Trial Outcomes & Findings for Evaluation of the Efficacy and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo and Adalimumab, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Have Active Disease (NCT NCT02760407)

Last Updated: 2023-09-21

Results Overview

The difference between OKZ and placebo in the percentage of subjects achieving an ACR20 response and remaining on randomized treatment and in the study at Week 12. (where a responder was defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12) This endpoint served to demonstrate that the efficacy of OKZ was superior to placebo. American College of Rheumatology 20 % response is a composite defined as a ≥ 20% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count 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 (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1648 participants

Primary outcome timeframe

at Week 12

Results posted on

2023-09-21

Participant Flow

Enrollment was conducted at 208 clinical sites across 18 countries (US,EU,UK, Russian Federation, Asia, Latin America). 3359 subjects were screened and 1648 subjects were enrolled (randomized). A total of 1645 subjects were treated, and 1483 subjects completed the study. A total of 1648 subjects were analyzed for efficacy in the ITT Population and 1645 subjects were analyzed for safety in the Safety Population.

Participant milestones

Participant milestones
Measure	Arm 1: Olokizumab q4w + Methotrexate Olokizumab 64mg subcutaneous q4w + placebo + Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator +concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)
Overall Study STARTED	479	464	462	243
Overall Study COMPLETED	443	421	412	207
Overall Study NOT COMPLETED	36	43	50	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: Olokizumab q4w + Methotrexate Olokizumab 64mg subcutaneous q4w + placebo + Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator +concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)
Overall Study Death	2	3	1	1
Overall Study Lost to Follow-up	1	7	4	6
Overall Study Withdrawal by Subject	25	31	37	25
Overall Study Violation of Eligibility criteria	0	0	1	1
Overall Study Personal reasons	0	0	0	1
Overall Study The subject was early discontinued due to lab Adverse Event as per Investigator's decision	1	0	0	0
Overall Study Use of prohibited Medication	0	0	1	0
Overall Study Subject didn't Completed Visits Schedule After Serious Adverse Event	0	0	1	0
Overall Study Positive Quantiferon Testing, Patient Was Not Taken Prophylactic Medication	1	0	0	0
Overall Study Investigator's Decision (Adverse Event)	0	1	0	0
Overall Study Inadequately Enrolled	0	0	0	1
Overall Study Withdrawal By PI's Decision	0	1	0	0
Overall Study Subject Did not attend treatment period visits due to misunderstanding of protocol	1	0	1	0
Overall Study Subject met permanent IP discontinuation criteria, did not agree for treatment period visits	0	0	1	0
Overall Study Investigator recorded as Sponsor's decision - decreased lymphocyte level	1	0	0	0
Overall Study Study Treatment Was Terminated At The Site	0	0	1	0
Overall Study Subject Taken Out Of Study Due To Sponsor Investigating Investigational Product.	1	0	0	0
Overall Study Inadequately enrolled patient refused to Follow-Up	1	0	0	0
Overall Study Lack Of Efficacy Per PI	0	0	0	1
Overall Study Patient had an upper respiratory infection and took medication that was not allowed	1	0	0	0
Overall Study Investigator recorded as Adverse Event	1	0	2	0

