Trial Outcomes & Findings for Evaluation of the Effectiveness and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Have Active Disease (NCT NCT02760368)

Last Updated: 2023-09-21

Results Overview

A responder was defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. The calculations were based on a ≥ 20% improvement from baseline in the swollen joint count (SJC) assessed in 66 joints and in the tender joint count (TJC) assessed in 68 joints; and a ≥ 20% improvement from baseline in at least 3 of the 5 remaining core set measures: Patient Global Assessment of Disease Activity (Visual Analog Scale (VAS) assessment), Patient Assessment of Pain (VAS assessment), Health Assessment Questionnaire-Disability Index (HAQ-DI), Physician Global Assessment (VAS assessment), Level of acute phase reactant (CRP or ESR, using level of CRP in this study).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

428 participants

Primary outcome timeframe

at Week 12

Results posted on

2023-09-21

Participant Flow

Enrollment was conducted at 42 clinical sites (in Belarus, Bulgaria, Russia,Turkey) between May 2016 and April 2018. 785 patients were included, 357 patients screen-failed, 428 patients were randomized (143 patients in OKZ q2w +MTX group, 142 patients in OKZ q4w +MTX group, 143 patients in Placebo q2w +MTX group). 1 subject was randomized by mistake and didn't receive the study treatment. The primary efficacy analysis set included 428 subjects, and the safety analysis set included 427 subjects.

Participant milestones

Participant milestones
Measure	Arm 1: Olokizumab q4w + Methotrexate Olokizumab 64 mg Subcutaneous q4w + placebo + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w will receive placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.)+concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 2: Olokizumab q2w + Methotrexate Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 3: Placebo + Methotrexate Placebo Subcutaneous q2w + Methotrexate (oral) Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)
Overall Study STARTED	142	143	143
Overall Study COMPLETED	134	130	132
Overall Study NOT COMPLETED	8	13	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: Olokizumab q4w + Methotrexate Olokizumab 64 mg Subcutaneous q4w + placebo + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w will receive placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.)+concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 2: Olokizumab q2w + Methotrexate Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 3: Placebo + Methotrexate Placebo Subcutaneous q2w + Methotrexate (oral) Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)
Overall Study Withdrawal by Subject	8	12	9
Overall Study Screen Failure	0	0	1
Overall Study Death	0	1	0
Overall Study Withdrawal by Sponsor	0	0	1

