 to 0.98Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 160 mg / Placebo. Ratio was calculated instead of difference because log data transformation.
PrimaryHigh-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)

Time frame:
Day 1 until Day 14
Reported as:
Geometric least squares mean · mg*day/L
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Complete Cases)
mg*day/LRPH-104 80 mgRPH-104 160 mgPlacebo
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Complete Cases)95.35 (68.41 to 132.91)104.26 (75.07 to 144.81)171.69 (122.74 to 240.16)
Statistical analysis
  • RPH-104 80 mg vs Placebo · Least square means ratio: 0.56 · 95% CI 0.34 to 0.91Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 80 mg / Placebo. Ratio was calculated instead of difference because log data transformation
  • RPH-104 160 mg vs Placebo · Least square means ratio: 0.61 · 95% CI 0.38 to 0.98Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 160 mg / Placebo. Ratio was calculated instead of difference because log data transformation.
SecondaryhsCRP AUC From Baseline Until Day 28 (Multiple Imputation Procedure)

hsCRP AUC from baseline (Day 1) until Day 28

Time frame:
up to Day 28
Reported as:
Geometric least squares mean · mg*day/L
hsCRP AUC From Baseline Until Day 28 (Multiple Imputation Procedure)
mg*day/LRPH-104 80 mgRPH-104 160 mgPlacebo
hsCRP AUC From Baseline Until Day 28 (Multiple Imputation Procedure)148.58 (111.62 to 197.79)136.84 (102.44 to 182.78)285.78 (212.21 to 384.86)
Statistical analysis
  • RPH-104 80 mg vs Placebo · Least square means ratio: 0.52 · 95% CI 0.34 to 0.81
  • RPH-104 160 mg vs Placebo · Least square means ratio: 0.48 · 95% CI 0.31 to 0.74Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 160 mg / Placebo. Ratio was calculated instead of difference because log data transformation.
SecondaryhsCRP AUC From Baseline Until Day 28 (Complete Cases)

hsCRP AUC from baseline (Day 1) until Day 28

Time frame:
up to Day 28
Reported as:
Geometric least squares mean · mg*day/L
hsCRP AUC From Baseline Until Day 28 (Complete Cases)
mg*day/LRPH-104 80 mgRPH-104 160 mgPlacebo
hsCRP AUC From Baseline Until Day 28 (Complete Cases)130.07 (95.41 to 177.31)131.27 (95.95 to 179.60)277.13 (202.68 to 378.94)
Statistical analysis
  • RPH-104 80 mg vs Placebo · Least square means ratio: 0.47 · 95% CI 0.29 to 0.75Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 80 mg / Placebo. Ratio was calculated instead of difference because log data transformation.
  • RPH-104 160 mg vs Placebo · Least square means ratio: 0.47 · 95% CI 0.30 to 0.75Least square means ratio with two-sided Dunnett's adjusted 95% CI for RPH-104 160 mg / Placebo. Ratio was calculated instead of difference because log data transformation.
SecondaryNumber 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.

Time frame:
up to Day 365
Reported as:
Count of participants · Participants
Number of Patients With Fatal Outcomes (Cardiac and Non-cardiac) During 12-month Follow-up Period
ParticipantsRPH-104 80 mgRPH-104 160 mgPlacebo
Cardiovascular death101
Non-cardiovascular death000
Patient is alive333130
Unknown032
SecondaryNumber 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.

Time frame:
up to Day 365
Reported as:
Count of participants · Participants
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
ParticipantsRPH-104 80 mgRPH-104 160 mgPlacebo
Hospitalization for cardiovascular reasons (except Heart Failure)203
Hospitalization for new HF onset000
Hospitalization due to non-cardiac reasons211
Unknown (premature discontinuation)032
SecondaryNumber 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

Time frame:
up to Day 365
Reported as:
Count of participants · Participants
Number of Patients With New Cases of HF During 12-month Follow-up Period
ParticipantsRPH-104 80 mgRPH-104 160 mgPlacebo
Number of Patients With New Cases of HF During 12-month Follow-up Period000
SecondaryChanges 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.

