Trial Outcomes & Findings for Study of the Efficacy and Safety of a Single Administration of Olokizumab and RPH-104 With Standard Therapy in Patients With Severe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection (COVID-19) (NCT NCT04380519)

NCT ID: NCT04380519

Last Updated: 2022-01-24

Results Overview

Proportion of patients, responded to the study therapy, in each of the treatment groups. A responder is a patient who has not received tocilizumab or sarilumab and who has a clinical status improvement of ≥1 point on the 6-point COVID-19 scale (where 1 is the most favorable outcome and 6 is the most undesirable outcome) 15 days after the administration of the study drug: 1. Not hospitalized, no activity limitations. 2. Not hospitalized, limited activity. 3. Hospitalized, not requiring supplemental oxygen. 4. Hospitalized, supplemental oxygen with independent breathing. 5. Hospitalized; mechanical ventilation (invasive/non-invasive) or Extracorporeal membrane oxygenation (ECMO). 6. Death.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 372 participants
• Primary outcome timeframe: Day 15
• Results posted on: 2022-01-24

Participant Flow

Enrollment was conducted at 16 clinical sites in Russian Federation. 381 subjects were screened and 372 subjects were enrolled (randomized). A total of 371 subjects were treated, and 336 subjects completed the study. A total of 372 subjects were analyzed for efficacy in the Intent-to-Treat (ITT) Population, 352 subjects in the modified ITT Population (mITT) and 371 subjects were analyzed for safety in the Safety Population.

Participant milestones

Measure	RPH -104 80 mg Subcutaneous single injection of RPH-104 80 mg (2 ml 40 mg/mL solution) on Day 1, in addition to standard therapy.	Olokizumab 64 mg Subcutaneous single injection of Olokizumab 64 mg (0,4 ml 160 mg/mL solution) on Day 1, in addition to standard therapy.	Placebo Subcutaneous single injection of 2 ml solution of Placebo (Normal Saline) on Day 1, in addition to standard therapy.
Overall Study STARTED	124	124	124
Overall Study Intent-to-Treat (ITT)	124	124	124
Overall Study Modified Intent-to-Treat (mITT)	115	119	118
Overall Study Safety Population	123	124	124
Overall Study COMPLETED	106	113	117
Overall Study NOT COMPLETED	18	11	7

Reasons for withdrawal

Measure	RPH -104 80 mg Subcutaneous single injection of RPH-104 80 mg (2 ml 40 mg/mL solution) on Day 1, in addition to standard therapy.	Olokizumab 64 mg Subcutaneous single injection of Olokizumab 64 mg (0,4 ml 160 mg/mL solution) on Day 1, in addition to standard therapy.	Placebo Subcutaneous single injection of 2 ml solution of Placebo (Normal Saline) on Day 1, in addition to standard therapy.
Overall Study Withdrawal by Subject	4	0	1
Overall Study Death	14	9	6
Overall Study Adverse Event	0	1	0
Overall Study relatives' decision	0	1	0

Baseline Characteristics

Study of the Efficacy and Safety of a Single Administration of Olokizumab and RPH-104 With Standard Therapy in Patients With Severe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection (COVID-19)

Baseline characteristics by cohort

Measure	RPH -104 80 mg n=124 Participants Subcutaneous single injection of RPH-104 80 mg (2 ml 40 mg/mL solution) on Day 1, in addition to standard therapy.	Olokizumab 64 mg n=124 Participants Subcutaneous single injection of Olokizumab 64 mg (0,4 ml 160 mg/mL solution) on Day 1, in addition to standard therapy.	Placebo n=124 Participants Subcutaneous single injection of 2 ml solution of Placebo (Normal Saline) on Day 1, in addition to standard therapy.	Total n=372 Participants Total of all reporting groups
Age, Continuous	58.0 years n=5 Participants	59.6 years n=7 Participants	59.7 years n=5 Participants	59.1 years n=4 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	58 Participants n=7 Participants	57 Participants n=5 Participants	176 Participants n=4 Participants
Sex: Female, Male Male	63 Participants n=5 Participants	66 Participants n=7 Participants	67 Participants n=5 Participants	196 Participants n=4 Participants
Race/Ethnicity, Customized White	124 Participants n=5 Participants	123 Participants n=7 Participants	124 Participants n=5 Participants	371 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	123 Participants n=5 Participants	123 Participants n=7 Participants	124 Participants n=5 Participants	370 Participants n=4 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 15

Population: The intent-to-treat (ITT) population included all randomized patients.

Proportion of patients, responded to the study therapy, in each of the treatment groups.

