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CREDO 2: 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

Sponsor
R-Pharm International, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02760407
Collaborator
Quintiles, Inc. (Industry), OCT Clinical Trials (Other)
1,648
Enrollment
245
Locations
4
Arms
41.4
Actual Duration (Months)
6.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to determine how effective and safe the study drug Olokizumab is, in patients with Rheumatoid Arthritis (RA) who are already receiving, but not fully responding to treatment with methotrexate (MTX).

The primary objective of this study was to evaluate the efficacy of OKZ 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) relative to placebo in subjects with moderately to severely active RA inadequately controlled by MTX therapy

The secondary objective was to evaluate the efficacy of OKZ relative to adalimumab in subjects with moderately to severely active RA inadequately controlled by MTX therapy

Condition or Disease Intervention/Treatment Phase
  • Drug: Olokizumab 64mg q4w
  • Drug: Olokizumab 64mg q2w
  • Drug: Adalimumab 40mg q2w
  • Drug: Placebo q2w
 Phase 3

Detailed Description

The goal of this Phase III study was to assess the efficacy, safety and tolerability of OKZ in subjects with moderately to severely active RA who have responded inadequately to MTX. The primary endpoint of the trial was at Week 12. Olokizumab was expected to reduce the disease activity and improve physical function. The study was expected to provide safety information in a large group of subjects over at least a 24 week period.

This study included a 4-week Screening Period, a double-blind Treatment Period from Week 0 to Week 24, and a Safety Follow-Up Period from Week 24 to Week 44. Subjects were assessed for eligibility to enter the study during the 4-week Screening Period. A total of 1575 subjects were planned to be randomly assigned to 1 of 4 treatment groups in a 2:2:2:1 ratio (450, 450, 450, and 225 subjects per group, respectively):

  1. Olokizumab 64 mg q4w: SC injection of OKZ 64 mg q4w (alternating with SC injection of placebo q4w to maintain blinding) + MTX

  2. Olokizumab 64 mg q2w: SC injection of OKZ 64 mg q2w + MTX

  3. Adalimumab 40 mg q2w: SC injection of adalimumab 40 mg q2w + MTX

  4. Placebo: SC injection of placebo q2w + MTX

Throughout the double-blind Treatment Period, all subjects were required to remain on a stable dose of background MTX with a stable route of administration. Concomitant treatment with folic acid was required for all subjects. The last dose of study treatment (OKZ, adalimumab, or placebo) was at Week 22 in all groups.

Following Visit 2 (randomization; Week 0), subjects returned to the study site at least every 2 weeks through Week 24 for response and safety assessments.

At Week 14, subjects who did not improve by at least 20% in both swollen and tender joint counts were classified as nonresponders and were administered sulfasalazine and/or hydroxychloroquine as rescue medication in addition to the assigned treatment.

After completion of the 24-week double-blind Treatment Period, subjects either rolled over into the long-term open-label extension (OLE) study or entered the Safety Follow-Up Period. During the Safety Follow-Up Period, subjects returned for visits +4, +8, and +22 weeks after the last dose of study treatment.

Subjects who discontinued randomized treatment prematurely were required to come for the End of Treatment (EoT) Visit 2 weeks after the last study treatment administration and then continue with the scheduled study visits.

Adverse events (AEs) were assessed throughout the study (starting when the subject signed the informed consent form) and evaluated using the Common Terminology Criteria for Adverse Events Version 4.0. There was ongoing monitoring of safety events, including laboratory findings, by the Sponsor or the Sponsor's designee. In addition, safety was assessed throughout the study by an independent Data Safety Monitoring Board and potential major adverse cardiac events were evaluated by an independent Cardiovascular Adjudication Committee.

The study was conducted at 209 sites across 18 countries globally (in US, European Union (EU),United Kingdom (UK), Russian Federation, Asia, Latin America)

Study Design

Study Type:
Interventional
Actual Enrollment :
1648 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy
Actual Study Start Date :
May 24, 2016
Actual Primary Completion Date :
Aug 2, 2019
Actual Study Completion Date :
Nov 5, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1: Olokizumab q4w

Olokizumab 64 mg subcutaneous q4w +placebo+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular) 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.)

Drug: Olokizumab 64mg q4w
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial, containing a target fill volume of 1.1 mL (for withdrawal of not less than 0.8 mL) or a target fill volume of 0.5 mL (for withdrawal of not less than 0.4 mL)

Drug: Placebo q2w
sodium chloride 0.9% solution supplied in either a 10 mL vial or ampoule, depending on market availability. Each placebo will be packed into a cardboard carton to contain 1 vial or ampoule
Experimental: Arm 2: Olokizumab q2w

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)

Drug: Olokizumab 64mg q2w
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
Active Comparator: Arm 3: Adalimumab q2w

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)

Drug: Adalimumab 40mg q2w
0.4 or 0.8 mL prefilled, single-dose syringe
Other Names:
  • Humira

    		•
    Placebo Comparator: Arm 4: Placebo q2w

    Placebo q2w subcutaneous + 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)

    Drug: Placebo q2w
    sodium chloride 0.9% solution supplied in either a 10 mL vial or ampoule, depending on market availability. Each placebo will be packed into a cardboard carton to contain 1 vial or ampoule

    Outcome Measures

    Primary Outcome Measures

    1. ACR20 Response [at Week 12]

      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 is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12) This endpoint will serve to demonstrate that the efficacy of OKZ is 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)

    Secondary Outcome Measures

    1. ACR20 Response and to Demonstrate That the Efficacy of OKZ is Non-inferior to Adalimumab [at Week 12]

      Where a responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. This endpoint will serve to demonstrate that the efficacy of OKZ is non-inferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) is 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)

    2. Difference Between OKZ and Placebo in the Percentage of Subjects Achieving Low Disease Activity [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

    3. Difference Between Adalimumab and OKZ in Percentage of Subjects Achieving Low Disease Activity, Defined as DAS28 (CRP) <3.2 [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

    4. Improvement of Physical Ability From Baseline to Week 12, as Measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) [Baseline to Week 12]

      Difference between OKZ and placebo in the improvement of physical ability. Improvement of physical ability from baseline 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 to 3, with higher scores indicating greater disability.

    5. ACR50 Response [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)

    6. Clinical Disease Activity Index (CDAI) ≤2.8 (Remission) [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Subjects willing and able to sign informed consent

    • Subjects must have a diagnosis of adult onset RA classified by ACR/EULAR 2010 revised classification criteria for RA for at least 12 weeks prior to Screening. (If the subject was diagnosed according to ACR 1987 criteria previously, the Investigator may classify the subject per ACR 2010 retrospectively, using available source data)

    • Inadequate response to treatment with MTX for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or ≥10 mg/week if intolerant to higher doses) (The dose and means of administering MTX must have been stable for at least 6 weeks prior to Screening.)

    • Subjects must be willing to take folic acid or equivalent throughout the study.

    • Subjects must have moderately to severely active RA disease as defined by all of the following:

    • ≥6 tender joints (68 joint count) at Screening and baseline; and

    • ≥6 swollen joints (66 joint count) at Screening and baseline; and

    • CRP above ULN at Screening based on the central laboratory results

    Exclusion Criteria:

    • Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (e.g., gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus);However, subjects may have secondary Sjogren's syndrome or hypothyroidism.