Time frame:
From Day 1 until Day 365
Reported as:
Geometric least squares mean · ratio
Changes in Levels of Brain Natriuretic Peptide (BNP) During 12-month Follow-up Period Compared to Baseline
ratioRPH-104 80 mgRPH-104 160 mgPlacebo
Change from baseline (Day 3)1.74 (1.25 to 2.42)1.23 (0.88 to 1.71)1.62 (1.16 to 2.27)
Change from baseline (Day 14)2.04 (1.34 to 3.11)1.27 (0.83 to 1.94)1.52 (1.00 to 2.32)
Change from baseline (Day 28 / Early withdrawal)1.50 (1.50 to 2.37)1.05 (0.67 to 1.66)1.14 (0.72 to 1.81)
Change from baseline (Month 12)0.64 (0.40 to 1.05)0.44 (0.26 to 0.73)0.67 (0.40 to 1.10)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · ml
Changes in End-diastolic (EDV) Volume After 12 Months Compared to Baseline
mlRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)123.92 (115.80 to 132.04)123.10 (114.57 to 131.62)122.64 (114.11 to 131.18)
Day 28 / Early withdrawal123.32 (114.91 to 131.72)126.49 (117.52 to 135.47)132.34 (123.67 to 141.01)
Change from baseline (Day 28 / Early withdrawal)-0.60 (-11.29 to 10.08)3.40 (-7.45 to 14.25)9.70 (-1.33 to 20.72)
Month 12112.80 (104.56 to 121.04)116.88 (107.77 to 125.99)119.98 (111.03 to 128.93)
Change from baseline (Month 12)-11.12 (-22.86 to 0.62)-6.22 (-18.41 to 5.97)-2.66 (-15.20 to 9.88)
SecondaryBNP AUC From Day 1 (Baseline) Until Day 28
Time frame:
up to Day 28
Reported as:
Geometric least squares mean · pmol*day/L
BNP AUC From Day 1 (Baseline) Until Day 28
pmol*day/LRPH-104 80 mgRPH-104 160 mgPlacebo
BNP AUC From Day 1 (Baseline) Until Day 28923.04 (702.30 to 1213.18)833.55 (628.07 to 1106.27)954.22 (725.29 to 1255.42)
SecondaryNT-pro-BNP AUC From Day 1 (Baseline) Until Day 28
Time frame:
up to Day 28
Reported as:
Geometric least squares mean · pmol*day/L
NT-pro-BNP AUC From Day 1 (Baseline) Until Day 28
pmol*day/LRPH-104 80 mgRPH-104 160 mgPlacebo
NT-pro-BNP AUC From Day 1 (Baseline) Until Day 282152.07 (1591.94 to 2909.29)1940.71 (1438.84 to 2617.62)2597.13 (1928.48 to 3497.62)
SecondaryNumber 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

Time frame:
up to Day 365
Reported as:
Count of participants · Participants
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
ParticipantsRPH-104 80 mgRPH-104 160 mgPlacebo
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 Period101
SecondaryNumber of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF During 12-month Follow-up Period

ISOAC assessment

Time frame:
up to Day 365
Reported as:
Count of participants · Participants
Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF During 12-month Follow-up Period
ParticipantsRPH-104 80 mgRPH-104 160 mgPlacebo
Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF During 12-month Follow-up Period101
SecondaryChanges 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.

