BI 695501 Compared to Adalimumab in Patients With Active Rheumatoid Arthritis

Efficacy, Safety and Immunogenicity of BI 695501 Versus Adalimumab in Patients With Active Rheumatoid Arthritis: a Randomized, Double-blind,Parallel Arm, Multiple Dose, Active Comparator Trial

Primary Objective:

The primary objective of this trial is to establish an equivalence in efficacy between BI 695501 and US-licensed Humira® in patients with active Rheumatoid arthritis based on a statistical comparison of the proportion of patients meeting American College of Rheumatology 20% (ACR20) response rate at Week 12 and ACR20 response rate at Week 24 between BI 695501 and US-licensed Humira®.

Secondary Objectives:

The secondary objectives of this trial are to compare the efficacy, safety and immunogenicity of BI 695501 and US-licensed Humira® in patients with active RA including those undergoing the transition from US-licensed Humira® to BI 695501 after 24 weeks.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Drug: BI 695501; Drug: US-licensed Humira®

• Study Type: Interventional
• Enrollment (Actual): 645
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • MHAT "Trimontium", OOD, Plovdiv
  • Plovdiv, Bulgaria, 4002
    • MHAT "Eurohospital" - Plovdiv, OOD
  • Plovdiv, Bulgaria, 4002
    • MHAT - Kaspela, EOOD
  • Ruse, Bulgaria, 7000
    • Medical Center "Teodora", EOOD, Ruse
  • Ruse, Bulgaria, 7002
    • MHAT,Fourth Dept. of Therapeutics & Cardiology, Ruse
  • Shumen, Bulgaria, 9700
    • MHAT Shumen AD, Shumen
  • Sofia, Bulgaria, 1336
    • MHAT Lyulin
  • Sofia, Bulgaria, 1504
    • DCC 17 - Sofia EOOD
  • Sofia, Bulgaria, 1606
    • MMA HAT Sofia, Bulgaria
  • Sofia, Bulgaria, 1612
    • Umhat Sv. Ivan Rilski Ead
  • Varna, Bulgaria, 9000
    • DCC 'Chaika', EOOD, Varna
  • Veliko Tarnovo, Bulgaria, 5000
    • MDHAT 'Dr. Stefan Cherkezov', AD
• Chile
  • Osorno, Chile, 5290000
    • Corporacion de Beneficencia Osorno
  • Puerto Varas, Chile, 5550170
    • Quantum Research Santiago, Puerto Varas
  • Santiago, Chile, 7500710
    • BIOMEDICA, Santiago
  • Santiago, Chile, 7501126
    • Centro de Estudios Reumatologicos
  • Santiago, Chile, 7510047
    • Centro Medico Prosalud
  • Viña del Mar, Chile, 2570017
    • CINVEC - Centro de Investigacion Clinica V Reg.,Vina del Mar
• Estonia
  • Pärnu, Estonia, 80010
    • Pärnu Hospital, Pärnu
  • Tartu, Estonia, 50107
    • Medita Kliinik OÜ, Tartu
• Germany
  • Bad Doberan, Germany, 18209
    • Rheumazentrum Prof. Dr. G. Neeck, Bad Doberan
  • Bad Kreuznach, Germany, 55543
    • ACURA Kliniken Rheinland-Pfalz AG, Bad Kreuznach
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik, Bad Nauheim
  • Magdeburg, Germany, 39112
    • SMO.MD GmbH, Magdeburg
• Hungary
  • Szeged, Hungary, 6725
    • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klin. Kozpont
  • Veszprem, Hungary, 8200
    • Csolnoky Ferenc Korhaz, Veszprem
• Korea, Republic of
  • Daegu, Korea, Republic of, 705-718
    • Daegu Catholic University Medical Center
  • Daejeon, Korea, Republic of, 301-721
    • Chungnam National University Hospital
  • Seoul, Korea, Republic of, 143-729
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 110744
    • Seoul National University Hospital
• Malaysia
  • Kuantan, Malaysia, 25100
    • Hospital Tengku Ampuan Afzan
  • Pulau Pinang, Malaysia, 10990
    • Hospital Pulau Pinang
• New Zealand
  • Cantebury, New Zealand, 8022
    • CGM Research Trust, The Princess Margaret Hospital Cantebury
• Poland
  • Bialystok, Poland, 15-099
    • Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im.dr J. Biziela
  • Elblag, Poland, 82-300
    • Wojewodzki Szpital Zespolony w Elblagu
  • Gdynia, Poland, 81-338
    • Medica Pro Familia Spolka Akcyjna, Oddzial w Gdyni
  • Grodzisk Mazowiecki, Poland, 05-825
    • MCBK Iwona Czajkowska Anna Podrażka- Szczepaniak S.C.
  • Katowice, Poland, 40-954
    • Medical Centre Pratia Katowice I
  • Krakow, Poland, 30-002
    • Medical Centre Pratia Krakow
  • Krakow, Poland, 31-023
    • Specialist Center ALL-MED, Krakow
  • Torun, Poland, 87-100
    • Niepubliczny ZOZ, "Nasz Lekarz", Lekarzy Rodzinnych z
  • Warszawa, Poland, 01-868
    • Medical Centre Pratia Warszawa
  • Warszawa, Poland, 02-653