    • Subjects who are Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care)

    • Prior exposure to any licensed or investigational compound directly or indirectly targeting IL 6 or IL 6R (including tofacitinib or other Janus kinases and spleen tyrosine kinase [SYK] inhibitors)

    • Prior treatment with cell depleting therapies including anti CD20 or investigational agents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19)

    • Prior use of bDMARDs

    • Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to baseline

    • Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline

    • Prior documented history of no response to hydroxychloroquine and sulfasalazine

    • Prior use of cDMARDs (other than MTX) within the following windows prior to baseline (cDMARDs should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA):

    1. 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine, chloroquine, gold, penicillamine, minocycline, or doxycycline

    2. 12 weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to baseline: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours, or activated charcoal at a dosage of 50 grams 4 times daily for at least 24 hours

    3. 24 weeks for cyclophosphamide

    • Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination with live vaccines during the study

    • Participation in any other investigational drug study within 30 days or 5 times the terminal half-life of the investigational drug, whichever is longer, prior to baseline

    • Other treatments for RA (e.g., Prosorba Device/Column) within 6 months prior to baseline

    • Use of intra-articular hyaluronic acid injections within 4 weeks prior to baseline

    • Use of non-steroidal anti-inflammatory drugs (NSAIDs) on unstable dose or switching of NSAIDs within 2 weeks prior to baseline

    • Previous participation in this study (randomized) or another study of OKZ

    • Abnormal laboratory values as defined below:

    1. Creatinine level ≥ 1.5 mg/dL (132 µmol/L) for females or ≥ 2.0 mg/dL (177 µmol/L) for males

    2. ALT or AST level ≥ 1.5× ULN

    3. Platelets <100×109/L (<100,000/mm3)

    4. White blood cell count <3.5×10^9/L

    5. Neutrophil count <2000×106/L (<2000/mm3)

    6. Hemoglobin level ≤ 80 g/L

    7. Glycosylated hemoglobin (HbA1c) level ≥ 8%

    • Subjects with concurrent acute or chronic viral hepatitis B or C infection as detected by blood tests at Screening(e.g., positive for hepatitis B surface antigen [HBsAg], total hepatitis B core antibody [anti-HBc], or hepatitis C virus antibody [HCV Ab])
    1. Subjects who are are positive for hepatitis B surface antibodies (anti-HBs), but negative for HBsAg and anti-HBc, will be eligible

    • Subjects with HIV infection

    • Subjects with:

    1. Suspected or confirmed current active TB disease or a history of active TB disease

    2. Close contact (i.e., sharing the same household or other enclosed environment, such as a social gathering place, workplace, or facility, for extended periods during the day) with an individual with active TB within 1.5 years prior to Screening

    3. History of untreated latent TB infection (LTBI), regardless of IGRA result at Screening

    1. Subjects with a history of untreated LTBI may be re-screened and enrolled if they fulfill all 3 of the following criteria:

    1. Active TB is ruled out by a certified TB specialist or pulmonologist who is familiar with diagnosing and treating TB (as acceptable per local practice);

    2. The subject has completed at least 30 days of LTBI-appropriate prophylaxis prior to baseline with agents recommended as preventative therapy for LTBI according to country-specific/Centers for Disease Control and Prevention (CDC) guidelines (treatment with isoniazid for 6 months is not an appropriate prophylactic regime for this study and it should not be used); and

    3. The subject is willing to complete the entire course of recommended LTBI therapy

    1. Positive interferon-gamma release assay (IGRA) result at Screening. If indeterminate, the IGRA can be repeated once during the Screening Period. If there is a second indeterminate result, the subject will be excluded i. Subjects with a positive IGRA result at Screening may be re-screened and enrolled if they fulfill all 3 of the following criteria

    1. Active TB is ruled out by a certified TB specialist or pulmonologist who is familiar with diagnosing and treating TB (as acceptable per local practice);

    2. The subject has completed at least 30 days of LTBI-appropriate prophylaxis prior to baseline with agents recommended as preventative therapy for LTBI according to country-specific/CDC guidelines (treatment with isoniazid for 6 months is not an appropriate prophylactic regime for this study and it should not be used); and

    3. The subject is willing to complete the entire course of recommended LTBI therapy

    1. If a subject with a positive IGRA result at Screening has documented evidence of completing treatment for LTBI with a treatment regime and treatment duration that are appropriate for this study, the subject may be enrolled without further prophylaxis if recommended by a certified TB specialist or pulmonologist who is familiar with diagnosing and treating TB (as acceptable per local practice) and no new exposure in close contact with an individual with active TB after completing the prophylactic treatment is suspected

    • Concurrent malignancy or a history of malignancy within the last 5 years (with the exception of successfully treated carcinoma of the cervix in situ and successfully treated basal cell carcinoma and squamous cell carcinoma not less than 1 year prior to Screening [and no more than 3 excised skin cancers within the last 5 years prior to Screening])

    • Subjects with any of the following CV conditions:

    1. Uncompensated congestive heart failure, or class III or IV heart failure defined by the New York Heart Association classification (The Criteria Committee of the New York Heart Association, 1994)

    2. Untreated or resistant arterial hypertension Grade II-III (systolic blood pressure (BP) >100 mm Hg)

    3. History or presence of concurrent severe and/or uncontrolled CV disorder (including but not limited to acute coronary syndrome or stroke/transient ischemic attack in the previous 3 months before Screening) that would, in the Investigator's judgment, contraindicate subject participation in the clinical study, or clinically significant enough in the opinion of the Investigator to alter the disposition of the study treatment, or constitute a possible confounding factor for assessment of efficacy or safety of the study treatment

    • Subjects with a history or presence of any concurrent severe and/or uncontrolled medical condition (including but not limited to respiratory, hepatic, renal, GI, endocrinological, dermatological, neurological, psychiatric, hematological (including bleeding disorder), or immunologic/immunodeficiency disorder(s) ) that would, in the Investigator's judgment, contraindicate subject participation in the clinical study, or clinically significant enough in the opinion of the Investigator to alter the disposition of the study treatment, or constitute a possible confounding factor for assessment of efficacy or safety of the study treatment

    • Uncontrolled diabetes mellitus

    • Subjects with any infection requiring oral antibiotic or antiviral therapy in the 2 weeks prior to Screening or at baseline, injectable anti-infective therapy in the last 4 weeks prior to baseline, or serious or recurrent infection with history of hospitalization in the 6 months prior to baseline

    • Subjects with evidence of disseminated herpes zoster infection, zoster encephalitis, meningitis, or other non-self-limited herpes zoster infections in the 6 months prior to baseline

    • Subjects with planned surgery during the study or surgery ≤ 4 weeks prior to Screening and from which the subject has not fully recovered, as judged by the Investigator

    • Subjects with diverticulitis or other symptomatic GI conditions that might predispose the subject to perforations, including subjects with history of such predisposing conditions (e.g., diverticulitis, GI perforation, or ulcerative colitis)

    • Pre-existing central nervous system demyelinating disorders (e.g., multiple sclerosis and optic neuritis)

    • History of chronic alcohol or drug abuse as judged by the Investigator

    • Female subjects who are pregnant, currently lactating, have lactated within the last 12 weeks, or who are planning to become pregnant during the study or within 6 months of last dose of study treatment

    • Female subjects of childbearing potential (unless permanent cessation of menstrual periods, determined retrospectively after a woman has experienced 12 months of natural amenorrhea as defined by the amenorrhea with underlying status (e.g., correlative age) or 6 months of natural amenorrhea with documented serum follicle-stimulating hormone levels >40 mIU/mL and estradiol <20 pg/mL) who are not willing to use a highly effective method of contraception during the study and for at least 6 months after the last administration of study treatment

    OR

    Male subjects with partners of childbearing potential not willing to use a highly effective method of contraception during the study and for at least 3 months after the last administration of study treatment

    Highly effective contraception is defined as:
    1. Female sterilization surgery: hysterectomy, surgical bilateral oophorectomy (with or without hysterectomy), or tubal ligation at least 6 weeks prior to the first dose of study treatment
    • In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by documented follow-up hormone level assessment

    1. Total abstinence if it is the preferred and constant lifestyle of the subject. Thus, periodic abstinence such as ovulation, symptothermal, postovulation, calendar methods, and withdrawal are not acceptable methods of contraception

    2. Male sterilization surgery: at least 6 months prior to Screening (with the appropriate postvasectomy documentation of the absence of sperm in the ejaculate). For female subjects, the vasectomized male should be the only partner.