Time frame:
From Day 1 until Day 365
Reported as:
Geometric least squares mean · ratio
Changes in Levels of Brain Natriuretic Peptide (NT-proBNP) During 12-month Follow-up Period Compared to Baseline
ratioRPH-104 80 mgRPH-104 160 mgPlacebo
Change from baseline (Day 3)2.24 (1.60 to 3.14)1.85 (1.32 to 2.58)2.32 (1.66 to 3.25)
Change from baseline (Day 14)1.70 (1.10 to 2.63)1.28 (0.83 to 1.96)1.59 (1.04 to 2.44)
Change from baseline (Day 28 / Early withdrawal)1.46 (0.90 to 2.37)1.28 (0.80 to 2.06)1.45 (0.90 to 2.34)
Change from baseline (Month 12)0.38 (0.23 to 0.64)0.37 (0.22 to 0.63)0.46 (0.27 to 0.78)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · ml
Changes in End-systolic (ESV) Volume After 12 Months Compared to Baseline
mlRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)54.20 (48.76 to 59.65)54.60 (48.90 to 60.30)54.55 (48.86 to 60.24)
Day 28 / Early withdrawal52.30 (46.67 to 57.93)54.31 (48.32 to 60.30)52.07 (46.29 to 57.85)
Change from baseline (Day 28 / Early withdrawal)-1.90 (-8.90 to 5.09)-0.30 (-7.40 to 6.81)-2.47 (-9.69 to 4.74)
Month 1245.88 (40.35 to 51.40)48.67 (42.58 to 54.75)48.67 (42.71 to 54.63)
Change from baseline (Month 12)-8.33 (-16.06 to -0.59)-5.94 (-13.97 to 2.10)-5.88 (-14.15 to 2.39)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · percentage of blood
Changes in Ejection Fraction (EF) After 12 Months Compared to Baseline
percentage of bloodRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)56.93 (54.61 to 59.25)56.51 (54.12 to 58.89)56.62 (54.19 to 59.05)
Day 28 / Early withdrawal58.98 (56.57 to 61.39)58.35 (55.82 to 60.88)61.26 (58.79 to 63.73)
Change from baseline (Day 28 / Early withdrawal)2.05 (-2.02 to 6.13)1.84 (-2.27 to 5.96)4.64 (0.41 to 8.87)
Month 1260.87 (58.52 to 63.22)60.31 (57.74 to 62.88)61.17 (58.61 to 63.72)
Change from baseline (Month 12)3.94 (0.16 to 7.72)3.80 (-0.10 to 7.70)4.55 (0.52 to 8.58)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · index units
Changes in Regional LV Function After 12 Months Compared to Baseline
index unitsRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)1.40 (1.32 to 1.48)1.39 (1.31 to 1.47)1.40 (1.32 to 1.49)
Day 28 / Early withdrawal1.23 (1.14 to 1.31)1.29 (1.20 to 1.37)1.21 (1.12 to 1.30)
Change from baseline (Day 28 / Early withdrawal)-0.17 (-0.29 to -0.06)-0.10 (-0.21 to 0.01)-0.19 (-0.31 to -0.07)
Month 121.19 (1.09 to 1.28)1.26 (1.15 to 1.37)1.17 (1.06 to 1.29)
Change from baseline (Month 12)-0.21 (-0.34 to -0.08)-0.13 (-0.27 to 0.01)-0.23 (-0.38 to -0.08)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · ml
Changes in Stroke Volume (SV) Compared to Baseline
mlRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)70.09 (65.34 to 74.83)68.15 (63.22 to 73.07)67.61 (62.64 to 72.59)
Day 28 / Early withdrawal71.05 (66.11 to 75.99)71.62 (66.39 to 76.86)79.79 (74.72 to 84.86)
Change from baseline (Day 28 / Early withdrawal)0.96 (-6.18 to 8.10)3.48 (-3.75 to 10.71)12.17 (4.81 to 19.54)
Month 1266.09 (61.28 to 70.90)67.61 (62.31 to 72.91)70.63 (65.37 to 75.89)
Change from baseline (Month 12)-4.00 (-11.38 to 3.38)-0.54 (-8.19 to 7.11)3.02 (-4.88 to 10.91)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · percentage of myocardial shortening
Changes in Global Longitudinal Strain (GLS) Compared to Baseline
percentage of myocardial shorteningRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)-15.39 (-16.50 to -14.28)-15.24 (-16.42 to -14.07)-14.60 (-15.80 to -13.40)
