Trial Outcomes & Findings for 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 (NCT NCT04463251)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

102 participants

Primary outcome timeframe

Day 1 until Day 14

Results posted on

2024-06-24

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 milestones

Participant milestones
Measure	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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Overall Study STARTED	34	34	34
Overall Study Safety Set	34	34	34
Overall Study Full Analysis Set	34	34	33
Overall Study Per Protocol Set	30	31	31
Overall Study Completed the Study Per Protocol	33	30	31
Overall Study COMPLETED	33	30	31
Overall Study NOT COMPLETED	1	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Overall Study Death	1	0	1
Overall Study Adverse Event	0	1	0
Overall Study Lost to Follow-up	0	1	0
Overall Study Withdrawal by Subject	0	2	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RPH-104 80 mg n=34 Participants subjects received subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	Total n=101 Participants Total of all reporting groups
Age, Continuous	58.9 years n=5 Participants	58.7 years n=7 Participants	59.3 years n=5 Participants	59 years n=4 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants	28 Participants n=4 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	29 Participants n=7 Participants	21 Participants n=5 Participants	73 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	3 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	29 Participants n=5 Participants	34 Participants n=7 Participants	33 Participants n=5 Participants	96 Participants n=4 Participants
Race/Ethnicity, Customized Race · Hispanic	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Body Mass Index (BMI)	28.7 kg/m^2 n=5 Participants	29.4 kg/m^2 n=7 Participants	30.3 kg/m^2 n=5 Participants	29.5 kg/m^2 n=4 Participants

PRIMARY outcome

Timeframe: Day 1 until Day 14

Population: 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.

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

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Multiple Imputation Procedure)	106.84 mg*day/L Interval 79.72 to 143.19	107.65 mg*day/L Interval 80.1 to 144.68	184.30 mg*day/L Interval 136.06 to 249.65

PRIMARY outcome

Timeframe: Day 1 until Day 14

Population: 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.

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

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (сomplete Cases)	96.72 mg*day/L Interval 70.57 to 132.54	106.71 mg*day/L Interval 77.53 to 146.87	178.59 mg*day/L Interval 129.54 to 246.21

PRIMARY outcome

Timeframe: Day 1 until Day 14

Population: 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.

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

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=30 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=31 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=31 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Multiple Imputation Procedure)	96.57 mg*day/L Interval 69.75 to 133.71	105.30 mg*day/L Interval 76.0 to 145.91	173.48 mg*day/L Interval 124.31 to 242.1

PRIMARY outcome

Timeframe: Day 1 until Day 14

Population: 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.

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

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=30 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=31 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=31 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
High-sensitive С-reactive Protein (hsCRP) Area Under Curve (AUC) From Baseline Until Day 14 (Sensitivity Analysis, Complete Cases)	95.35 mg*day/L Interval 68.41 to 132.91	104.26 mg*day/L Interval 75.07 to 144.81	171.69 mg*day/L Interval 122.74 to 240.16

SECONDARY outcome

Timeframe: up to Day 28

Population: 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 28.

hsCRP AUC from baseline (Day 1) until Day 28

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
hsCRP AUC From Baseline Until Day 28 (Multiple Imputation Procedure)	148.58 mg*day/L Interval 111.62 to 197.79	136.84 mg*day/L Interval 102.44 to 182.78	285.78 mg*day/L Interval 212.21 to 384.86

SECONDARY outcome

Timeframe: up to Day 28

Population: 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.

hsCRP AUC from baseline (Day 1) until Day 28

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
hsCRP AUC From Baseline Until Day 28 (Complete Cases)	130.07 mg*day/L Interval 95.41 to 177.31	131.27 mg*day/L Interval 95.95 to 179.6	277.13 mg*day/L Interval 202.68 to 378.94