    3. Placement of established intrauterine device (IUD): IUD copper or IUD with progesterone

    4. Barrier method (condom and intravaginal spermicide, cervical caps with spermicide, diaphragma with spermicide) in combination with the following: established oral, injected, or implanted hormone methods of contraception or contraceptive patch

    • Subjects with a known hypersensitivity to any component of the OKZ drug product, adalimumab, or placebo

    • Subjects with a known hypersensitivity or contraindication to any component of the rescue medication

    • History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies

    • Subject's unwillingness or inability to follow the procedures outlined in the protocol

    • Other medical or psychiatric conditions or laboratory abnormalities that may increase potential risk associated with study participation and administration of investigational products, or that may affect study results interpretation and, as per the Investigator's judgment, make the subject ineligible

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Arthritis & Rheumatology Associates, P.C. Mesa Arizona United States 85210
    2 Arizona Arthritis & Rheumatology Associates, P.C. Phoenix Arizona United States 85032
    3 Arizona Arthritis & Rheumatology Research, PLLC Sun City Arizona United States 85351
    4 Medvin Clinical Research Covina California United States 91722
    5 TriWest Research Associates El Cajon California United States 92020
    6 Rheumatology Center of San Diego Escondido California United States 92025
    7 MD Med Corp. Hemet California United States 92543
    8 Advanced Medical Research, LLC La Palma California United States 90623
    9 Valerius Medical Group Los Alamitos California United States 90720
    10 East Bay Rheumatology Medical Group, Inc. San Leandro California United States 94578
    11 Pacific Arthritis Center Medical Grpoup Santa Maria California United States 93454
    12 Stanford University School of Medicine Stanford California United States 94305
    13 Inland Rheumatology Clinical Trials Upland California United States 91786
    14 Nazanin Firooz, MD Inc. West Hills California United States 91607
    15 Medvin Clinical Research Whittier California United States 90602
    16 Denver Arthritis Clinic Denver Colorado United States 80230
    17 Arthritis & Osteoporosis Center PC Hamden Connecticut United States 06518
    18 New England Research Associates LLC Trumbull Connecticut United States 06606
    19 Delaware Arthritis Lewes Delaware United States 19958
    20 Javed Rheumatology Associates Newark Delaware United States 19713
    21 RASF - Clinical Research Center Boca Raton Florida United States 33486
    22 Reliable Clinical Research, LLC Hialeah Florida United States 33012
    23 Pharmax Research Clinic, Inc. Miami Florida United States 33126
    24 Florida Medical Center & Research Inc Miami Florida United States 33142
    25 Medical Research Center of Miami Miami Florida United States 33144
    26 Suncoast Clinical Research Inc. New Port Richey Florida United States 34652
    27 Omega Research Consultants Orlando Florida United States 32810
    28 Arthritis Research of Florida, Inc. Palm Harbor Florida United States 34684
    29 Family Clinical Trials, LLC. Pembroke Pines Florida United States 33026
    30 McIlwain Medical Group, PA Tampa Florida United States 33613
    31 AdventHealth Medical Group, PA Tampa Florida United States 33614
    32 Lovelace Scientific Resources, Inc. Venice Florida United States 34292
    33 Arthritis Center of North Georgia Gainesville Georgia United States 30501
    34 Marietta Rheumatology Associates, PC Marietta Georgia United States 30060
    35 Institute of Arthritis Research Idaho Falls Idaho United States 83404
    36 Advanced Clinical Research Meridian Idaho United States 83642
    37 Rush University Medical Center Chicago Illinois United States IL 60612
    38 Springfield Clinic, LLP Springfield Illinois United States 62703
    39 University of Kansas Medical Center Research Institute, Inc. Kansas City Kansas United States 66103
    40 Graves Gilbert Clinic Bowling Green Kentucky United States 42101
    41 The Arthritis & Diabetes Clinic, Inc. Monroe Louisiana United States 71203
    42 Klein and Associates, M.D., P.A. Hagerstown Maryland United States 21740
    43 The Center for Rheumatology and Bone Research Wheaton Maryland United States 20902
    44 AA MRC LLC Ahmed Arif Medical Research Center Grand Blanc Michigan United States 48439
    45 North MS Medical Clinics, Inc. Tupelo Mississippi United States 38801
    46 Glacier View Research Instutute-Rheumatology Kalispell Montana United States 59901
    47 Physician Resrch Collaboration Lincoln Nebraska United States 68516
    48 Westroads Clinical Research Omaha Nebraska United States 68114
    49 Allied Clinical Research Reno Nevada United States 89519
    50 Arthritis & Osteoporosis Associates, PA Freehold New Jersey United States 07728
    51 Lovelace Scientific Resources, Inc. Albuquerque New Mexico United States 87114
    52 NYU Langone ambulatory care Brooklyn New York United States 11201
    53 Medication Management, LLC Greensboro North Carolina United States 27408
    54 Cape Fear Arthritis Care Leland North Carolina United States 28451
    55 Trinity Medical Group Minot North Dakota United States 58701
    56 STAT Research, Inc. Dayton Ohio United States 45417
    57 Clinical Research Source, Inc. Toledo Ohio United States 43606
    58 Health Research of Oklahoma, PLLC Oklahoma City Oklahoma United States 73103
    59 Lynn Health Science Institute Oklahoma City Oklahoma United States 73112
    60 Altoona Center for Clinical Research, P.C. Duncansville Pennsylvania United States 16635
    61 Arthritis Group Philadelphia Pennsylvania United States 19152
    62 Low Country Rheumatology, PA North Charleston South Carolina United States 29406
    63 Amarillo Center for Clinical Research Amarillo Texas United States 79124
    64 Austin Regional Clinic, P.A. Austin Texas United States 78731
    65 Accurate Clinical Management LLC Baytown Texas United States 77521
    66 Pioneer Research Solutions, Inc. Beaumont Texas United States 77702
    67 Precision Comprehensive Clinical Research Solutions Grapevine Texas United States 76034
    68 Accurate Clinical Research, Inc. Houston Texas United States 77034
    69 Rheumatology Clinic of Houston, P.A. Houston Texas United States 77065
    70 Accurate Clinical Mgmt, LLC Houston Texas United States 77084
    71 Accurate Clinical Mangemnt LLC Houston Texas United States 77089