Day 28 / Early withdrawal-16.69 (-17.88 to -15.50)-16.20 (-17.46 to -14.94)-18.22 (-19.47 to -16.96)
Change from baseline (Day 28 / Early withdrawal)-1.30 (-3.03 to 0.43)-0.96 (-2.72 to 0.81)-3.62 (-5.48 to -1.76)
Month 12-17.80 (-18.99 to -16.62)-18.16 (-19.54 to -16.78)-19.47 (-20.81 to -18.13)
Change from baseline (Month 12)-2.41 (-4.20 to -0.63)-2.91 (-4.85 to -0.98)-4.87 (-6.86 to -2.87)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · percentage of area
Changes of Fractional Area Change (FAC) Compared to Baseline
percentage of areaRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)48.65 (45.11 to 52.19)48.45 (45.25 to 51.65)48.93 (45.30 to 52.56)
Day 28 / Early withdrawal51.73 (47.73 to 55.74)50.78 (47.03 to 54.53)50.27 (46.34 to 54.19)
Change from baseline (Day 28 / Early withdrawal)3.09 (-2.78 to 8.95)2.33 (-2.90 to 7.56)1.34 (-4.59 to 7.26)
Month 1249.22 (44.45 to 53.98)51.32 (46.97 to 55.66)48.15 (43.13 to 53.16)
Change from baseline (Month 12)0.57 (-6.07 to 7.21)2.87 (-2.98 to 8.72)-0.78 (-7.75 to 6.18)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · mm
Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) Parameter Compared to Baseline
mmRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)21.87 (20.46 to 23.29)21.76 (20.43 to 23.08)21.19 (19.87 to 22.51)
Day 28 / Early withdrawal22.09 (20.61 to 23.56)22.71 (21.22 to 24.21)22.79 (21.37 to 24.21)
Change from baseline (Day 28 / Early withdrawal)0.21 (-2.08 to 2.50)0.96 (-1.22 to 3.13)1.60 (-0.57 to 3.76)
Month 1221.88 (20.40 to 23.36)21.05 (19.42 to 22.69)22.71 (21.26 to 24.16)
Change from baseline (Month 12)0.00 (-2.29 to 2.30)-0.70 (-3.01 to 1.60)1.52 (-0.68 to 3.72)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · m/s
Changes in Early Diastolic Transmitral Flow Velocity (E Velocity) Compared to Baseline
m/sRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)0.72 (0.67 to 0.77)0.70 (0.65 to 0.75)0.70 (0.65 to 0.75)
Day 28 / Early withdrawal0.72 (0.67 to 0.77)0.69 (0.63 to 0.74)0.79 (0.74 to 0.84)
Change from baseline (Day 28 / Early withdrawal)-0.00 (-0.09 to 0.08)-0.01 (-0.10 to 0.08)0.09 (-0.00 to 0.18)
Month 120.67 (0.62 to 0.72)0.70 (0.64 to 0.75)0.76 (0.71 to 0.82)
Change from baseline (Month 12)-0.05 (-0.13 to 0.03)-0.00 (-0.09 to 0.08)0.06 (-0.02 to 0.14)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · cm/s
Changes in Mitral Valve (MV) e'Sept Compared to Baseline
cm/sRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)7.17 (6.68 to 7.67)7.14 (6.62 to 7.65)6.69 (6.17 to 7.21)
Day 28 / Early withdrawal6.47 (5.96 to 6.99)7.03 (6.49 to 7.57)7.09 (6.55 to 7.63)
Change from baseline (Day 28 / Early withdrawal)-0.70 (-1.46 to 0.06)-0.11 (-0.87 to 0.65)0.40 (-0.39 to 1.18)
Month 126.51 (5.98 to 7.04)7.11 (6.55 to 7.68)7.11 (6.55 to 7.67)
Change from baseline (Month 12)-0.66 (-1.45 to 0.13)-0.02 (-0.83 to 0.79)0.42 (-0.42 to 1.26)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · cm/s
Changes in Mitral Valve e'Lat Compared to Baseline
cm/sRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)9.04 (8.32 to 9.76)9.04 (8.28 to 9.81)8.76 (8.01 to 9.51)
Day 28 / Early withdrawal9.55 (8.79 to 10.31)8.86 (8.06 to 9.67)9.61 (8.81 to 10.40)
Change from baseline (Day 28 / Early withdrawal)0.51 (-0.61 to 1.64)-0.18 (-1.33 to 0.97)0.85 (-0.32 to 2.02)
Month 129.24 (8.49 to 9.99)9.83 (9.00 to 10.66)9.63 (8.82 to 10.44)
Change from baseline (Month 12)0.20 (-0.94 to 1.35)0.79 (-0.42 to 2.00)0.87 (-0.35 to 2.09)
SecondaryChanges 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.