Baseline Characteristics

Evaluation of the Efficacy and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo and Adalimumab, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Have Active Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Olokizumab q4w + Methotrexate n=479 Participants Olokizumab 64mg subcutaneous q4w+ placebo+Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.)+concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 2: Olokizumab q2w + Methotrexate n=464 Participants Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 3: Adalimumab q2w + Methotrexate n=462 Participants Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate n=243 Participants Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Total n=1648 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	389 Participants n=93 Participants	379 Participants n=4 Participants	367 Participants n=27 Participants	192 Participants n=483 Participants	1327 Participants n=36 Participants
Age, Categorical >=65 years	90 Participants n=93 Participants	85 Participants n=4 Participants	95 Participants n=27 Participants	51 Participants n=483 Participants	321 Participants n=36 Participants
Age, Continuous	53.7 years STANDARD_DEVIATION 12.09 • n=93 Participants	53.3 years STANDARD_DEVIATION 11.92 • n=4 Participants	54.3 years STANDARD_DEVIATION 12.32 • n=27 Participants	54.7 years STANDARD_DEVIATION 11.85 • n=483 Participants	53.9 years STANDARD_DEVIATION 12.07 • n=36 Participants
Sex: Female, Male Female	378 Participants n=93 Participants	352 Participants n=4 Participants	363 Participants n=27 Participants	190 Participants n=483 Participants	1283 Participants n=36 Participants
Sex: Female, Male Male	101 Participants n=93 Participants	112 Participants n=4 Participants	99 Participants n=27 Participants	53 Participants n=483 Participants	365 Participants n=36 Participants
Race/Ethnicity, Customized Asian	6 Participants n=93 Participants	10 Participants n=4 Participants	4 Participants n=27 Participants	5 Participants n=483 Participants	25 Participants n=36 Participants
Race/Ethnicity, Customized Black or African American	15 Participants n=93 Participants	20 Participants n=4 Participants	23 Participants n=27 Participants	11 Participants n=483 Participants	69 Participants n=36 Participants
Race/Ethnicity, Customized White	406 Participants n=93 Participants	382 Participants n=4 Participants	385 Participants n=27 Participants	203 Participants n=483 Participants	1376 Participants n=36 Participants
Race/Ethnicity, Customized Other/Mixed	52 Participants n=93 Participants	52 Participants n=4 Participants	50 Participants n=27 Participants	24 Participants n=483 Participants	178 Participants n=36 Participants
Region of Enrollment Colombia	18 participants n=93 Participants	17 participants n=4 Participants	16 participants n=27 Participants	8 participants n=483 Participants	59 participants n=36 Participants
Region of Enrollment Argentina	44 participants n=93 Participants	42 participants n=4 Participants	43 participants n=27 Participants	24 participants n=483 Participants	153 participants n=36 Participants
Region of Enrollment Romania	0 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants
Region of Enrollment Hungary	15 participants n=93 Participants	13 participants n=4 Participants	13 participants n=27 Participants	10 participants n=483 Participants	51 participants n=36 Participants
Region of Enrollment United States	75 participants n=93 Participants	71 participants n=4 Participants	72 participants n=27 Participants	39 participants n=483 Participants	257 participants n=36 Participants
Region of Enrollment Czechia	58 participants n=93 Participants	50 participants n=4 Participants	51 participants n=27 Participants	30 participants n=483 Participants	189 participants n=36 Participants
Region of Enrollment United Kingdom	3 participants n=93 Participants	1 participants n=4 Participants	6 participants n=27 Participants	1 participants n=483 Participants	11 participants n=36 Participants
Region of Enrollment Russia	20 participants n=93 Participants	21 participants n=4 Participants	25 participants n=27 Participants	11 participants n=483 Participants	77 participants n=36 Participants
Region of Enrollment Latvia	1 participants n=93 Participants	3 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	4 participants n=36 Participants
Region of Enrollment South Korea	2 participants n=93 Participants	4 participants n=4 Participants	1 participants n=27 Participants	4 participants n=483 Participants	11 participants n=36 Participants
Region of Enrollment Taiwan	2 participants n=93 Participants	3 participants n=4 Participants	2 participants n=27 Participants	1 participants n=483 Participants	8 participants n=36 Participants
Region of Enrollment Brazil	33 participants n=93 Participants	33 participants n=4 Participants	30 participants n=27 Participants	16 participants n=483 Participants	112 participants n=36 Participants
Region of Enrollment Poland	90 participants n=93 Participants	85 participants n=4 Participants	87 participants n=27 Participants	46 participants n=483 Participants	308 participants n=36 Participants
Region of Enrollment Mexico	63 participants n=93 Participants	63 participants n=4 Participants	59 participants n=27 Participants	30 participants n=483 Participants	215 participants n=36 Participants
Region of Enrollment Bulgaria	18 participants n=93 Participants	20 participants n=4 Participants	19 participants n=27 Participants	8 participants n=483 Participants	65 participants n=36 Participants
Region of Enrollment Lithuania	22 participants n=93 Participants	22 participants n=4 Participants	22 participants n=27 Participants	8 participants n=483 Participants	74 participants n=36 Participants
Region of Enrollment Germany	11 participants n=93 Participants	13 participants n=4 Participants	10 participants n=27 Participants	6 participants n=483 Participants	40 participants n=36 Participants
Region of Enrollment Estonia	4 participants n=93 Participants	3 participants n=4 Participants	5 participants n=27 Participants	1 participants n=483 Participants	13 participants n=36 Participants
Body Mass Index (BMI)	28.654 kg/m^2 n=93 Participants	28.656 kg/m^2 n=4 Participants	28.532 kg/m^2 n=27 Participants	28.573 kg/m^2 n=483 Participants	28.609 kg/m^2 n=36 Participants