    72 Advanced Rheumatology of Houston Houston Texas United States 77382
    73 Pioneer Research Solutions, Inc. Houston Texas United States 77429
    74 Accurate Clinical Research, Inc. League City Texas United States 77573
    75 Endocrinology, Internal Medicine Lubbock Texas United States 79410
    76 Dr. Alex De Jesus Rheumatology, P.A. San Antonio Texas United States 78229
    77 DM Clinical Research Tomball Texas United States 77375
    78 Arthritis Northwest, PLLC Spokane Washington United States 99204
    79 Hospital Italiano Regional del Sur Bahia Blanca Buenos Aires Argentina B8001HXM
    80 Centro de Investigaciones Medicas Mar del Plata Mar del Plata Buenos Aires Argentina B7600FYK
    81 Instituto de Investigaciones Clinicas-Mar del Plata Mar del Plata Buenos Aires Argentina B7600FZ
    82 Instituto Medico CER Quilmes Buenos Aires Argentina B1878DVB
    83 Clinica de Higado y Aparato Digestivo Rosario Santa Fe Argentina S2000
    84 Sanatorio San Martin Venado Tuerto Santa Fe Argentina S2600KUE
    85 Centro Medico Privado de Reumatologia San Miguel de Tucuman Tucuman Argentina T4000AXL
    86 Centro de Investigaciones Reumatológicas San Miguel de Tucuman Tucuman Argentina T4000BRD
    87 Instituto de Asistencia Buenos Aires Argentina B1646DBM
    88 Institute Investigaciones Clinc Quilme Buenos Aires Argentina B1878GEG
    89 Organizacion Medica de Investigacion (OMI) Ciudad Autonoma Buenos Aires Argentina C1015ABO
    90 APRILLUS Ciudad Autonoma Buenos aires Argentina C1046AAQ
    91 Instituto Centenario Ciudad Autonoma Buenos Aires Argentina C1204AAD
    92 Atencion Integral en Reumatologia (AIR) Ciudad Autonoma Buenos Aires Argentina C1426AAL
    93 Instituto DAMIC Fundacion Rusculleda Cordoba Argentina X5003DCE
    94 Hospital Privado Centro Cordoba Argentina X5016KEH
    95 Centro Polivalente de Asistencia e Inv. Clinica CER San Juan Argentina J5402DIL
    96 HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará Fortaleza Ceará Brazil 60430-370
    97 CEDOES - Diagnóstico e Pesquisa Vitória Espírito Santo Brazil 29055-450
    98 CIP - Centro Internacional de Pesquisa Goiânia Goiás Brazil 74110-120
    99 CMiP - Centro Mineiro de Pesquisa Juiz de Fora Minas Gerais Brazil 36010-570
    100 CETI - Centro de Estudos em Terapias Inovadoras Ltda. Curitiba Paraná Brazil 80030-110
    101 Clinilive - Clínica do Idoso e Pesquisa Clínica Maringá Paraná Brazil 87015-180
    102 Hospital Bruno Born Lajeado Rio Grande Do Sul Brazil 95900-010
    103 Hospital Sao Vicente de Paulo Passo Fundo Rio Grande Do Sul Brazil 99010-080
    104 LMK Serviços Médicos S/S Ltda Porto Alegre Rio Grande Do Sul Brazil 90480-000
    105 Faculdade de Medicina do ABC Santo André Sao Paulo Brazil 09060-870
    106 Hospital Estadual Mário Covas Santo André Sao Paulo Brazil 9190510
    107 HUCFF-UFRJ - Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil 21941-913
    108 CCBR Brasil Centro de Pesquisas e Análises Clínicas Ltda. Rio de Janeiro Brazil 22271-100
    109 Clínica de Neoplasias Litoral Santa Catarina Brazil 88301-220
    110 CPCLIN - Centro de Pesquisas Clínicas Ltda. São Paulo Brazil 01228-200
    111 Hospital Abreu Sodré - AACD São Paulo Brazil 04023-000
    112 UMHAT Pulmed OOD Plovdiv Bulgaria 4000
    113 MHAT - Ruse, AD Ruse Bulgaria 7002
    114 Medizinski Zentar-1-Sevlievo EOOD Sevlievo Bulgaria 5400
    115 MHAT - Shumen, AD Shumen Bulgaria 9700
    116 Medical Center "Excelsior", OOD Sofia Bulgaria 1000
    117 NMTH "Tsar Boris III" Sofia Bulgaria 1233
    118 MHAT "Lyulin", EAD Sofia Bulgaria 1336
    119 UMHAT Sv. Ivan Rilski EAD Sofia Bulgaria 1431
    120 MC Synexus - Sofia EOOD Sofia Bulgaria 1784
    121 MDHAT 'Dr. Stefan Cherkezov', AD Veliko Tarnovo Bulgaria 5000
    122 Centro de Investigacion Medico Barranquilla Atlantico Colombia 080020
    123 Hospital Pablo Tobón Uribe Antioquia Colombia 050034
    124 Fundacion Instituto de Reumatologia Fernando Chalem Bogota Colombia 111211
    125 Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM Bogotá Colombia 110221
    126 Medicity S.A.S. Bucaramanga Colombia 680003
    127 Clinica de Artritis Temprana S.A. Cali Colombia 76001
    128 CCR Brno s.r.o Brno Czechia 602 00
    129 Revmatologie s.r.o. Brno Czechia 638 00
    130 Revmatologicka ambulance Jihlava Czechia 586 33
    131 Revmatologicka a interni ambulance Kladno Czechia 272 01
    132 CTCenter MaVe s.r.o. Olomouc Czechia 77900
    133 Artroscan s.r.o. Ostrava - Trebovice Czechia 722 00
    134 Vesalion s.r.o. Ostrava Czechia 70200
    135 ARTHROHELP s.r.o. Pardubice Czechia 530 02
    136 CCR Pardubice Pardubice Czechia 53002
    137 Clintrial, s.r.o. Praha 10 Czechia 120 00
    138 CCR Praha Praha 1 Czechia 101 00
    139 Revmatologicka ambulance Praha 4 Nusle Czechia 140 00
    140 Nuselska poliklinika Praha 4 Czechia 140 00
    141 Fakultni nemocnice v Motole Praha 5 Czechia 150 06
    142 Revmatologicky ustav Praha Czechia 128 52
    143 Affidea Praha, s.r.o. Praha Czechia 148 00
    144 MEDICAL PLUS s.r.o. Uherske Hradiste Czechia 686 01
    145 PV - Medical, s.r.o. Zlin Czechia 760 01
    146 East Tallinn Central Hospital Tallinn Estonia 11312
    147 Medita Kliinik OÜ Tartu Estonia 50406
    148 Kerckhoff-Klinik gGmbH Bad Nauheim Hessen Germany 61231
    149 CIRI - Centrum für Innovative Diagnostik und Therapie GmbH Frankfurt Hessen Germany 60590
    150 SMO.MD GmbH Magdeburg Sachsen Anhalt Germany 39120
    151 Rheumapraxis Dr. med. Reiner Kurthen Aachen Westfalen Germany D 52064
    152 Charité Universitätsmedizin Berlin Dpt. of Dermatology Venerology and Allergology Berlin Germany 10117
    153 Klinische Forschung Berlin-Mitte GmbH Berlin Germany 10117
    154 HRF Hamburger Rheuma Forschungszentrum Hamburg Germany 20095
    155 Studienambulanz Dr. Wassenberg Northeim Germany 40878
    156 Principal SMO Kft. Baja Hungary H-6500
    157 DRC Gyogyszervizsgalo Kozpont Kft. Balatonfured Hungary 8230
    158 Clinexpert Egeszsegugyi Szolg. es Ker. Kft. Budapest Hungary 1033
    159 Obudai Egeszsegugyi Centrum Budapest Hungary 1036
    160 Debreceni Egyetem Klinikai Kozpont Debrecen Hungary 4032
    161 Kiskunhalasi Semmelweis Korhaz Kiskunhalas Hungary 6400
    162 DRC Szekesfehervar Szekesfehervar Hungary 8000
    163 MAV Korhaz és Rendelointezet Szolnok Hungary 5000
    164 Vital Medical Center Veszprem Hungary 8200
    165 Hanyang University Seoul Hosp Seoul Seongdong-gu Korea, Republic of 04763
    166 Chonbuk National University Hospital Chungbuk Korea, Republic of 54907