SECONDARY outcome

Timeframe: up to Day 365

Population: Analysis was performed at the stage of final analysis for the FAS population. Data for fatal cases (deaths) were derived from CRF records. The CRF provided "Yes", "No" and "Unknown" for patient's alive status. Unknown was naturally missing data.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Number of Patients With Fatal Outcomes (Cardiac and Non-cardiac) During 12-month Follow-up Period Cardiovascular death	1 Participants	0 Participants	1 Participants
Number of Patients With Fatal Outcomes (Cardiac and Non-cardiac) During 12-month Follow-up Period Non-cardiovascular death	0 Participants	0 Participants	0 Participants
Number of Patients With Fatal Outcomes (Cardiac and Non-cardiac) During 12-month Follow-up Period Patient is alive	33 Participants	31 Participants	30 Participants
Number of Patients With Fatal Outcomes (Cardiac and Non-cardiac) During 12-month Follow-up Period Unknown	0 Participants	3 Participants	2 Participants

SECONDARY outcome

Timeframe: up to Day 365

Population: Analysis was performed at the stage of final analysis for the FAS population.

Number of patients with hospitalizations for any reason during 12-month follow-up period, assessed by ISOAC.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
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 Hospitalization for cardiovascular reasons (except Heart Failure)	2 Participants	0 Participants	3 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 Hospitalization for new HF onset	0 Participants	0 Participants	0 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 Hospitalization due to non-cardiac reasons	2 Participants	1 Participants	1 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 Unknown (premature discontinuation)	0 Participants	3 Participants	2 Participants

SECONDARY outcome

Timeframe: up to Day 365

Population: FAS population

New cases of HF are defined as hospitalization due to HF or an emergency outpatient visit due to heart failure. ISOAC assessment

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Number of Patients With New Cases of HF During 12-month Follow-up Period	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 1 until Day 365

Population: Analysis was performed at the stage of final analysis for the FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Levels of Brain Natriuretic Peptide (BNP) During 12-month Follow-up Period Compared to Baseline Change from baseline (Day 3)	1.74 ratio Interval 1.25 to 2.42	1.23 ratio Interval 0.88 to 1.71	1.62 ratio Interval 1.16 to 2.27
Changes in Levels of Brain Natriuretic Peptide (BNP) During 12-month Follow-up Period Compared to Baseline Change from baseline (Day 14)	2.04 ratio Interval 1.34 to 3.11	1.27 ratio Interval 0.83 to 1.94	1.52 ratio Interval 1.0 to 2.32
Changes in Levels of Brain Natriuretic Peptide (BNP) During 12-month Follow-up Period Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	1.50 ratio Interval 1.5 to 2.37	1.05 ratio Interval 0.67 to 1.66	1.14 ratio Interval 0.72 to 1.81
Changes in Levels of Brain Natriuretic Peptide (BNP) During 12-month Follow-up Period Compared to Baseline Change from baseline (Month 12)	0.64 ratio Interval 0.4 to 1.05	0.44 ratio Interval 0.26 to 0.73	0.67 ratio Interval 0.4 to 1.1

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in End-diastolic (EDV) Volume After 12 Months Compared to Baseline Day 1 (Baseline)	123.92 ml Interval 115.8 to 132.04	123.10 ml Interval 114.57 to 131.62	122.64 ml Interval 114.11 to 131.18
Changes in End-diastolic (EDV) Volume After 12 Months Compared to Baseline Day 28 / Early withdrawal	123.32 ml Interval 114.91 to 131.72	126.49 ml Interval 117.52 to 135.47	132.34 ml Interval 123.67 to 141.01
Changes in End-diastolic (EDV) Volume After 12 Months Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	-0.60 ml Interval -11.29 to 10.08	3.40 ml Interval -7.45 to 14.25	9.70 ml Interval -1.33 to 20.72
Changes in End-diastolic (EDV) Volume After 12 Months Compared to Baseline Month 12	112.80 ml Interval 104.56 to 121.04	116.88 ml Interval 107.77 to 125.99	119.98 ml Interval 111.03 to 128.93
Changes in End-diastolic (EDV) Volume After 12 Months Compared to Baseline Change from baseline (Month 12)	-11.12 ml Interval -22.86 to 0.62	-6.22 ml Interval -18.41 to 5.97	-2.66 ml Interval -15.2 to 9.88

SECONDARY outcome

Timeframe: up to Day 28

Population: 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).