PRIMARY outcome

Timeframe: at Week 12

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=479 Participants Olokizumab 64mg subcutaneous q4w+ placebo+Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate n=464 Participants Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate n=462 Participants Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate n=243 Participants Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response	342 Participants	326 Participants	309 Participants	108 Participants

SECONDARY outcome

Timeframe: at Week 12

A responder was defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12.This endpoint served to demonstrate that the efficacy of OKZ was non-inferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) was demonstrated concurrently based on the same endpoint. American College of Rheumatology 20 % response is a composite defined as a ≥ 20% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count 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 (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP)

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=479 Participants Olokizumab 64mg subcutaneous q4w+ placebo+Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate n=464 Participants Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate n=462 Participants Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate n=243 Participants Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
Percentage of Subjects Achieving ACR20 Response: Olokizumab Comparison With Adalimumab	342 Participants	326 Participants	309 Participants	108 Participants

SECONDARY outcome

Timeframe: at Week 12

Defined as Disease Activity Score 28-joint count (DAS28) C-reactive protein (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=479 Participants Olokizumab 64mg subcutaneous q4w+ placebo+Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate n=464 Participants Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate n=462 Participants Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate n=243 Participants Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
Percentage of Subjects Achieving Low Disease Activity	220 Participants	210 Participants	177 Participants	31 Participants

SECONDARY outcome

Timeframe: at Week 12

Percentage of subjects achieving low disease activity, defined as DAS28 (CRP) \<3.2, and remaining on randomized treatment and in the study at Week 12; served to demonstrate that the efficacy of OKZ was noninferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) was demonstrated concurrently based on the same endpoint

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=479 Participants Olokizumab 64mg subcutaneous q4w+ placebo+Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate n=464 Participants Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate n=462 Participants Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate n=243 Participants Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
Percentage of Subjects Achieving Low Disease Activity: Olokizumab Comparison With Adalimumab	220 Participants	210 Participants	177 Participants	31 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 assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions.The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3 where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question. A decrease from baseline indicates improvement for HAQ-DI.The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. The HAQ-DI total score ranges from 0 (the best outcome) to 3 (the worst outcome).

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=473 Participants Olokizumab 64mg subcutaneous q4w+ placebo+Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate n=449 Participants Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate n=456 Participants Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate n=235 Participants Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose 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)	-0.60 score on a scale Standard Error 0.028	-0.65 score on a scale Standard Error 0.030	-0.61 score on a scale Standard Error 0.029	-0.42 score on a scale Standard Error 0.039

SECONDARY outcome

Timeframe: at Week 24

Difference between OKZ and placebo in the percentage of subjects achieving an ACR50 response and remaining on randomized treatment and in the study at Week 24 American College of Rheumatology 50% Response is a composite defined as ≥50%, improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count 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 (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP)

Outcome measures

Outcome measures
Measure	Arm 1: Olokizumab q4w + Methotrexate n=479 Participants Olokizumab 64mg subcutaneous q4w+ placebo+Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate n=464 Participants Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate n=462 Participants Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate n=243 Participants Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response	240 Participants	234 Participants	214 Participants	55 Participants

SECONDARY outcome

Timeframe: at Week 24

Difference between OKZ and placebo in the 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=479 Participants Olokizumab 64mg subcutaneous q4w+ placebo+Methotrexate 64 mg Olokizumab administered subcutaneously once every 4 weeks + placebo in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.) + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate n=464 Participants Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate n=462 Participants Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)	Arm 4: Placebo q2w + Methotrexate n=243 Participants Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 (Remission)	58 Participants	51 Participants	60 Participants	10 Participants