A responder is a patient who has not received tocilizumab or sarilumab and who has a clinical status improvement of ≥1 point on the 6-point COVID-19 scale (where 1 is the most favorable outcome and 6 is the most undesirable outcome) 15 days after the administration of the study drug:

1. Not hospitalized, no activity limitations.

2. Not hospitalized, limited activity.

3. Hospitalized, not requiring supplemental oxygen.

4. Hospitalized, supplemental oxygen with independent breathing.

5. Hospitalized; mechanical ventilation (invasive/non-invasive) or Extracorporeal membrane oxygenation (ECMO).

6. Death.

Outcome measures

Measure	RPH -104 80 mg n=124 Participants Subcutaneous single injection of RPH-104 80 mg (2 ml 40 mg/mL solution) on Day 1, in addition to standard therapy.	Olokizumab 64 mg n=124 Participants Subcutaneous single injection of Olokizumab 64 mg (0,4 ml 160 mg/mL solution) on Day 1, in addition to standard therapy.	Placebo n=124 Participants Subcutaneous single injection of 2 ml solution of Placebo (Normal Saline) on Day 1, in addition to standard therapy.
Proportion of Responders in Each Treatment Group	88 Participants	98 Participants	87 Participants

SECONDARY outcome

Timeframe: from Day 2 until Day 15, Day 29

Population: The ITT population was the primary analysis population.

Changes of patients' clinical status on a 6 points ordinal scale (where 1 was the most favorable outcome and 6 was the most undesirable outcome) over time.

The 6-point ordinal scale included the following categories:

1. Not hospitalized, no activity limitations.

2. Not hospitalized, limited activity.

3. Hospitalized, not requiring supplemental oxygen.

4. Hospitalized, supplemental oxygen, with independent breathing.

5. Hospitalized, mechanical ventilation (invasive/non-invasive) or ECMO.

6. Death.

Outcome measures

Measure	RPH -104 80 mg n=124 Participants Subcutaneous single injection of RPH-104 80 mg (2 ml 40 mg/mL solution) on Day 1, in addition to standard therapy.	Olokizumab 64 mg n=124 Participants Subcutaneous single injection of Olokizumab 64 mg (0,4 ml 160 mg/mL solution) on Day 1, in addition to standard therapy.	Placebo n=124 Participants Subcutaneous single injection of 2 ml solution of Placebo (Normal Saline) on Day 1, in addition to standard therapy.
Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale Day 29 · without change	1 Participants	0 Participants	1 Participants
Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale Day 15 · improvement	88 Participants	99 Participants	96 Participants
Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale Day 15 · worsening (including deaths)	13 Participants	8 Participants	7 Participants
Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale Day 15 · without change	15 Participants	11 Participants	17 Participants
Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale Day 15 · no data	8 Participants	6 Participants	4 Participants
Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale Day 29 · improvement	105 Participants	113 Participants	111 Participants
Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale Day 29 · worsening (including deaths)	14 Participants	9 Participants	8 Participants
Change Over Time in the Clinical Status of Patients Using a 6-point Ordinal Scale Day 29 · no data	4 Participants	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Day 29

Population: The ITT population was the primary analysis population.

The proportion of patients with an improvement in clinical status by 2 or more points on the 6-point ordinal scale (where 1 was the most favorable outcome and 6 was the most undesirable outcome) during the study with no use of tocilizumab or sarilumab.

The 6-point ordinal scale included the following categories:

1. Not hospitalized, no activity limitations.

2. Not hospitalized, limited activity.

3. Hospitalized, not requiring supplemental oxygen.

4. Hospitalized, supplemental oxygen, with independent breathing.

5. Hospitalized, mechanical ventilation (invasive/non-invasive) or ECMO.

6. Death.

Outcome measures

Measure	RPH -104 80 mg n=124 Participants Subcutaneous single injection of RPH-104 80 mg (2 ml 40 mg/mL solution) on Day 1, in addition to standard therapy.	Olokizumab 64 mg n=124 Participants Subcutaneous single injection of Olokizumab 64 mg (0,4 ml 160 mg/mL solution) on Day 1, in addition to standard therapy.	Placebo n=124 Participants Subcutaneous single injection of 2 ml solution of Placebo (Normal Saline) on Day 1, in addition to standard therapy.
The Proportion of Patients With an Improvement in Clinical Status by 2 or More Points on the 6-point Ordinal Scale During the Study With no Use of Tocilizumab or Sarilumab	94 Participants	103 Participants	94 Participants

SECONDARY outcome

Timeframe: from Day 2 until the Day 29

Population: The ITT population was the primary analysis population.

The proportion of patients who received tocilizumab or sarilumab for COVID-19 during the study

Outcome measures

Measure	RPH -104 80 mg n=124 Participants Subcutaneous single injection of RPH-104 80 mg (2 ml 40 mg/mL solution) on Day 1, in addition to standard therapy.	Olokizumab 64 mg n=124 Participants Subcutaneous single injection of Olokizumab 64 mg (0,4 ml 160 mg/mL solution) on Day 1, in addition to standard therapy.	Placebo n=124 Participants Subcutaneous single injection of 2 ml solution of Placebo (Normal Saline) on Day 1, in addition to standard therapy.
The Proportion of Patients Who Received Tocilizumab or Sarilumab for COVID-19 During the Study	10 Participants	5 Participants	15 Participants

SECONDARY outcome

Timeframe: from Day 1 until Day 29

Population: The safety population included all patients who received the IP (371 patients: 124 patients in the OKZ group, 123/124 (99.2%) patients in the RPH-104 group (1 patient did not received the IP) and 124 patients in the Placebo group).