Baseline Characteristics

1 subject had been mistakenly randomized to the placebo group and was discontinued immediately prior to investigational product administration. Therefore, the patient was included in the ITT population by definition, but no other data except baseline demographics (age, gender, race, ethnicity, and region of inclusion) were collected.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Olokizumab q4w + Methotrexate n=142 Participants Olokizumab 64 mg Subcutaneous q4w +placebo q4w+ Methotrexate (oral) Olokizumab q4w: 160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial + placebo (sodium chloride 0.9% solution supplied in polypropylene plastic ampoules of 10 mL cartons to contain 10 ampoules)	Arm 2: Olokizumab q2w + Methotrexate n=143 Participants Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral) Olokizumab q2w: 160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial	Arm 3: Placebo q2w + Methotrexate n=143 Participants Placebo Subcutaneous q2w + Methotrexate (oral) Placebo q2w: sodium chloride 0.9% solution supplied in polypropylene plastic ampoules of 10 mL cartons to contain 10 ampoules	Total n=428 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=142 Participants	0 Participants n=143 Participants	0 Participants n=143 Participants	0 Participants n=428 Participants
Age, Categorical Between 18 and 65 years	129 Participants n=142 Participants	125 Participants n=143 Participants	124 Participants n=143 Participants	378 Participants n=428 Participants
Age, Categorical >=65 years	13 Participants n=142 Participants	18 Participants n=143 Participants	19 Participants n=143 Participants	50 Participants n=428 Participants
Age, Continuous	49.1 years STANDARD_DEVIATION 12.07 • n=142 Participants	52.0 years STANDARD_DEVIATION 11.77 • n=143 Participants	52.7 years STANDARD_DEVIATION 11.29 • n=143 Participants	51.3 years STANDARD_DEVIATION 11.79 • n=428 Participants
Sex: Female, Male Female	118 Participants n=142 Participants	116 Participants n=143 Participants	120 Participants n=143 Participants	354 Participants n=428 Participants
Sex: Female, Male Male	24 Participants n=142 Participants	27 Participants n=143 Participants	23 Participants n=143 Participants	74 Participants n=428 Participants
Race/Ethnicity, Customized participants · Asian	0 Participants n=142 Participants	0 Participants n=143 Participants	1 Participants n=143 Participants	1 Participants n=428 Participants
Race/Ethnicity, Customized participants · Black or African American	0 Participants n=142 Participants	0 Participants n=143 Participants	0 Participants n=143 Participants	0 Participants n=428 Participants
Race/Ethnicity, Customized participants · White	142 Participants n=142 Participants	143 Participants n=143 Participants	142 Participants n=143 Participants	427 Participants n=428 Participants
Race/Ethnicity, Customized participants · Other/Mixed	0 Participants n=142 Participants	0 Participants n=143 Participants	0 Participants n=143 Participants	0 Participants n=428 Participants
Region of Enrollment Bulgaria	6 participants n=142 Participants	12 participants n=143 Participants	9 participants n=143 Participants	27 participants n=428 Participants
Region of Enrollment Russia	129 participants n=142 Participants	124 participants n=143 Participants	128 participants n=143 Participants	381 participants n=428 Participants
Region of Enrollment Belarus	7 participants n=142 Participants	7 participants n=143 Participants	6 participants n=143 Participants	20 participants n=428 Participants
Body Mass Index (BMI)	26.40 kg/m^2 n=142 Participants • 1 subject had been mistakenly randomized to the placebo group and was discontinued immediately prior to investigational product administration. Therefore, the patient was included in the ITT population by definition, but no other data except baseline demographics (age, gender, race, ethnicity, and region of inclusion) were collected.	26.62 kg/m^2 n=143 Participants • 1 subject had been mistakenly randomized to the placebo group and was discontinued immediately prior to investigational product administration. Therefore, the patient was included in the ITT population by definition, but no other data except baseline demographics (age, gender, race, ethnicity, and region of inclusion) were collected.	26.93 kg/m^2 n=142 Participants • 1 subject had been mistakenly randomized to the placebo group and was discontinued immediately prior to investigational product administration. Therefore, the patient was included in the ITT population by definition, but no other data except baseline demographics (age, gender, race, ethnicity, and region of inclusion) were collected.	26.65 kg/m^2 n=427 Participants • 1 subject had been mistakenly randomized to the placebo group and was discontinued immediately prior to investigational product administration. Therefore, the patient was included in the ITT population by definition, but no other data except baseline demographics (age, gender, race, ethnicity, and region of inclusion) were collected.
Baseline Disease Severity Inactive (DAS28 (CRP) ≤ 3.2)	0 Participants n=142 Participants	0 Participants n=143 Participants	0 Participants n=143 Participants	0 Participants n=428 Participants
Baseline Disease Severity Moderately Active (DAS28 (CRP) > 3.2 to ≤ 5.1)	21 Participants n=142 Participants	18 Participants n=143 Participants	22 Participants n=143 Participants	61 Participants n=428 Participants
Baseline Disease Severity Very Active (DAS28 (CRP) > 5.1)	121 Participants n=142 Participants	123 Participants n=143 Participants	119 Participants n=143 Participants	363 Participants n=428 Participants

PRIMARY outcome

Timeframe: at Week 12

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=142 Participants Olokizumab 64 mg Subcutaneous q4w + Placebo + Methotrexate (oral) Olokizumab 64 mg subcutaneous once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w will receive placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 2: Olokizumab q2w + Methotrexate n=143 Participants Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 3: Placebo q2w + Methotrexate n=143 Participants Placebo Subcutaneous q2w + Methotrexate (oral) Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)
Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response	100 Participants	91 Participants	37 Participants

SECONDARY outcome

Timeframe: at Week 12

Defined as Disease Activity Score 28 (DAS28) (CRP) \< 3.2, and remaining on randomized treatment and in the study at Week 12.