    167 Eulji University Hospital Daejeon Korea, Republic of 35233
    168 Chonnam National University Hospital Gwangju Korea, Republic of 61469
    169 CHA Bundang Medical Center Gyeonggi-do Korea, Republic of 13496
    170 Jeju National University Hospital Jeju Korea, Republic of 63241
    171 Severance Hospital, Yonsei University Seoul Korea, Republic of 03722
    172 The Catholic University of Korea, Seoul St. Mary's Hospital Seoul Korea, Republic of 06591
    173 Dr.Saulite-Kandevica Private Practice Liepaja Latvia LV-3401
    174 GK Neuroklinika Riga Latvia LV1024
    175 Alytаus Regional S. Kudirkos Hospital, Public Institution Alytus Lithuania 62114
    176 Republican Kaunas Hospital, Public Institution Kaunas Lithuania 45130
    177 Klaipeda University Hospital, Public Institution Klaipeda Lithuania 92288
    178 Siauliai Republican Hospital, Public Institution Siauliai Lithuania 76231
    179 Vilnius University Hospital Santariskiu Clinic, Public Institution Vilnius Lithuania LT-08661
    180 Center Outpatient Clinic, Public Institution Vilnius Lithuania LT01117
    181 Centro de Investigacion Clínica GRAMEL S.C Mexico DisMexicotrito Federal Mexico 03720
    182 Clinstile, S.A. de C.V. Mexico Distrito Federal Mexico 06700
    183 Comite Mexicano Para la Prevencion de Osteoporosis AC Mexico Distrito Federal Mexico 16100
    184 Clinicos Asociados BOCM S.C. Mexico Distrito Federal Mexico 3300
    185 Clinical Research Institute S.C. Tlalnepantla Estado De Mexico Mexico 54055
    186 Clinica de Investigacion en Reumatologia y Obesidad S.C. Guadalajara Jalisco Mexico 44650
    187 Centro de Estudios de Investigacion Basica y Clinica SC Guadalajara Jalisco Mexico 44690
    188 Accelerium S. de R.L. de C.V. Monterrey Nuevo León Mexico 64000
    189 Hospital Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez Monterrey Nuevo León Mexico 64460
    190 Investigacion y Biomedicina de Chihuahua, S.C. Chihuahua Mexico 31000
    191 Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C. San Luis Potosi Mexico 78213
    192 CERMED Bialystok Poland 15-270
    193 NZOZ ZDROWIE Osteo-Medic Bialystok Poland 15-351
    194 Szpital Uniwersytecki nr 2 im.dr J. Biziela Bydgoszcz Poland 85-168
    195 Szpital Specjalistyczny nr 1 w Bytomiu Bytom Poland 41902
    196 McBk S.C. Grodzisk Mazowiecki Poland 05-825
    197 Polimedica Centrum Badań, Profilaktyki I Leczenia Kielce Poland 25-355
    198 Centrum Medyczne AMED Lodz Poland 91-363
    199 ETYKA Osrodek Badan Klinicznych Olsztyn Poland 10-117
    200 Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego Sieradz Poland 98-200
    201 CCBR - Lodz - PL Skierniewice Poland 90 368
    202 Centrum Medyczne Ogrodowa Skierniewice Poland 96-100
    203 RCMed Sochaczew Poland 96-500
    204 KO-MED Centra Kliniczne Staszow Staszow Poland 28-200
    205 SPZOZ Tomaszow Lubelski Tomaszow Lubelski Poland 22-600
    206 Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z Torun Poland 87-100
    207 Medycyna Kliniczna Warszawa Poland 00-874
    208 Rheuma Medicus Zaklad Opieki Zdrowotnej Warszawa Poland 02-118
    209 McM Polimedica Wysokie Mazowieckie Poland 02777
    210 KO-MED Centra Kliniczne Zamosc Zamosc Poland 22-400
    211 "POLIMEDICA Centrum Badan Zgierz Poland 95-100
    212 Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta Constanta Romania 900591
    213 Mediab SRL Targu Mures Romania 540142
    214 City Hospital 4 Barnaul Altai Region Russian Federation 656055
    215 Hospital for War Veterans Kemerovo Kemerowo Oblast Russian Federation 650000
    216 Kursk Clinical Hospital Kursk Kursk Oblast Russian Federation 305507
    217 Medical Center n a Almazov Saint-Petersburg Leningrad Oblast Russian Federation 197341
    218 SPb SBHI "Clinical Rheumatological Hospital #25", Fourth Rheumatology Unit Saint Petersburg Leningradskaya Oblast Russian Federation 190068
    219 FSBEI HE "FMSMU n.a. I.M. Sechenov of MoH of RF", University Hospital #2, Departament of New Drugs Introduction Moscow Moscovskaya Oblast Russian Federation 119991
    220 University hospital 3 Moscow Moscow Oblast Russian Federation 119991
    221 Clinical Hospital 1 Moscow Moscow Oblast Russian Federation 119992
    222 State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department Moscow Moscow Region Russian Federation 111539
    223 SBHI of Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital n.a.Semashko" Nizhniy Novgorod Nizhegorodskaya Oblast Russian Federation 603126
    224 Institute of Therapy Novosibirsk Novosibirsk Oblast Russian Federation 630089
    225 City Clinical Hospital 1 Novosibirsk Novosibirsk Oblast Russian Federation 630099
    226 Hospital n a Kuvatov Ufa Republic Of Bashkortostan Russian Federation 450005
    227 SBHI of Republic of Karelia "Republican Hospital named after V.A.Baranov" Petrozavodsk Republic Of Karelia Russian Federation 185019
    228 Non-govarnmental Healtheare Institution "Regional Clinical Hospital at Smolensk station of OJSC "Russian Railways" Smolensk Smolenskaya Oblast Russian Federation 214025
    229 Stavropol Clinical Hospital Stavropol Stavropol Krai Russian Federation 355000
    230 State Budgetary Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital #1" Ekaterinburg Sverdlovskaya Oblast Russian Federation 620102
    231 SBEI HPE "Ural State Medical University" of MoH of RF based MBI "Central City Clinical Hospital #6" Ekaterinburg Sverdlovskaya Oblast Russian Federation 620149
    232 State Autonomous Healthcare Institution "Republican Clinical Hospital of Ministry of Health of Tatarstan Republic Kazan' The Republic Of Tatarstan Russian Federation 420064
    233 Regional Clinical Hospital Vladimir Vladimir Oblast Russian Federation 600023
    234 "University n a Burdenko Voronezh Voronezh Oblast Russian Federation 394066
    235 Yaroslavl Clinical Hospital Yaroslavl Yaroslavl Oblast Russian Federation 150062
    236 Institute n a Nasonova Moscow Russian Federation 115478
    237 Chi Mei Medical Center Tainan Taiwan 710
    238 Chang Gung Memorial Hospital, Linkou Taoyuan Taiwan 333
    239 Torbay Hospital Torquay Devon United Kingdom TQ2 7AA
    240 Whipps Cross University Hospital London Greater London United Kingdom E11 1NR
    241 Royal Free Hospital London Greater London United Kingdom NW3 2QG
    242 Basingstoke and North Hampshire Hospital Basingstoke Hampshire United Kingdom RG24 9NA
    243 Maidstone Hospital Maidstone Kent United Kingdom ME16 9QQ
    244 Arrowe Park Hospital Wirral Merseyside United Kingdom CH49 5PE
    245 Glasgow Royal Infirmary Glasgow Strathclyde United Kingdom G4 0SF