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
BNP AUC From Day 1 (Baseline) Until Day 28	923.04 pmol*day/L Interval 702.3 to 1213.18	833.55 pmol*day/L Interval 628.07 to 1106.27	954.22 pmol*day/L Interval 725.29 to 1255.42

SECONDARY outcome

Timeframe: up to Day 28

Population: 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).

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
NT-pro-BNP AUC From Day 1 (Baseline) Until Day 28	2152.07 pmol*day/L Interval 1591.94 to 2909.29	1940.71 pmol*day/L Interval 1438.84 to 2617.62	2597.13 pmol*day/L Interval 1928.48 to 3497.62

SECONDARY outcome

Timeframe: up to Day 365

Population: FAS population

ISOAC assessment

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
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	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: up to Day 365

Population: FAS population

ISOAC assessment

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Number of Patients With Fatal Outcomes (Due to Any Reason) or Hospitalizations Due to HF During 12-month Follow-up Period	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From Day 1 until Day 365

Population: Analysis was performed at the stage of final analysis for the FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Levels of Brain Natriuretic Peptide (NT-proBNP) During 12-month Follow-up Period Compared to Baseline Change from baseline (Day 3)	2.24 ratio Interval 1.6 to 3.14	1.85 ratio Interval 1.32 to 2.58	2.32 ratio Interval 1.66 to 3.25
Changes in Levels of Brain Natriuretic Peptide (NT-proBNP) During 12-month Follow-up Period Compared to Baseline Change from baseline (Day 14)	1.70 ratio Interval 1.1 to 2.63	1.28 ratio Interval 0.83 to 1.96	1.59 ratio Interval 1.04 to 2.44
Changes in Levels of Brain Natriuretic Peptide (NT-proBNP) During 12-month Follow-up Period Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	1.46 ratio Interval 0.9 to 2.37	1.28 ratio Interval 0.8 to 2.06	1.45 ratio Interval 0.9 to 2.34
Changes in Levels of Brain Natriuretic Peptide (NT-proBNP) During 12-month Follow-up Period Compared to Baseline Change from baseline (Month 12)	0.38 ratio Interval 0.23 to 0.64	0.37 ratio Interval 0.22 to 0.63	0.46 ratio Interval 0.27 to 0.78

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in End-systolic (ESV) Volume After 12 Months Compared to Baseline Day 1 (Baseline)	54.20 ml Interval 48.76 to 59.65	54.60 ml Interval 48.9 to 60.3	54.55 ml Interval 48.86 to 60.24
Changes in End-systolic (ESV) Volume After 12 Months Compared to Baseline Day 28 / Early withdrawal	52.30 ml Interval 46.67 to 57.93	54.31 ml Interval 48.32 to 60.3	52.07 ml Interval 46.29 to 57.85
Changes in End-systolic (ESV) Volume After 12 Months Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	-1.90 ml Interval -8.9 to 5.09	-0.30 ml Interval -7.4 to 6.81	-2.47 ml Interval -9.69 to 4.74
Changes in End-systolic (ESV) Volume After 12 Months Compared to Baseline Month 12	45.88 ml Interval 40.35 to 51.4	48.67 ml Interval 42.58 to 54.75	48.67 ml Interval 42.71 to 54.63
Changes in End-systolic (ESV) Volume After 12 Months Compared to Baseline Change from baseline (Month 12)	-8.33 ml Interval -16.06 to -0.59	-5.94 ml Interval -13.97 to 2.1	-5.88 ml Interval -14.15 to 2.39