Time frame:
From Day 1 Until Day 365
Reported as:
Least squares mean · ml
Changes in Left Ventricular Stroke Volume (LV SV) Compared to Baseline
mlRPH-104 80 mgRPH-104 160 mgPlacebo
Day 1 (Baseline)66.18 (61.40 to 70.96)67.25 (62.49 to 72.02)65.09 (59.74 to 70.45)
Day 28 / Early withdrawal67.97 (63.04 to 72.91)71.33 (66.16 to 76.50)76.55 (70.52 to 82.57)
Change from baseline (Day 28 / Early withdrawal)1.79 (-5.60 to 9.18)4.08 (-3.16 to 11.32)11.45 (2.73 to 20.18)
Month 1274.14 (68.94 to 79.33)71.11 (65.62 to 76.60)73.12 (67.31 to 78.92)
Change from baseline (Month 12)7.95 (0.11 to 15.80)3.86 (-3.92 to 11.63)8.02 (-0.68 to 16.73)
SecondaryChanges 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.

Time frame:
From Day 1 until Day 28
Reported as:
Geometric least squares mean · ratio
Changes in hsCRP Levels During the Study Compared to Baseline
ratioRPH-104 80 mgRPH-104 160 mgPlacebo
Change from baseline (Day 3)2.54 (1.64 to 3.94)2.81 (1.81 to 4.35)3.75 (2.40 to 5.85)
Change from baseline (Day 14)0.31 (0.18 to 0.51)0.22 (0.13 to 0.37)1.54 (0.92 to 2.59)
Change from baseline (Day 28 / Early withdrawal)0.34 (0.20 to 0.58)0.23 (0.13 to 0.39)0.56 (0.33 to 0.97)

Adverse events

Collected over 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".). Non-serious events are listed at a 4% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
RPH-104 80 mg1/34 (2.9%)7/34 (20.6%)21/34 (61.8%)
RPH-104 160 mg0/34 (0%)1/34 (2.9%)20/34 (58.8%)
Placebo1/34 (2.9%)4/34 (11.8%)14/34 (41.2%)
Pre-treatment Monitoring of "RPH-104 80 mg" Group0/34 (0%)0/34 (0%)3/34 (8.8%)
Pre-treatment Monitoring of "RPH-104 160 mg" Group0/34 (0%)0/34 (0%)3/34 (8.8%)
Pre-treatment Monitoring of Placebo Group0/34 (0%)0/34 (0%)2/34 (5.9%)
Most frequent serious events
Showing 10 of 12
Most frequent serious events
EventRPH-104 80 mgRPH-104 160 mgPlaceboPre-treatment Monitoring of "RPH-104 80 mg" GroupPre-treatment Monitoring of "RPH-104 160 mg" GroupPre-treatment Monitoring of Placebo Group
Angina unstableCardiac disorders0/340/342/340/340/340/34
Atrial fibrillationCardiac disorders1/340/340/340/340/340/34
Atrioventricular block completeCardiac disorders1/340/340/340/340/340/34
Gastric disorderGastrointestinal disorders0/340/341/340/340/340/34
Gastric haemorrhageGastrointestinal disorders1/340/340/340/340/340/34
Cardiac deathGeneral disorders1/340/340/340/340/340/34
Non-cardiac chest painGeneral disorders1/340/340/340/340/340/34
Sudden cardiac deathGeneral disorders0/340/341/340/340/340/34
Cholecystitis acuteHepatobiliary disorders0/341/340/340/340/340/34
COVID-19 pneumoniaInfections and infestations1/340/340/340/340/340/34
Most frequent other events
Showing 10 of 24
Most frequent other events
EventRPH-104 80 mgRPH-104 160 mgPlaceboPre-treatment Monitoring of "RPH-104 80 mg" GroupPre-treatment Monitoring of "RPH-104 160 mg" GroupPre-treatment Monitoring of Placebo Group
Brachiocephalic arteriosclerosisVascular disorders6/346/348/340/340/340/34
AstheniaGeneral disorders1/344/345/340/340/340/34
COVID-19Infections and infestations4/341/341/340/340/340/34
N-terminal prohormone brain natriuretic peptide increasedInvestigations4/342/340/343/343/342/34
FatigueGeneral disorders3/342/341/340/340/340/34
Non-cardiac chest painGeneral disorders3/340/340/340/340/340/34
LymphopeniaBlood and lymphatic system disorders2/342/340/340/340/340/34
Atrial fibrillationCardiac disorders0/342/341/340/340/340/34
Cardiac failure acuteCardiac disorders2/341/340/340/340/340/34
Cardiac failure chronicCardiac disorders1/340/342/340/340/340/34