    Sponsors and Collaborators

    • R-Pharm International, LLC
    • Quintiles, Inc.
    • OCT Clinical Trials

    Investigators

    • Study Director: Mikhail Samsonov, R-Pharm

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    R-Pharm International, LLC
    ClinicalTrials.gov Identifier:
    NCT02760407
    Other Study ID Numbers:
    • CL04041023
    First Posted:
    May 3, 2016
    Last Update Posted:
    Apr 30, 2021
    Last Verified:
    Apr 1, 2021
    Keywords provided by R-Pharm International, LLC
    moderate Rheumatoid Arthritis
    severe Rheumatoid Arthritis
    subcutaneous
    Olokizumab
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid
    Adalimumab

    Study Results

    Participant Flow

    Recruitment Details Enrollment was conducted at 209 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.
    Pre-assignment Detail
    Arm/Group Title Arm 1: Olokizumab q4w Arm 2: Olokizumab q2w Arm 3: Adalimumab q2w Arm 4: Placebo q2w
    Arm/Group Description 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) 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) 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) 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)
    Period Title: Overall Study
    STARTED 479 464 462 243
    COMPLETED 443 421 412 207
    NOT COMPLETED 36 43 50 36

    Baseline Characteristics

    Arm/Group Title Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate Total
    Arm/Group Description 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) 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) 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) 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 of all reporting groups
    Overall Participants 479 464 462 243 1648
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    389
    81.2%
    379
    81.7%
    367
    79.4%
    192
    79%
    1327
    80.5%
    >=65 years
    90
    18.8%
    85
    18.3%
    95
    20.6%
    51
    21%
    321
    19.5%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    53.7
    (12.09)
    53.3
    (11.92)
    54.3
    (12.32)
    54.7
    (11.85)
    53.9
    (12.07)
    Sex: Female, Male (Count of Participants)
    Female
    378
    78.9%
    352
    75.9%
    363
    78.6%
    190
    78.2%
    1283
    77.9%
    Male
    101
    21.1%
    112
    24.1%
    99
    21.4%
    53
    21.8%
    365
    22.1%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    6
    1.3%
    10
    2.2%
    4
    0.9%
    5
    2.1%
    25
    1.5%
    Black or African American
    15
    3.1%
    20
    4.3%
    23
    5%
    11
    4.5%
    69
    4.2%
    White
    406
    84.8%
    382
    82.3%
    385
    83.3%
    203
    83.5%
    1376
    83.5%
    Other/Mixed
    52
    10.9%
    52
    11.2%
    50
    10.8%
    24
    9.9%
    178
    10.8%
    Region of Enrollment (participants) [Number]
    Colombia
    18
    3.8%
    17
    3.7%
    16
    3.5%
    8
    3.3%
    59
    3.6%
    Argentina
    44
    9.2%
    42
    9.1%
    43
    9.3%
    24
    9.9%
    153
    9.3%
    Romania
    0
    0%
    0
    0%
    1
    0.2%
    0
    0%
    1
    0.1%
    Hungary
    15
    3.1%
    13
    2.8%
    13
    2.8%
    10
    4.1%
    51
    3.1%
    United States
    75
    15.7%
    71
    15.3%
    72
    15.6%
    39
    16%
    257
    15.6%
    Czechia
    58
    12.1%
    50
    10.8%
    51
    11%
    30
    12.3%
    189
    11.5%
    United Kingdom
    3
    0.6%
    1
    0.2%
    6
    1.3%
    1
    0.4%
    11
    0.7%
    Russia
    20
    4.2%
    21
    4.5%
    25
    5.4%
    11
    4.5%
    77
    4.7%
    Latvia
    1
    0.2%
    3
    0.6%
    0
    0%
    0
    0%
    4
    0.2%
    South Korea
    2
    0.4%
    4
    0.9%
    1
    0.2%
    4
    1.6%
    11
    0.7%
    Taiwan
    2
    0.4%
    3
    0.6%
    2
    0.4%
    1
    0.4%
    8
    0.5%
    Brazil
    33
    6.9%
    33
    7.1%
    30
    6.5%
    16
    6.6%
    112
    6.8%
    Poland
    90
    18.8%
    85
    18.3%
    87
    18.8%
    46
    18.9%
    308
    18.7%
    Mexico
    63
    13.2%
    63
    13.6%
    59
    12.8%
    30
    12.3%
    215
    13%
    Bulgaria
    18
    3.8%
    20
    4.3%
    19
    4.1%
    8
    3.3%
    65
    3.9%
    Lithuania
    22
    4.6%
    22
    4.7%
    22
    4.8%
    8
    3.3%
    74
    4.5%
    Germany
    11
    2.3%
    13
    2.8%
    10
    2.2%
    6
    2.5%
    40
    2.4%
    Estonia
    4
    0.8%
    3
    0.6%
    5
    1.1%
    1
    0.4%
    13
    0.8%
    Body Mass Index (BMI) (kg/m^2) [Mean (Full Range) ]
    Mean (Full Range) [kg/m^2]
    28.654
    28.656
    28.532
    28.573
    28.609

    Outcome Measures

    1. Primary Outcome
    Title ACR20 Response
    Description 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 is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12) This endpoint will serve to demonstrate that the efficacy of OKZ is 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)
    Time Frame at Week 12

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Arm/Group Description 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) 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) 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) 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)
    Measure Participants 479 464 462 243
    Count of Participants [Participants]
    342
    71.4%
    326
    70.3%
    309
    66.9%
    108
    44.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 1: Olokizumab q4w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments The OKZ ACR20 response rate for the 64 mg q4w treatment group at Week 12 was expected to be at least 50% resulting in an expected difference in ACR20 response rates of 25 percentage points between the respective OKZ treatment group and placebo. Sample size yield 100% disjunctive power for testing the primary hypothesis
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.270
    Confidence Interval (2-Sided) 97.5%
    0.183 to 0.352
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm 2: Olokizumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments The OKZ ACR20 response rate for the 64 mg q2w treatment group at Week 12 was expected to be at least 55%, resulting in an expected difference in ACR20 response rate of 30 percentage points between the respective OKZ treatment group and placebo. Sample size yield 100% disjunctive power for testing the primary hypothesis
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.258
    Confidence Interval (2-Sided) 97.5%
    0.171 to 0.341
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title ACR20 Response and to Demonstrate That the Efficacy of OKZ is Non-inferior to Adalimumab
    Description Where a responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. This endpoint will serve to demonstrate that the efficacy of OKZ is non-inferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) is 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)
    Time Frame at Week 12