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Ejection Fraction (EF) After 12 Months Compared to Baseline Day 28 / Early withdrawal	58.98 percentage of blood Interval 56.57 to 61.39	58.35 percentage of blood Interval 55.82 to 60.88	61.26 percentage of blood Interval 58.79 to 63.73
Changes in Ejection Fraction (EF) After 12 Months Compared to Baseline Day 1 (Baseline)	56.93 percentage of blood Interval 54.61 to 59.25	56.51 percentage of blood Interval 54.12 to 58.89	56.62 percentage of blood Interval 54.19 to 59.05
Changes in Ejection Fraction (EF) After 12 Months Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	2.05 percentage of blood Interval -2.02 to 6.13	1.84 percentage of blood Interval -2.27 to 5.96	4.64 percentage of blood Interval 0.41 to 8.87
Changes in Ejection Fraction (EF) After 12 Months Compared to Baseline Month 12	60.87 percentage of blood Interval 58.52 to 63.22	60.31 percentage of blood Interval 57.74 to 62.88	61.17 percentage of blood Interval 58.61 to 63.72
Changes in Ejection Fraction (EF) After 12 Months Compared to Baseline Change from baseline (Month 12)	3.94 percentage of blood Interval 0.16 to 7.72	3.80 percentage of blood Interval -0.1 to 7.7	4.55 percentage of blood Interval 0.52 to 8.58

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Regional LV Function After 12 Months Compared to Baseline Day 1 (Baseline)	1.40 index units Interval 1.32 to 1.48	1.39 index units Interval 1.31 to 1.47	1.40 index units Interval 1.32 to 1.49
Changes in Regional LV Function After 12 Months Compared to Baseline Day 28 / Early withdrawal	1.23 index units Interval 1.14 to 1.31	1.29 index units Interval 1.2 to 1.37	1.21 index units Interval 1.12 to 1.3
Changes in Regional LV Function After 12 Months Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	-0.17 index units Interval -0.29 to -0.06	-0.10 index units Interval -0.21 to 0.01	-0.19 index units Interval -0.31 to -0.07
Changes in Regional LV Function After 12 Months Compared to Baseline Month 12	1.19 index units Interval 1.09 to 1.28	1.26 index units Interval 1.15 to 1.37	1.17 index units Interval 1.06 to 1.29
Changes in Regional LV Function After 12 Months Compared to Baseline Change from baseline (Month 12)	-0.21 index units Interval -0.34 to -0.08	-0.13 index units Interval -0.27 to 0.01	-0.23 index units Interval -0.38 to -0.08

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Stroke Volume (SV) Compared to Baseline Day 1 (Baseline)	70.09 ml Interval 65.34 to 74.83	68.15 ml Interval 63.22 to 73.07	67.61 ml Interval 62.64 to 72.59
Changes in Stroke Volume (SV) Compared to Baseline Day 28 / Early withdrawal	71.05 ml Interval 66.11 to 75.99	71.62 ml Interval 66.39 to 76.86	79.79 ml Interval 74.72 to 84.86
Changes in Stroke Volume (SV) Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	0.96 ml Interval -6.18 to 8.1	3.48 ml Interval -3.75 to 10.71	12.17 ml Interval 4.81 to 19.54
Changes in Stroke Volume (SV) Compared to Baseline Month 12	66.09 ml Interval 61.28 to 70.9	67.61 ml Interval 62.31 to 72.91	70.63 ml Interval 65.37 to 75.89
Changes in Stroke Volume (SV) Compared to Baseline Change from baseline (Month 12)	-4.00 ml Interval -11.38 to 3.38	-0.54 ml Interval -8.19 to 7.11	3.02 ml Interval -4.88 to 10.91