Baseline characteristics

Age, Continuous
Age, Continuous(years)RPH-104 80 mgRPH-104 160 mgPlaceboTotal
Mean58.9 (33 to 79)58.7 (38 to 86)59.3 (23 to 88)59 (23 to 88)
Sex: Female, Male
Sex: Female, Male(Participants)RPH-104 80 mgRPH-104 160 mgPlaceboTotal
Female1151228
Male23292173
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)RPH-104 80 mgRPH-104 160 mgPlaceboTotal
Race — Asian1001
Race — Black or African American3003
Race — White29343396
Race — Hispanic1001
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)RPH-104 80 mgRPH-104 160 mgPlaceboTotal
Mean28.7 (20.7 to 39.2)29.4 (20.3 to 49.1)30.3 (22.3 to 42.0)29.5 (20.3 to 49.1)
08

Study locations

11 sites
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • University of Virginia Health System
    Charlottesville, Virginia 22908, United States
  • VCU Health-Virginia Commonwealth University Health
    Richmond, Virginia 23298-5051, United States
  • State Budgetary Healthcare Institution of Moscow "City Clinical Hospital named after V.V. Vinogradov of Moscow Healthcare Department"
    Moscow, 117292, Russia
  • State Institution of Healthcare in Moscow "City Clinical Hospital № 51 Moscow Health Department"
    Moscow, 121309, Russia
  • Federal State Budgetary Institution "National Medical Research Center for Cardiology" of the Ministry of Healthcare of the Russian Federation
    Moscow, 121552, Russia
  • State Budgetary Healthcare Institution of Moscow "City Clinical Hospital named after V.V. Veresaev of Moscow Healthcare Department"
    Moscow, 127644, Russia
  • State Autonomous Healthcare Institution of the Perm Territory "City Clinical Hospital No. 4"
    Perm, 614107, Russia
  • Ryazan State Medical University n.a. academician I.P. Pavlov on the basis of Regional Clinical cardiology Dispensary
    Ryazan, 390026, Russia
  • St. Petersburg State Budgetary Healthcare Institution "Saint Martyr Elizabeth City Hospital"
    Saint Petersburg, 197706, Russia
  • The State Budgetary Health Care Institution of the Yaroslavl Region "Regional Clinical Hospital"
    Yaroslavl, 150062, Russia
09

References and documents

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 ↗

Study documents

  • Protocol and statistical analysis plan · Oct 27, 2021

Documents are hosted by the registry — open the source record to download them.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 24, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT04463251
Lead sponsor
R-Pharm Overseas, Inc.
Collaborators
Cromos Pharma LLC, Data Management 365, Keystat, LLC, R-Pharm, K-Research, LLC
Responsible party
Sponsor
First posted
Jul 9, 2020
Start date
Dec 7, 2020
Primary completion
Nov 3, 2021
Completion
Oct 10, 2022
Results posted
Jan 24, 2024
Last update
Jun 24, 2024

Study contacts

Yan Lavrovsky
study director · R-Pharm Overseas, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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