    • Reumatika, Rheumatology Center, non-public outpatient clinic
  • Wroclaw, Poland, 52-224
    • Wojewodzki Szpital Specjalistyczny we Wroclawiu
• Russian Federation
  • Kemerovo, Russian Federation, 650000
    • Kemerovo SMA b/o War Veterans Regional Clinical Hospital
  • Moscow, Russian Federation, 115404
    • Practicheskaya Meditsina Ltd
  • Petrozavodsk, Russian Federation, 185019
    • Republic Kareliya Republican Hosp. named after V.A. Baranov
  • Samara, Russian Federation, 443095
    • Samara Regional Clinical Hospital n.a MI Kalinin, Samara
  • Saratov, Russian Federation, 410002
    • Reg. Hospital for war veterans
  • Stavropol, Russian Federation, 355017
    • Stavropol State Medical Academy
  • Yaroslavl, Russian Federation, 150003
    • Emergency Clinical Hospital n. a. N. V. Soloviev, Yaroslavl
  • Yaroslavl, Russian Federation, 150051
    • SBHI of Yaroslavl Area "Clinical Hospital #3"
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology, Belgrade
  • Niska Banja, Serbia, 18205
    • Institute for Treatment and Rehabilitation, Niska Banja
  • Novi Sad, Serbia, 21 000
    • Clinical Center of Vojvodina
  • Sabac, Serbia, 15000
    • General Hospital "Dr Laza K. Lazarevic" Sabac, Sabac
• Spain
  • Barakaldo, Spain, 48903
    • Hospital Universitario de Cruces
  • La Coruña, Spain, 15006
    • Hospital A Coruña
  • Madrid, Spain, 28040
    • Fundación Jiménez Díaz
  • Santiago de Compostela, Spain, 15705
    • Hosp. Nuestra Señora de la Esperanza, Santiago de Compostela
  • Santiago de Compostela, Spain, 15706
    • Hospital Clínico de Santiago
• Thailand
  • Bangkoknoi, Thailand, 10700
    • Siriraj Hospital
  • Hat Yai, Thailand, 90110
    • Songklanagarind Hospital
  • Rajathevee, Thailand, 10400
    • Pramongkutklao Hospital
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk Nat. Medical University, Dept. Endocrinology
  • Kharkiv, Ukraine, 61039
    • L.T. Malaya Institute of Therapy AMS of Ukraine
  • Kharkiv, Ukraine, 61176
    • CI of Healthcare Kharkiv CCH #8, Kharkiv
  • Kyiv, Ukraine, 03680
    • SI NSC M.D. Strazhesko Institute Cardiology of NAMSU, Kyiv
  • Kyiv, Ukraine, 04114
    • SI D.F.Chebotariov Institute of Gerontology of NAMSU, Kyiv
  • Kyiv, Ukraine, 1601
    • Oleksandrivska Clinical Hospital
  • Poltava, Ukraine, 36011
    • M.V. Sklifosovskyi Poltava RCH, Poltava
  • Vinnytsia, Ukraine, 21018
    • M.I. Pyrogov VRCH, Vinnytsia
  • Vinnytsia, Ukraine, 21029
    • MCIC MC LLC Health Clinic, Vinnytsia
  • Zaporizhzhia, Ukraine, 69600
    • Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group, LLC
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
    • Birmingham, Alabama, United States, 35205
      • Rheumatology Associates
  • Arizona
    • Glendale, Arizona, United States, 85304
      • Arizona Arthritis and Rheumatology Research, PLLC
    • Mesa, Arizona, United States, 85202
      • Arizona Arthritis and Rheumatology Research, PLLC
    • Phoenix, Arizona, United States, 85032-9384
      • Arizona Arthritis and Rheumatology Research, PLLC
    • Phoenix, Arizona, United States, 85037
      • Arizona Arthritis and Rheumatology Research, PLLC
  • California
    • El Cajon, California, United States, 92020-4124
      • TriWest Research Associates, LLC
    • La Palma, California, United States, 90623
      • Advanced Medical Research, LLC
    • Long Beach, California, United States, 90808
      • ProHealth Partners
    • Santa Clara, California, United States, 95051
      • The Permanente Medical Group
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials, Inc.
    • Whittier, California, United States, 90606
      • Medvin Clinical Research
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Alpine Clinical Research Center
  • Florida
    • Boynton Beach, Florida, United States, 33437
      • Orthopedic Research Institute
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida, Inc.
    • Coral Gables, Florida, United States, 33134
      • Universal Clinical Research
    • Jupiter, Florida, United States, 33458
      • Science and Research Institute, Inc.
    • Miami, Florida, United States, 33015
      • San Marcus Research Clinic, Inc.
    • Miami, Florida, United States, 33144
      • L&C Professional Medical Research Institute
    • Pembroke Pines, Florida, United States, 33026