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Global Longitudinal Strain (GLS) Compared to Baseline Day 1 (Baseline)	-15.39 percentage of myocardial shortening Interval -16.5 to -14.28	-15.24 percentage of myocardial shortening Interval -16.42 to -14.07	-14.60 percentage of myocardial shortening Interval -15.8 to -13.4
Changes in Global Longitudinal Strain (GLS) Compared to Baseline Day 28 / Early withdrawal	-16.69 percentage of myocardial shortening Interval -17.88 to -15.5	-16.20 percentage of myocardial shortening Interval -17.46 to -14.94	-18.22 percentage of myocardial shortening Interval -19.47 to -16.96
Changes in Global Longitudinal Strain (GLS) Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	-1.30 percentage of myocardial shortening Interval -3.03 to 0.43	-0.96 percentage of myocardial shortening Interval -2.72 to 0.81	-3.62 percentage of myocardial shortening Interval -5.48 to -1.76
Changes in Global Longitudinal Strain (GLS) Compared to Baseline Month 12	-17.80 percentage of myocardial shortening Interval -18.99 to -16.62	-18.16 percentage of myocardial shortening Interval -19.54 to -16.78	-19.47 percentage of myocardial shortening Interval -20.81 to -18.13
Changes in Global Longitudinal Strain (GLS) Compared to Baseline Change from baseline (Month 12)	-2.41 percentage of myocardial shortening Interval -4.2 to -0.63	-2.91 percentage of myocardial shortening Interval -4.85 to -0.98	-4.87 percentage of myocardial shortening Interval -6.86 to -2.87

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes of Fractional Area Change (FAC) Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	3.09 percentage of area Interval -2.78 to 8.95	2.33 percentage of area Interval -2.9 to 7.56	1.34 percentage of area Interval -4.59 to 7.26
Changes of Fractional Area Change (FAC) Compared to Baseline Month 12	49.22 percentage of area Interval 44.45 to 53.98	51.32 percentage of area Interval 46.97 to 55.66	48.15 percentage of area Interval 43.13 to 53.16
Changes of Fractional Area Change (FAC) Compared to Baseline Change from baseline (Month 12)	0.57 percentage of area Interval -6.07 to 7.21	2.87 percentage of area Interval -2.98 to 8.72	-0.78 percentage of area Interval -7.75 to 6.18
Changes of Fractional Area Change (FAC) Compared to Baseline Day 1 (Baseline)	48.65 percentage of area Interval 45.11 to 52.19	48.45 percentage of area Interval 45.25 to 51.65	48.93 percentage of area Interval 45.3 to 52.56
Changes of Fractional Area Change (FAC) Compared to Baseline Day 28 / Early withdrawal	51.73 percentage of area Interval 47.73 to 55.74	50.78 percentage of area Interval 47.03 to 54.53	50.27 percentage of area Interval 46.34 to 54.19

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) Parameter Compared to Baseline Day 1 (Baseline)	21.87 mm Interval 20.46 to 23.29	21.76 mm Interval 20.43 to 23.08	21.19 mm Interval 19.87 to 22.51
Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) Parameter Compared to Baseline Day 28 / Early withdrawal	22.09 mm Interval 20.61 to 23.56	22.71 mm Interval 21.22 to 24.21	22.79 mm Interval 21.37 to 24.21
Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) Parameter Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	0.21 mm Interval -2.08 to 2.5	0.96 mm Interval -1.22 to 3.13	1.60 mm Interval -0.57 to 3.76
Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) Parameter Compared to Baseline Month 12	21.88 mm Interval 20.4 to 23.36	21.05 mm Interval 19.42 to 22.69	22.71 mm Interval 21.26 to 24.16
Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) Parameter Compared to Baseline Change from baseline (Month 12)	0.00 mm Interval -2.29 to 2.3	-0.70 mm Interval -3.01 to 1.6	1.52 mm Interval -0.68 to 3.72