Mortality rate over the follow-up period of the study

Outcome measures

Measure	RPH -104 80 mg n=123 Participants Subcutaneous single injection of RPH-104 80 mg (2 ml 40 mg/mL solution) on Day 1, in addition to standard therapy.	Olokizumab 64 mg n=124 Participants Subcutaneous single injection of Olokizumab 64 mg (0,4 ml 160 mg/mL solution) on Day 1, in addition to standard therapy.	Placebo n=124 Participants Subcutaneous single injection of 2 ml solution of Placebo (Normal Saline) on Day 1, in addition to standard therapy.
Mortality Rate During the Study	14 Participants	9 Participants	6 Participants

Adverse Events

RPH -104 80 mg

Serious events: 15 serious events

Other events: 30 other events

Deaths: 14 deaths

Olokizumab 64 mg

Serious events: 10 serious events

Other events: 23 other events

Deaths: 9 deaths

Placebo

Serious events: 8 serious events

Other events: 35 other events

Deaths: 6 deaths

Serious adverse events

Measure	RPH -104 80 mg n=123 participants at risk Subject randomized to receive subcutaneous single injection of 2 ml solution of RPH-104 on Day 1, in addition to standard therapy RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL glass vial	Olokizumab 64 mg n=124 participants at risk Subject randomized to receive subcutaneous single injection of 0,4 ml solution of Olokizumab on Day 1, in addition to standard therapy Olokizumab 64 mg: solution for subcutaneous administration 160 mg/mL, in the 2-mL glass vial (target volume 0,4 ml)	Placebo n=124 participants at risk Subject randomized to receive subcutaneous single injection of 2 ml solution of Placebo on Day 1, in addition to standard therapy Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), in the market package
Cardiac disorders Atrial fibrillation	0.81% 1/123 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Cardiac disorders Cardiac failure acute	1.6% 2/123 • Number of events 2 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Cardiac disorders Pericardial effusion	0.00% 0/123 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.81% 1/124 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Cardiac disorders Ventricular fibrillation	0.00% 0/123 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.81% 1/124 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Infections and infestations COVID-19	0.81% 1/123 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.81% 1/124 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.81% 1/124 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Infections and infestations Sepsis	2.4% 3/123 • Number of events 3 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	1.6% 2/124 • Number of events 2 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	2.4% 3/124 • Number of events 3 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Infections and infestations Septic shock	1.6% 2/123 • Number of events 2 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.81% 1/124 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Infections and infestations Viral sepsis	0.81% 1/123 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/123 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	1.6% 2/124 • Number of events 2 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Nervous system disorders Cerebral infarction	0.81% 1/123 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Nervous system disorders Cerebral ischemia	0.81% 1/123 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.6% 2/123 • Number of events 2 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	1.6% 2/124 • Number of events 2 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.81% 1/124 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	0.81% 1/123 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.81% 1/123 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	2.4% 3/124 • Number of events 3 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.81% 1/123 • Number of events 1 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	0.00% 0/124 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.

Other adverse events

Measure	RPH -104 80 mg n=123 participants at risk Subject randomized to receive subcutaneous single injection of 2 ml solution of RPH-104 on Day 1, in addition to standard therapy RPH-104 80 mg: solution for subcutaneous administration 40 mg/mL, 2 mL in the 4-mL glass vial	Olokizumab 64 mg n=124 participants at risk Subject randomized to receive subcutaneous single injection of 0,4 ml solution of Olokizumab on Day 1, in addition to standard therapy Olokizumab 64 mg: solution for subcutaneous administration 160 mg/mL, in the 2-mL glass vial (target volume 0,4 ml)	Placebo n=124 participants at risk Subject randomized to receive subcutaneous single injection of 2 ml solution of Placebo on Day 1, in addition to standard therapy Placebo: Normal Saline (0.9% Sodium Chloride solution for Injection), in the market package
Investigations Alanine aminotransferase increased	10.6% 13/123 • Number of events 13 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	8.9% 11/124 • Number of events 11 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	12.1% 15/124 • Number of events 15 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Investigations Aspartate aminotransferase increased	9.8% 12/123 • Number of events 12 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	7.3% 9/124 • Number of events 9 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	9.7% 12/124 • Number of events 12 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.
Investigations Gamma-glutamyltransferase increased	4.1% 5/123 • Number of events 5 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	2.4% 3/124 • Number of events 3 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.	6.5% 8/124 • Number of events 8 • All Adverse Events (AEs), except serious ones, were recorded from the moment of the use of the IP. AEs recorded prior to the start of the study therapy, but after the patient was included in the study, were recorded in the electronic CRF Case report form (eCRF) as "Concomitant diseases". AEs were registered until the end of the follow-up period (day 29). All AE analyses were performed in the safety population. (The safety population included all patients who received the IP.) No statistical comparisons were conducted on the AE data. Data for treatment-emergent AEs (TEAEs) were reported below. TEAE is an AE that started at or after the time of administration of the randomized IP.

Additional Information

Sergey Grishin, Head of Scientific Affairs Department

R-Pharm

Phone: 0074959567937

Email: sa.grishin@rpharm.ru

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