      • Family Clinical Trials, Incorporated
    • South Miami, Florida, United States, 33143
      • Physician Research Collaboration
    • Tamarac, Florida, United States, 33321
      • West Broward Rheumatology Associates, Incorporated
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida, Inc.
    • Tampa, Florida, United States, 33613
      • McIlwain Medical Group, PA
    • Venice, Florida, United States, 34292
      • Lovelace Scientific Resources, Incorporated
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Institute of Arthritis Research
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Goldpoint Clinical Research, LLC
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • The Arthritis & Diabetes Clinic, Incorporated
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Klein and Associates, M.D., P.A.
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • Arthritis Education and Treatment Center
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North MS Medical Clinics, Incorporated
  • Montana
    • Kalispell, Montana, United States, 59901
      • Glacier View Research Institute
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Accurate Clinical Research, Inc.
  • New Jersey
    • Clifton, New Jersey, United States, 07012
      • NJP Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Center for Rheumatology
  • New York
    • Manhasset, New York, United States, 11030
      • Anna Imperato, MD PLLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Box Arthritis & Rheumatology of the Carolinas
    • Greensboro, North Carolina, United States, 27408
      • Medication Management, LLC
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury, LLC
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Ohio
    • Dayton, Ohio, United States, 45417
      • STAT Research, Incorporated
    • Perrysburg, Ohio, United States, 43551
      • Clinical Research Source, Inc.
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research, P.C.
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Mountain View Clinical Research
  • Tennessee
    • Nashville, Tennessee, United States, 37203-2032
      • Center For Inflammatory Disease
  • Texas
    • Austin, Texas, United States, 78731
      • Austin Regional Clinic
    • Corpus Christi, Texas, United States, 78404
      • Adriana Pop Moody Clinic PA
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center
    • Houston, Texas, United States, 77004
      • Accurate Clinical Management LLC
    • Houston, Texas, United States, 77008
      • Pioneer Research Solutions, Inc.
    • Houston, Texas, United States, 77034
      • Accurate Clinical Research, Incorporated
    • Houston, Texas, United States, 77070
      • Rheumatology Clinic of Houston, P.A.
    • Houston, Texas, United States, 77084
      • Accurate Clinical Research, Incorporated
    • Houston, Texas, United States, 77089
      • Houston Rheumatology Consultants, PLLC
    • Lubbock, Texas, United States, 79424
      • Arthritis & Osteoporosis Associates LLP
    • Nassau Bay, Texas, United States, 77058
      • Accurate Clinical Research, Incorporated
    • San Antonio, Texas, United States, 78229
      • Heartland Research Associates, LLC
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Orthopedic Clinic, Incorporated
  • Washington
    • Spokane, Washington, United States, 99204
      • Arthritis Northwest, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• All patients must sign and date an Informed Consent Form consistent with International Conference on Harmonisation Good Clinical Practice (ICH GCP) guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, which include medication washout and restrictions) and be willing to follow the protocol.
• Male or female participants, between 18 and 80 years of age, who have a diagnosis of moderately to severely active Rheumatoid arthritis for at least 6 months as defined by at least six swollen joints (66 joint count) and at least six tender joints (68 joint count) at Screening and Baseline (Day 1), and either an Erythrocyte sedimentation rate of >28 mm/hour OR a C-reactive protein (CRP) level >1.0 mg/dL (normal: <0.4 mg/dL) at Screening. Patients must currently be receiving methotrexate (MTX) therapy.