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Early Diastolic Transmitral Flow Velocity (E Velocity) Compared to Baseline Day 1 (Baseline)	0.72 m/s Interval 0.67 to 0.77	0.70 m/s Interval 0.65 to 0.75	0.70 m/s Interval 0.65 to 0.75
Changes in Early Diastolic Transmitral Flow Velocity (E Velocity) Compared to Baseline Day 28 / Early withdrawal	0.72 m/s Interval 0.67 to 0.77	0.69 m/s Interval 0.63 to 0.74	0.79 m/s Interval 0.74 to 0.84
Changes in Early Diastolic Transmitral Flow Velocity (E Velocity) Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	-0.00 m/s Interval -0.09 to 0.08	-0.01 m/s Interval -0.1 to 0.08	0.09 m/s Interval 0.0 to 0.18
Changes in Early Diastolic Transmitral Flow Velocity (E Velocity) Compared to Baseline Month 12	0.67 m/s Interval 0.62 to 0.72	0.70 m/s Interval 0.64 to 0.75	0.76 m/s Interval 0.71 to 0.82
Changes in Early Diastolic Transmitral Flow Velocity (E Velocity) Compared to Baseline Change from baseline (Month 12)	-0.05 m/s Interval -0.13 to 0.03	-0.00 m/s Interval -0.09 to 0.08	0.06 m/s Interval -0.02 to 0.14

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Mitral Valve (MV) e'Sept Compared to Baseline Day 1 (Baseline)	7.17 cm/s Interval 6.68 to 7.67	7.14 cm/s Interval 6.62 to 7.65	6.69 cm/s Interval 6.17 to 7.21
Changes in Mitral Valve (MV) e'Sept Compared to Baseline Day 28 / Early withdrawal	6.47 cm/s Interval 5.96 to 6.99	7.03 cm/s Interval 6.49 to 7.57	7.09 cm/s Interval 6.55 to 7.63
Changes in Mitral Valve (MV) e'Sept Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	-0.70 cm/s Interval -1.46 to 0.06	-0.11 cm/s Interval -0.87 to 0.65	0.40 cm/s Interval -0.39 to 1.18
Changes in Mitral Valve (MV) e'Sept Compared to Baseline Month 12	6.51 cm/s Interval 5.98 to 7.04	7.11 cm/s Interval 6.55 to 7.68	7.11 cm/s Interval 6.55 to 7.67
Changes in Mitral Valve (MV) e'Sept Compared to Baseline Change from baseline (Month 12)	-0.66 cm/s Interval -1.45 to 0.13	-0.02 cm/s Interval -0.83 to 0.79	0.42 cm/s Interval -0.42 to 1.26

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Mitral Valve e'Lat Compared to Baseline Day 1 (Baseline)	9.04 cm/s Interval 8.32 to 9.76	9.04 cm/s Interval 8.28 to 9.81	8.76 cm/s Interval 8.01 to 9.51
Changes in Mitral Valve e'Lat Compared to Baseline Day 28 / Early withdrawal	9.55 cm/s Interval 8.79 to 10.31	8.86 cm/s Interval 8.06 to 9.67	9.61 cm/s Interval 8.81 to 10.4
Changes in Mitral Valve e'Lat Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	0.51 cm/s Interval -0.61 to 1.64	-0.18 cm/s Interval -1.33 to 0.97	0.85 cm/s Interval -0.32 to 2.02
Changes in Mitral Valve e'Lat Compared to Baseline Month 12	9.24 cm/s Interval 8.49 to 9.99	9.83 cm/s Interval 9.0 to 10.66	9.63 cm/s Interval 8.82 to 10.44
Changes in Mitral Valve e'Lat Compared to Baseline Change from baseline (Month 12)	0.20 cm/s Interval -0.94 to 1.35	0.79 cm/s Interval -0.42 to 2.0	0.87 cm/s Interval -0.35 to 2.09