Adverse Events

Arm 1: Olokizumab q4w + Methotrexate

Serious events: 20 serious events

Other events: 177 other events

Deaths: 2 deaths

Arm 2: Olokizumab q2w + Methotrexate

Serious events: 22 serious events

Other events: 183 other events

Deaths: 3 deaths

Arm 3: Adalimumab q2w + Methotrexate

Serious events: 26 serious events

Other events: 129 other events

Deaths: 1 deaths

Arm 4: Placebo q2w + Methotrexate

Serious events: 12 serious events

Other events: 71 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm 1: Olokizumab q4w + Methotrexate n=477 participants at risk Olokizumab 64mg subcutaneous q4w+ placebo+Methotrexate 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 with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 2: Olokizumab q2w + Methotrexate n=463 participants at risk Olokizumab 64mg subcutaneous q2w + Methotrexate 64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 3: Adalimumab q2w + Methotrexate n=462 participants at risk Active Comparator, Adalimumab 40mg q2w subcutaneous + Methotrexate Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).	Arm 4: Placebo q2w + Methotrexate n=243 participants at risk Placebo subcutaneous q2w + Methotrexate Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular).
Infections and infestations Nasopharyngitis	5.5% 26/477 • Number of events 34 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	6.3% 29/463 • Number of events 35 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	6.3% 29/462 • Number of events 32 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	7.4% 18/243 • Number of events 23 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Infections and infestations Upper respiratory tract infection	6.1% 29/477 • Number of events 33 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	6.0% 28/463 • Number of events 31 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	5.6% 26/462 • Number of events 30 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	6.6% 16/243 • Number of events 17 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Infections and infestations Urinary tract infection	2.9% 14/477 • Number of events 14 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	1.5% 7/463 • Number of events 9 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	4.1% 19/462 • Number of events 20 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	3.7% 9/243 • Number of events 10 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Infections and infestations Bronchitis	2.1% 10/477 • Number of events 10 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	2.6% 12/463 • Number of events 12 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	2.4% 11/462 • Number of events 13 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	4.5% 11/243 • Number of events 11 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Metabolism and nutrition disorders Hypercholesterolaemia	4.2% 20/477 • Number of events 20 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	6.3% 29/463 • Number of events 29 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	1.3% 6/462 • Number of events 6 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	1.2% 3/243 • Number of events 3 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Metabolism and nutrition disorders Dyslipidaemia	3.1% 15/477 • Number of events 15 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	5.4% 25/463 • Number of events 28 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	0.87% 4/462 • Number of events 4 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	1.6% 4/243 • Number of events 4 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Metabolism and nutrition disorders Hyperlipidaemia	2.1% 10/477 • Number of events 10 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	4.8% 22/463 • Number of events 24 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	1.1% 5/462 • Number of events 6 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	0.82% 2/243 • Number of events 2 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Investigations Alanine aminotransferase increased	11.1% 53/477 • Number of events 88 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	8.9% 41/463 • Number of events 70 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	1.9% 9/462 • Number of events 20 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	1.6% 4/243 • Number of events 8 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Investigations Aspartate aminotransferase increased	5.0% 24/477 • Number of events 38 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	5.0% 23/463 • Number of events 27 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	1.7% 8/462 • Number of events 15 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	0.82% 2/243 • Number of events 2 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Vascular disorders Hypertension	5.7% 27/477 • Number of events 31 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	5.4% 25/463 • Number of events 26 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	2.8% 13/462 • Number of events 13 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	3.3% 8/243 • Number of events 8 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
Nervous system disorders Headache	2.3% 11/477 • Number of events 12 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	2.2% 10/463 • Number of events 11 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	3.0% 14/462 • Number of events 17 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	4.9% 12/243 • Number of events 12 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment
General disorders Injection site erythema	1.7% 8/477 • Number of events 8 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	1.7% 8/463 • Number of events 12 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	4.3% 20/462 • Number of events 51 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of study treatment	0.82% 2/243 • Number of events 2 • All AEs 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, up to approximately 44 weeks. 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 started or worsened after the first dose of 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