• Current treatment for Rheumatoid arthritis on an outpatient basis:

  1. Must be receiving and tolerating oral or parenteral MTX therapy at a dose of 15 to 25 mg per week (dose may be as low as 10 mg per week if the patient is unable to tolerate a higher dose) for at least 12 weeks immediately prior to Day 1. The dose and administration route should remain stable for at least 4 weeks prior to Day 1 until Week 24. After Week 24 the administration route can be changed at the investigator's discretion. Patients receiving a lower dose of MTX (10 to 14 mg/week) should be doing so as a result of a documented history of intolerance to higher doses of MTX.
  2. Patients must be willing to receive oral folic acid (at least 5 mg/week or as per local practice) or folinic acid (at least 1 mg/week or as per local practice) or equivalent during the entire trial (mandatory comedication for MTX treatment).
  3. Disease modifying antirheumatic drug (DMARD) use will be restricted according to guidelines listed in the trial protocol.
  4. If receiving current treatment with oral corticosteroids (other than intra-articular or parenteral), the dose must not exceed 10 mg/day prednisolone or equivalent. During the 4 weeks prior to Baseline (Day 1) the dose must remain stable.
  5. Any concomitant non-steroidal anti-inflammatory drugs (NSAIDs) must be stable for at least 2 weeks prior to Day 1.
  6. Patients may be taking oral hydroxychloroquine provided that the dose is not greater than 400 mg/day or chloroquine provided that the dose is not greater than 250 mg/day. These doses must have been stable for a minimum of 12 weeks prior to Day 1. The hydroxychloroquine or chloroquine treatment will need to be continued at a stable dose with the same formulation until the end of the trial.
• For participants of reproductive potential (males and females), a reliable means of contraception has to be used throughout trial participation(acceptable methods of birth control include for example birth control pills, intrauterine devices [IUDs], surgical sterilization, vasectomized partner and double barrier method.. All patients (males and females of child-bearing potential) must also agree to use an acceptable method of contraception for 6 months following completion or discontinuation from the trial medication.