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=142 Participants Olokizumab 64 mg Subcutaneous q4w + Placebo + Methotrexate (oral) Olokizumab 64 mg subcutaneous once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w will receive placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 2: Olokizumab q2w + Methotrexate n=143 Participants Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 3: Placebo q2w + Methotrexate n=143 Participants Placebo Subcutaneous q2w + Methotrexate (oral) Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)
Percentage of Subjects Achieving Low Disease Activity	55 Participants	47 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Intent-to-treat (ITT) population: The ITT population includes all randomized subjects. Subjects were analyzed according to the treatment group to which they were randomized. The ITT population is the primary analysis population. Subjects with a missing baseline are not included. Data after treatment discontinuation are Included, Data after discontinuing study are multiply Imputed based on the return to baseline assumption.

Change of physical ability from baseline (the last available assessment prior to the first dose of the study treatment) to week 12, as measured by HAQ-DI. The HAQ-DI total score ranges from 0 (the best outcome) to 3 (the worst outcome).The HAQ-DI assesses the degree of difficulty experienced in 8 domains (dressing and grooming, arising, eating, walking, hygiene, reach, grip, common daily activities) of daily living activities using 20 questions. Each domain consists of 2 or 3 items. For each question the level of difficulty is scored from 0 (without any difficulty, the best outcome) to 3 (unable to do, the worst outcome). Each category is given a score by taking the maximum score of each question. The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. If fewer than 6 categories had responses, no disability score was calculated.

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=142 Participants Olokizumab 64 mg Subcutaneous q4w + Placebo + Methotrexate (oral) Olokizumab 64 mg subcutaneous once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w will receive placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 2: Olokizumab q2w + Methotrexate n=141 Participants Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 3: Placebo q2w + Methotrexate n=140 Participants Placebo Subcutaneous q2w + Methotrexate (oral) Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)
Improvement of Physical Ability From Baseline to Week 12, as Measured by the Health Assessment Questionnaire Disability Index (HAQ-DI)	-0.52 score on a scale Standard Error 0.046	-0.55 score on a scale Standard Error 0.047	-0.23 score on a scale Standard Error 0.044

SECONDARY outcome

Timeframe: at Week 24

A responder was defined as any subject satisfying ACR50 criteria and remaining on randomized treatment and in the study at Week 24. The calculations were based on a ≥ 50% improvement from baseline in the swollen joint count (SJC) assessed in 66 joints and in the tender joint count (TJC) assessed in 68 joints; and a ≥ 50% improvement from baseline in at least 3 of the 5 remaining core set measures: Patient Global Assessment of Disease Activity (Visual Analog Scale (VAS) assessment), Patient Assessment of Pain (VAS assessment), Health Assessment Questionnaire-Disability Index (HAQ-DI), Physician Global Assessment (VAS assessment), Level of acute phase reactant (CRP or ESR, using level of CRP in this study).

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=142 Participants Olokizumab 64 mg Subcutaneous q4w + Placebo + Methotrexate (oral) Olokizumab 64 mg subcutaneous once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w will receive placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 2: Olokizumab q2w + Methotrexate n=143 Participants Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 3: Placebo q2w + Methotrexate n=143 Participants Placebo Subcutaneous q2w + Methotrexate (oral) Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)
Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response	69 Participants	61 Participants	11 Participants

SECONDARY outcome

Timeframe: at Week 24

Percentage of subjects with Clinical Disease Activity Index (CDAI) ≤ 2.8 (remission) and remaining on randomized treatment and in the study at Week 24