SECONDARY outcome

Timeframe: From Day 1 Until Day 365

Population: FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in Left Ventricular Stroke Volume (LV SV) Compared to Baseline Day 1 (Baseline)	66.18 ml Interval 61.4 to 70.96	67.25 ml Interval 62.49 to 72.02	65.09 ml Interval 59.74 to 70.45
Changes in Left Ventricular Stroke Volume (LV SV) Compared to Baseline Day 28 / Early withdrawal	67.97 ml Interval 63.04 to 72.91	71.33 ml Interval 66.16 to 76.5	76.55 ml Interval 70.52 to 82.57
Changes in Left Ventricular Stroke Volume (LV SV) Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	1.79 ml Interval -5.6 to 9.18	4.08 ml Interval -3.16 to 11.32	11.45 ml Interval 2.73 to 20.18
Changes in Left Ventricular Stroke Volume (LV SV) Compared to Baseline Month 12	74.14 ml Interval 68.94 to 79.33	71.11 ml Interval 65.62 to 76.6	73.12 ml Interval 67.31 to 78.92
Changes in Left Ventricular Stroke Volume (LV SV) Compared to Baseline Change from baseline (Month 12)	7.95 ml Interval 0.11 to 15.8	3.86 ml Interval -3.92 to 11.63	8.02 ml Interval -0.68 to 16.73

SECONDARY outcome

Timeframe: From Day 1 until Day 28

Population: Analysis was performed at the stage of final analysis for the FAS population. No data imputations were performed. Here, "Number Analyzed" indicates patients with assessable date each corresponding time point. Change from baseline was calculated for patients who had data at baseline and corresponding time point.

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.

Outcome measures

Outcome measures
Measure	RPH-104 80 mg n=34 Participants subjects receive subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 Participants 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=33 Participants subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial
Changes in hsCRP Levels During the Study Compared to Baseline Change from baseline (Day 3)	2.54 ratio Interval 1.64 to 3.94	2.81 ratio Interval 1.81 to 4.35	3.75 ratio Interval 2.4 to 5.85
Changes in hsCRP Levels During the Study Compared to Baseline Change from baseline (Day 14)	0.31 ratio Interval 0.18 to 0.51	0.22 ratio Interval 0.13 to 0.37	1.54 ratio Interval 0.92 to 2.59
Changes in hsCRP Levels During the Study Compared to Baseline Change from baseline (Day 28 / Early withdrawal)	0.34 ratio Interval 0.2 to 0.58	0.23 ratio Interval 0.13 to 0.39	0.56 ratio Interval 0.33 to 0.97

Adverse Events

RPH-104 80 mg

Serious events: 7 serious events

Other events: 21 other events

Deaths: 1 deaths

RPH-104 160 mg

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 14 other events

Deaths: 1 deaths

Pre-treatment Monitoring of "RPH-104 80 mg" Group

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Pre-treatment Monitoring of "RPH-104 160 mg" Group

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Pre-treatment Monitoring of Placebo Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RPH-104 80 mg n=34 participants at risk subjects received subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 participants at risk 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=34 participants at risk subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	Pre-treatment Monitoring of "RPH-104 80 mg" Group n=34 participants at risk subjects randomized to group "RPH-104 80 mg" assessed between the date of the patient being enrolled in the study (by signing the ICF) and the time of application of randomized treatment (before receiving the target treatment)	Pre-treatment Monitoring of "RPH-104 160 mg" Group n=34 participants at risk subjects randomized to group "RPH-104 160 mg" assessed between the date of the patient being enrolled in the study (by signing the ICF) and the time of application of randomized treatment (before receiving the target treatment)	Pre-treatment Monitoring of Placebo Group n=34 participants at risk subjects randomized to placebo group assessed between the date of the patient being enrolled in the study (by signing the ICF) and the time of application of randomized treatment (before receiving the target treatment)
Cardiac disorders Angina unstable	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Cardiac disorders Atrial fibrillation	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Cardiac disorders Atrioventricular block complete	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Gastrointestinal disorders Gastric disorder	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Gastrointestinal disorders Gastric haemorrhage	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
General disorders Cardiac death	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
General disorders Non-cardiac chest pain	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
General disorders Sudden cardiac death	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Hepatobiliary disorders Cholecystitis acute	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Infections and infestations COVID-19 pneumonia	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Nervous system disorders Syncope	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Nervous system disorders Vascular encephalopathy	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).