Exclusion criteria:

• ACR functional Class IV or wheelchair/bed bound.
• Primary or secondary immunodeficiency, including known history of HIV infection, or a positive test at Screening.
• History of Tuberculosis, latent Tuberculosis, or positive purified protein derivative test or interferon gamma-releasing assay .
• Known clinically significant coronary artery disease or significant cardiac arrhythmias or severe congestive heart failure, or interstitial lung disease.
• Previous treatment with >=2 biologic agents.
• Previous treatment with adalimumab or adalimumab biosimilar.
• Current treatment or previous treatment with leflunomide within 8 weeks.
• History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to adalimumab or any component of the trial drug.
• History of cancer including solid tumors, hematologic malignancies, and carcinoma in situ.
• Has evidence of positive serology for Hepatitis B virus or Hepatitis C virus
• Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit. Patients who are expecting to receive any live virus or bacterial vaccinations during the trial, or up to 3 months after the last dose of trial drug.
• Any treatment that, in the opinion of the investigator, may place the patient at unacceptable risk during the trial.
• Patients with a significant disease other than Rheumatoid arthritis and/or a significant uncontrolled disease (such as, but not limited to, nervous system, renal, hepatic, endocrine, or gastrointestinal disorders). A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.
• Premenopausal, sexually active women who are pregnant or nursing, or are of child-bearing potential and not practicing an acceptable method of birth control, or do not plan to continue practicing an acceptable method of birth control throughout the trial.
• History of, or current, inflammatory joint disease other than Rheumatoid arthritis or other systemic autoimmune disorder.
• Diagnosis of juvenile idiopathic arthritis, and/or Rheumatoid arthritis before age 16.
• Any planned surgical procedure within 12 weeks prior to the Screening Visit or for the duration of the trial.
• Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with intravenous anti infectives within 4 weeks of the Screening Visit or completion of oral anti-infectives within 2 weeks of the Screening Visit.
• History of deep space/tissue infection within 52 weeks of the Screening Visit.
• History of serious infection or opportunistic infection in the last 2 years.
• Any neurological, vascular or systemic disorder that might affect any of the efficacy assessments.
• Currently active alcohol or drug abuse or history of alcohol or drug abuse within 2 years of the Screening Visit.
• Treatment with intravenous Gamma Globulin or the Prosorba® Column within 6 months of the Screening Visit.
• Treatment with intravenous, intramuscular, intra-articular and parenteral corticosteroids within 6 weeks prior to Day 1 or throughout the trial.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times upper limit of normal.
• Hemoglobin <8.0 g/dL.
• Platelets <100,000/µL.
• Leukocyte count <4000/µL.
• Creatinine clearance <60 mL/min.
• Patients who are currently participating in another clinical trial or who have been participating in another clinical trial with another investigational drug within a minimum of 12 weeks or five half-lives (whichever is longer) of the drug prior to Day 1.
• Patients with a history of any clinically significant adverse reaction to murine or chimeric proteins.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 695501; one injection every 2 weeks for 48 weeks (25 injections in total)	Drug: BI 695501; BI 695501, every two weeks for 48 weeks (25 injections in total)
Active Comparator: US-licensed Humira®; one injection every 2 weeks for 48 weeks (25 injections in total)	Drug: US-licensed Humira®; one injection every 2 weeks for 48 weeks (25 injections in total)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Patients Meeting the American College of Rheumatology 20% (ACR20) Response Criteria at Week 12	The proportion of patients meeting the ACR20 response criteria was assessed. A patient had an ACR20 response if all of the following occurred: A ≥ 20 % improvement in the swollen joint count (66 joints), A ≥ 20 % improvement in the tender joint count (68 joints), A ≥ 20 % improvement in at least three of the following assessments: Patient's assessment of pain, Patient's global assessment of disease activity (equivalent to the General Health component of the Disease Activity Score (DAS)), Physician's global assessment of disease activity, Patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) Acute phase reactant (C-reactive protein (CRP)).The Full Analysis Set contained all enrolled patients who were randomized to trial drug and who received at least one dose of trial drug and had all efficacy measures relevant for the co-primary efficacy endpoints measured at baseline and at least once post- baseline.	Week 12