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Arm/Group Description 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) 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) 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) 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)
    Measure Participants 479 464 462 243
    Count of Participants [Participants]
    342
    71.4%
    326
    70.3%
    309
    66.9%
    108
    44.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 3: Adalimumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments The ACR20 response rate for adalimumab was expected to be at least 52.5% at Week 12.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.224
    Confidence Interval (2-Sided) 95%
    0.148 to 0.298
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm 1: Olokizumab q4w + Methotrexate, Arm 3: Adalimumab q2w + Methotrexate
    Comments A noninferiority margin of 12% was used for the comparison between OKZ and adalimumab with respect to this endpoint.
    Type of Statistical Test Non-Inferiority
    Comments Non-Inferiority for each OKZ dosing regimen versus Adalimumab is achieved if the lower limit of the 97.5% confidence interval is greater than the protocol defined non-inferiority margin of -12%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.045
    Confidence Interval (2-Sided) 97.5%
    -0.022 to 0.112
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm 2: Olokizumab q2w + Methotrexate, Arm 3: Adalimumab q2w + Methotrexate
    Comments A noninferiority margin of 12% was used for the comparison between OKZ and adalimumab with respect to this endpoint.
    Type of Statistical Test Non-Inferiority
    Comments Non-Inferiority for each OKZ dosing regimen versus Adalimumab is achieved if the lower limit of the 97.5% confidence interval is greater than the protocol defined non-inferiority margin of -12%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.034
    Confidence Interval (2-Sided) 97.5%
    -0.035 to 0.102
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Difference Between OKZ and Placebo in the Percentage of Subjects Achieving Low Disease Activity
    Description 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
    Time Frame at Week 12

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Arm/Group Description 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) 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) 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) 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)
    Measure Participants 479 464 462 243
    Count of Participants [Participants]
    219
    45.7%
    210
    45.3%
    177
    38.3%
    31
    12.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 1: Olokizumab q4w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments The DAS28 low disease activity (based on DAS28 [CRP] <3.2) response rate at Week 12 is estimated to be 10% in the placebo group and 22% in the 64 mg q4w OKZ group, resulting in an expected difference of 12 percentage points between respective OKZ group and placebo.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.330
    Confidence Interval (2-Sided) 97.5%
    0.255 to 0.395
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm 2: Olokizumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments The DAS28 low disease activity (based on DAS28 [CRP] <3.2) response rate at Week 12 is estimated to be 10% in the placebo group and 30% in the 64 mg q2w OKZ group, resulting in an expected difference of 20 percentage points between respective OKZ group and placebo.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.325
    Confidence Interval (2-Sided) 97.5%
    0.250 to 0.391
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Difference Between Adalimumab and OKZ in Percentage of Subjects Achieving Low Disease Activity, Defined as DAS28 (CRP) <3.2
    Description 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
    Time Frame at Week 12

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Arm/Group Description 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) 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) 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) 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)
    Measure Participants 479 464 462 243
    Count of Participants [Participants]
    219
    45.7%
    210
    45.3%
    177
    38.3%
    31
    12.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 3: Adalimumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments The DAS28 low disease activity response rate for adalimumab was expected to be at least 27% at Week 12.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.256
    Confidence Interval (2-Sided) 95%
    0.191 to 0.313
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm 1: Olokizumab q4w + Methotrexate, Arm 3: Adalimumab q2w + Methotrexate
    Comments A noninferiority margin of 7.5% was used for the comparison between OKZ and adalimumab with respect to this endpoint.
    Type of Statistical Test Non-Inferiority
    Comments Non-Inferiority for each OKZ dosing regimen versus Adalimumab is achieved if the lower limit of the 97.5% confidence interval is greater than the protocol defined noninferiority margin of -7.5%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.074
    Confidence Interval (2-Sided) 97.5%
    0.002 to 0.145
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm 2: Olokizumab q2w + Methotrexate, Arm 3: Adalimumab q2w + Methotrexate
    Comments A noninferiority margin of 7.5% was used for the comparison between OKZ and adalimumab with respect to this endpoint.
    Type of Statistical Test Non-Inferiority
    Comments Non-Inferiority for each OKZ dosing regimen versus Adalimumab is achieved if the lower limit of the 97.5% confidence interval is greater than the protocol defined noninferiority margin of -7.5%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.069
    Confidence Interval (2-Sided) 97.5%
    -0.003 to 0.141
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Improvement of Physical Ability From Baseline to Week 12, as Measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI)
    Description Difference between OKZ and placebo in the improvement of physical ability. Improvement of physical ability from baseline 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 to 3, with higher scores indicating greater disability.
    Time Frame Baseline to Week 12

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Arm/Group Description 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) 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) 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) 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)
    Measure Participants 479 464 462 243
    Baseline
    1.69
    (0.602)
    1.73
    (0.580)
    1.72
    (0.571)
    1.71
    (0.616)
    Week 12 (Visit 9)
    1.09
    (0.637)
    1.07
    (0.654)
    1.10
    (0.667)
    1.26
    (0.659)
    Change from baseline (observed)
    -0.60
    (0.592)
    -0.66
    (0.617)
    -0.63
    (0.594)
    -0.44
    (0.557)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 1: Olokizumab q4w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.19
    Confidence Interval (2-Sided) 97.5%
    -0.29 to -0.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.046
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm 2: Olokizumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.22
    Confidence Interval (2-Sided) 97.5%
    -0.33 to -0.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.046
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm 3: Adalimumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Least Squares Mean Difference
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -0.28 to -0.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.046
    Estimation Comments
    6. Secondary Outcome
    Title ACR50 Response
    Description 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)
    Time Frame at Week 24

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Arm/Group Description 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) 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) 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) 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)
    Measure Participants 479 464 462 243
    Count of Participants [Participants]
    240
    50.1%
    234
    50.4%
    214
    46.3%
    55
    22.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 1: Olokizumab q4w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.275
    Confidence Interval (2-Sided) 97.5%
    0.192 to 0.349
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm 2: Olokizumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.278
    Confidence Interval (2-Sided) 97.5%
    0.195 to 0.353
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm 3: Adalimumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.237
    Confidence Interval (2-Sided) 95%
    0.165 to 0.303
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Clinical Disease Activity Index (CDAI) ≤2.8 (Remission)
    Description 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
    Time Frame at Week 24