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=142 Participants Olokizumab 64 mg Subcutaneous q4w + Placebo + Methotrexate (oral) Olokizumab 64 mg subcutaneous once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w will receive placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 2: Olokizumab q2w + Methotrexate n=143 Participants Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 3: Placebo q2w + Methotrexate n=143 Participants Placebo Subcutaneous q2w + Methotrexate (oral) Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)
Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 (Remission)	11 Participants	12 Participants	0 Participants

Adverse Events

Arm 1: Olokizumab q4w + Methotrexate

Serious events: 8 serious events

Other events: 53 other events

Deaths: 0 deaths

Arm 2: Olokizumab q2w + Methotrexate

Serious events: 8 serious events

Other events: 51 other events

Deaths: 1 deaths

Arm 3: Placebo q2w + Methotrexate

Serious events: 4 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm 1: Olokizumab q4w + Methotrexate n=142 participants at risk Olokizumab 64 mg Subcutaneous q4w + Placebo + Methotrexate (oral) Olokizumab 64 mg Subcutaneous once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w will receive placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 2: Olokizumab q2w + Methotrexate n=143 participants at risk Olokizumab 64 mg Subcutaneous q2w + Methotrexate (oral) 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 3: Placebo q2w + Methotrexate n=142 participants at risk Placebo Subcutaneous q2w + Methotrexate (oral) Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses) with a stable route of administration (oral, subcutaneous, or intramuscular)
Investigations Alanine aminotransferase increased	21.1% 30/142 • Number of events 44 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	17.5% 25/143 • Number of events 32 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	7.7% 11/142 • Number of events 14 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Investigations Aspartate aminotransferase increased	13.4% 19/142 • Number of events 27 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	11.2% 16/143 • Number of events 22 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	7.0% 10/142 • Number of events 12 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Investigations White blood cell count decreased	4.2% 6/142 • Number of events 13 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	4.9% 7/143 • Number of events 9 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	2.8% 4/142 • Number of events 5 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Investigations Neutrophil count decreased	4.9% 7/142 • Number of events 10 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	4.2% 6/143 • Number of events 6 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	2.1% 3/142 • Number of events 4 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Infections and infestations Nasopharyngitis	2.1% 3/142 • Number of events 3 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	2.8% 4/143 • Number of events 4 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	4.2% 6/142 • Number of events 8 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Infections and infestations Upper respiratory tract infection	4.2% 6/142 • Number of events 9 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	1.4% 2/143 • Number of events 2 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	2.8% 4/142 • Number of events 4 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Investigations Blood cholesterol increased	2.8% 4/142 • Number of events 4 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	4.2% 6/143 • Number of events 7 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	2.1% 3/142 • Number of events 3 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Blood and lymphatic system disorders Leukopenia	4.9% 7/142 • Number of events 10 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	5.6% 8/143 • Number of events 10 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	2.8% 4/142 • Number of events 4 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Blood and lymphatic system disorders Neutropenia	6.3% 9/142 • Number of events 11 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	3.5% 5/143 • Number of events 6 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	1.4% 2/142 • Number of events 2 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Blood and lymphatic system disorders Anaemia	2.1% 3/142 • Number of events 3 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	2.8% 4/143 • Number of events 4 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	4.2% 6/142 • Number of events 9 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.
Investigations Gamma-glutamyltransferase increased	4.2% 6/142 • Number of events 9 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	2.1% 3/143 • Number of events 5 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.	2.8% 4/142 • Number of events 5 • All Adverse Events (AE) were collected from the signature of the informed consent form until the last visit of the subject in the study (up to 22 weeks after the final dose of study treatment) regardless of relationship to study treatment. Any SAE with a start date after the Safety Follow-Up Period was not required to be reported unless the Investigator thought that the event might be related to either the study treatment, study treatment administration, or a protocol procedure. All AEs and SAEs reported below are related to the Safety Population (safety population included all subjects who receive at least 1 dose of study treatment). Data for TEAEs were reported below. A Treatment Emergent Adverse Event (TEAE) is defined as an AE that first occurred or worsened in severity after the first dose of the study treatment.

Additional Information

Maria Lemak, Scientific Advisor

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