The Proportion of Patients Meeting ACR20 Response Criteria at Week 24	ACR20 at Week 12 and Week 24 are standard outcome criteria that are widely accepted for regulatory purposes to demonstrate efficacy in treating the signs and symptoms of Rheumatoid arthritis (RA). The proportion of patients meeting the ACR20 response criteria was assessed at Week 12 and Week 24 to provide a robust comparison with US-licensed Humira® data. A patient had an ACR20 response if all of the following occurred: A ≥ 20 % improvement in the swollen joint count (66 joints), A ≥ 20 % improvement in the tender joint count (68 joints), A ≥ 20 % improvement in at least three of the following assessments: Patient's assessment of pain, Patient's global assessment of disease activity (equivalent to the General Health component of the Disease Activity Score ([DAS]), Physician's global assessment of disease activity, Patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) Acute phase reactant (C-reactive protein [CRP]).	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Disease Activity Score 28 (DAS28) (Erythrocyte Sedimentation Rate [ESR]) at Week 12 and Week 24	The DAS28 (ESR) score was derived using the following formulae: DAS28 (ESR) = 0.56*√(TJC28) + 0.28*√(SJC28) + 0.014*(GH) + 0.7*ln(ESR) Where: TJC28 = 28 joint count for tenderness; SJC28 = 28 joint count for swelling; Ln (ESR) = natural logarithm of ESR; GH = General Health component of the DAS (patient's global assessment of disease activity). DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. Actual number of patient analysed (N) is mean number of subjects in the analysis set with DAS28(ESR) results computable across the multiply imputed data sets. It is 319.6, 317.1 for week 12 and 313.9, 315.1 for week 24 for BI 695501 and US-licensed Humira® respectively.	Baseline, Week 12 and Week 24
The Percentage of Patients With Investigator-assessed Drug-related Adverse Events (AEs) During the Treatment Phase	The analysis of AEs was based on the concept of treatment-emergent AEs (TEAEs). Thus, all AEs with an onset after the first dose of trial drug up to a period of ten weeks after the last dose of trial drug were assigned to the current treatment for evaluation. Investigator-assessed drug related AEs were AEs with a relationship to drug ticked "yes" according to the Investigator. Overall results are presented from Day 1 up to Week 58 and are based on the initial randomization groups. The comparison therefore focuses on patients who received BI 695501 continuously versus patients who received Humira® continuously for the long term assessment of safety. One patient was initially treated with Humira and discontinued prior to Week 24. This patient was mistakenly re randomized to BI 695501 but not treated. For safety this was counted in Humira not re-randomized group (as treated), and for other analysis sets, this patient was counted in the Humira to BI 695501 group (as randomized).	From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1.
• Kang J, Eudy-Byrne RJ, Mondick J, Knebel W, Jayadeva G, Liesenfeld KH. Population pharmacokinetics of adalimumab biosimilar adalimumab-adbm and reference product in healthy subjects and patients with rheumatoid arthritis to assess pharmacokinetic similarity. Br J Clin Pharmacol. 2020 Nov;86(11):2274-2285. doi: 10.1111/bcp.14330. Epub 2020 Jun 11.
• Cohen SB, Lee EC. Plain language summary of the VOLTAIRE-RA in patients with moderate-to-severe rheumatoid arthritis. Immunotherapy. 2022 Oct;14(15):1183-1190. doi: 10.2217/imt-2022-0106. Epub 2022 Sep 6. Review.
• Cohen SB, Alonso-Ruiz A, Klimiuk PA, Lee EC, Peter N, Sonderegger I, Assudani D. Similar efficacy, safety and immunogenicity of adalimumab biosimilar BI 695501 and Humira reference product in patients with moderately to severely active rheumatoid arthritis: results from the phase III randomised VOLTAIRE-RA equivalence study. Ann Rheum Dis. 2018 Jun;77(6):914-921. doi: 10.1136/annrheumdis-2017-212245. Epub 2018 Mar 7.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2015
• Primary Completion (Actual): March 3, 2016
• Study Completion (Actual): October 18, 2016

Study Registration Dates

• First Submitted: May 12, 2014
• First Submitted That Met QC Criteria: May 12, 2014
• First Posted (Estimate): May 13, 2014

Study Record Updates

• Last Update Posted (Actual): January 19, 2018
• Last Update Submitted That Met QC Criteria: December 20, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: 1297.2; 2012-002945-40 (EudraCT Number)