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Arm/Group Description 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) 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) 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) 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)
    Measure Participants 479 464 462 243
    Count of Participants [Participants]
    58
    12.1%
    52
    11.2%
    60
    13%
    10
    4.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 1: Olokizumab q4w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.080
    Confidence Interval (2-Sided) 97.5%
    0.031 to 0.123
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Arm 2: Olokizumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Chi-squared
    Comments 2x2 chi-square test
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.071
    Confidence Interval (2-Sided) 97.5%
    0.022 to 0.113
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Arm 3: Adalimumab q2w + Methotrexate, Arm 4: Placebo q2w + Methotrexate
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.089
    Confidence Interval (2-Sided) 95%
    0.046 to 0.127
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame 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
    Adverse Event Reporting Description 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
    Arm/Group Title Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Arm/Group Description 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) 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) 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) 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)
    All Cause Mortality
    Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/477 (0.4%) 3/463 (0.6%) 1/462 (0.2%) 1/243 (0.4%)
    Serious Adverse Events
    Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 22/477 (4.6%) 27/463 (5.8%) 44/462 (9.5%) 13/243 (5.3%)
    Blood and lymphatic system disorders
    Anaemia 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Microcytic anaemia 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Pancytopenia 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Cardiac disorders
    Pericarditis 0/477 (0%) 0 0/463 (0%) 0 2/462 (0.4%) 2 0/243 (0%) 0
    Atrial fibrillation 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Myocardial infarction 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Myocardial ischaemia 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Eye disorders
    Cataract 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Gastrointestinal disorders
    Colitis 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Diverticulum intestinal 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Food poisoning 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Gastrointestinal inflammation 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Pneumoperitoneum 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    General disorders
    Injection site inflammation 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Non-cardiac chest pain 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Polyp 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Pyrexia 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Sudden death 0/477 (0%) 0 0/463 (0%) 0 0/462 (0%) 0 1/243 (0.4%) 1
    Hepatobiliary disorders
    Hepatotoxicity 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 2/243 (0.8%) 2
    Cholecystitis 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Cholelithiasis 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Hepatic steatosis 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Infections and infestations
    Pneumonia 1/477 (0.2%) 1 1/463 (0.2%) 1 6/462 (1.3%) 6 0/243 (0%) 0
    Sepsis 1/477 (0.2%) 1 1/463 (0.2%) 1 2/462 (0.4%) 2 0/243 (0%) 0
    Urosepsis 0/477 (0%) 0 0/463 (0%) 0 2/462 (0.4%) 2 2/243 (0.8%) 2
    Cellulitis 2/477 (0.4%) 2 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Urinary tract infection 0/477 (0%) 0 0/463 (0%) 0 2/462 (0.4%) 2 0/243 (0%) 0
    Intervertebral discitis 0/477 (0%) 0 1/463 (0.2%) 1 1/462 (0.2%) 1 0/243 (0%) 0
    Abdominal abscess 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Abscess limb 0/477 (0%) 0 0/463 (0%) 0 0/462 (0%) 0 1/243 (0.4%) 1
    Appendicitis 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Bronchitis 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Gastroenteritis 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Herpes zoster 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Keratouveitis 0/477 (0%) 0 0/463 (0%) 0 0/462 (0%) 0 1/243 (0.4%) 1
    Latent tuberculosis 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Lyme disease 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Pharyngitis streptococcal 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Postoperative wound infection 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Pulmonary tuberculosis 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Respiratory tract infection 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Septic shock 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Erysipelas 1/477 (0.2%) 1 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Injury, poisoning and procedural complications
    Femur fracture 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Tibia fracture 0/477 (0%) 0 0/463 (0%) 0 0/462 (0%) 0 1/243 (0.4%) 1
    Investigations
    Alanine aminotransferase increased 2/477 (0.4%) 2 2/463 (0.4%) 2 2/462 (0.4%) 2 0/243 (0%) 0
    Transaminases increased 0/477 (0%) 0 2/463 (0.4%) 2 0/462 (0%) 0 1/243 (0.4%) 1
    Hepatic enzyme increased 0/477 (0%) 0 0/463 (0%) 0 0/462 (0%) 0 1/243 (0.4%) 1
    Metabolism and nutrition disorders
    Hypoglycaemia 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc disorder 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Joint effusion 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Osteoarthritis 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Papillary thyroid cancer 1/477 (0.2%) 1 1/463 (0.2%) 1 0/462 (0%) 0 1/243 (0.4%) 1
    Prostate cancer 1/477 (0.2%) 1 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Adenocarcinoma of colon 0/477 (0%) 0 0/463 (0%) 0 0/462 (0%) 0 1/243 (0.4%) 1
    Bladder transitional cell carcinoma stage IV 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Bronchial carcinoma 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Leiomyoma 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Lung adenocarcinoma stage III 0/477 (0%) 0 0/463 (0%) 0 0/462 (0%) 0 1/243 (0.4%) 1
    Nervous system disorders
    Cerebral haemorrhage 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Cerebral infarction 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Cerebrovascular accident 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Ischaemic stroke 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Sciatica 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Psychiatric disorders
    Confusional state 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Reproductive system and breast disorders
    Uterine prolapse 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease 0/477 (0%) 0 0/463 (0%) 0 2/462 (0.4%) 2 0/243 (0%) 0
    Pulmonary embolism 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Rheumatoid lung 0/477 (0%) 0 0/463 (0%) 0 1/462 (0.2%) 1 0/243 (0%) 0
    Surgical and medical procedures
    Surgery 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Vascular disorders
    Deep vein thrombosis 1/477 (0.2%) 1 1/463 (0.2%) 1 1/462 (0.2%) 1 0/243 (0%) 0
    Hypertension 1/477 (0.2%) 1 0/463 (0%) 0 0/462 (0%) 0 0/243 (0%) 0
    Thrombophlebitis 0/477 (0%) 0 1/463 (0.2%) 1 0/462 (0%) 0 0/243 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm 1: Olokizumab q4w + Methotrexate Arm 2: Olokizumab q2w + Methotrexate Arm 3: Adalimumab q2w + Methotrexate Arm 4: Placebo q2w + Methotrexate
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 177/477 (37.1%) 183/463 (39.5%) 129/462 (27.9%) 71/243 (29.2%)
    General disorders
    Injection site erythema 8/477 (1.7%) 8 8/463 (1.7%) 8 20/462 (4.3%) 20 2/243 (0.8%) 2
    Infections and infestations
    Nasopharyngitis 26/477 (5.5%) 26 29/463 (6.3%) 29 29/462 (6.3%) 29 18/243 (7.4%) 18
    Upper respiratory tract infection 29/477 (6.1%) 29 28/463 (6%) 28 26/462 (5.6%) 26 16/243 (6.6%) 16
    Urinary tract infection 14/477 (2.9%) 14 7/463 (1.5%) 7 19/462 (4.1%) 19 9/243 (3.7%) 9
    Bronchitis 10/477 (2.1%) 10 12/463 (2.6%) 12 11/462 (2.4%) 11 11/243 (4.5%) 11
    Investigations
    Alanine aminotransferase increased 53/477 (11.1%) 53 41/463 (8.9%) 41 9/462 (1.9%) 9 4/243 (1.6%) 4
    Aspartate aminotransferase increased 24/477 (5%) 24 23/463 (5%) 23 8/462 (1.7%) 8 2/243 (0.8%) 2
    Metabolism and nutrition disorders
    Hypercholesterolaemia 20/477 (4.2%) 20 29/463 (6.3%) 29 6/462 (1.3%) 6 3/243 (1.2%) 3
    Dyslipidaemia 15/477 (3.1%) 15 25/463 (5.4%) 25 4/462 (0.9%) 4 4/243 (1.6%) 4
    Hyperlipidaemia 10/477 (2.1%) 10 22/463 (4.8%) 22 5/462 (1.1%) 5 2/243 (0.8%) 2
    Nervous system disorders
    Headache 11/477 (2.3%) 11 10/463 (2.2%) 10 14/462 (3%) 14 12/243 (4.9%) 12
    Vascular disorders
    Hypertension 27/477 (5.7%) 27 25/463 (5.4%) 25 13/462 (2.8%) 13 8/243 (3.3%) 8

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Any study related information could be made public available only after Sponsors written permission.

    Results Point of Contact

    Name/Title Elena Korneva, Senior Scientific Advisor
    Organization R-Pharm
    Phone 0074959567937 ext 3819
    Email korneva@rpharm.ru
    Responsible Party:
    R-Pharm International, LLC
    ClinicalTrials.gov Identifier:
    NCT02760407
    Other Study ID Numbers:
    • CL04041023
    First Posted:
    May 3, 2016
    Last Update Posted:
    Apr 30, 2021
    Last Verified:
    Apr 1, 2021