Other adverse events

Other adverse events
Measure	RPH-104 80 mg n=34 participants at risk subjects received subcutaneous single injection of 2 mL (80 mg) of RPH-104 and 2 mL of placebo on different administration sites RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	RPH-104 160 mg n=34 participants at risk 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 RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL transparent glass vial	Placebo n=34 participants at risk subjects received subcutaneous single injection of 2 mL of placebo and 2 mL of placebo on different administration sites Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), 2 mL in the 4-mL transparent glass vial	Pre-treatment Monitoring of "RPH-104 80 mg" Group n=34 participants at risk subjects randomized to group "RPH-104 80 mg" assessed between the date of the patient being enrolled in the study (by signing the ICF) and the time of application of randomized treatment (before receiving the target treatment)	Pre-treatment Monitoring of "RPH-104 160 mg" Group n=34 participants at risk subjects randomized to group "RPH-104 160 mg" assessed between the date of the patient being enrolled in the study (by signing the ICF) and the time of application of randomized treatment (before receiving the target treatment)	Pre-treatment Monitoring of Placebo Group n=34 participants at risk subjects randomized to placebo group assessed between the date of the patient being enrolled in the study (by signing the ICF) and the time of application of randomized treatment (before receiving the target treatment)
Blood and lymphatic system disorders Lymphopenia	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 3 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Cardiac disorders Atrial fibrillation	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 3 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Cardiac disorders Cardiac failure acute	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Cardiac disorders Cardiac failure chronic	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Cardiac disorders Cardiac ventricular thrombosis	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
General disorders Asthenia	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	11.8% 4/34 • Number of events 4 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	14.7% 5/34 • Number of events 5 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
General disorders Fatigue	8.8% 3/34 • Number of events 7 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 3 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
General disorders Non-cardiac chest pain	8.8% 3/34 • Number of events 3 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Infections and infestations COVID-19	11.8% 4/34 • Number of events 4 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Infections and infestations Respiratory tract infection	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Infections and infestations Respiratory tract infection viral	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Investigations Alanine aminotransferase increased	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Investigations Aspartate aminotransferase increased	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Investigations Brain natriuretic peptide increased	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Investigations Gamma-glutamyltransferase increased	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Investigations N-terminal prohormone brain natriuretic peptide increased	11.8% 4/34 • Number of events 4 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	8.8% 3/34 • Number of events 3 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	8.8% 3/34 • Number of events 3 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Metabolism and nutrition disorders Hyperkalaemia	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Nervous system disorders Headache	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Psychiatric disorders Insomnia	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Vascular disorders Brachiocephalic arteriosclerosis	17.6% 6/34 • Number of events 6 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	17.6% 6/34 • Number of events 6 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	23.5% 8/34 • Number of events 8 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Vascular disorders Hypertension	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	2.9% 1/34 • Number of events 1 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).
Vascular disorders Hypotension	5.9% 2/34 • Number of events 2 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).	0.00% 0/34 • 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".) Safety set included all randomized subjects, who received the study products (RPH-104 or placebo). This population was used for the safety analysis. The tables below show: * Treatment-emergent adverse events (TEAEs) - AEs that started at or after the time of application of randomized treatment; * Pre-treatment adverse events - AEs that started between the date of signing the ICF by the patient and the time of application of randomized treatment (before receiving any of target treatments).

Additional Information

Sergey Grishin, Director, Dep. of Clinical Development and Medical Expertise in Autoimmune Diseases

R-Pharm

Phone: 0074959567937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any study related information could be made public available only after Sponsors written permission.
Publication restrictions are in place

Restriction type: OTHER