Study Stopped
substance discontinued
Efficacy, Pharmacokinetics, and Safety of BI 695500 in Patients With Rheumatoid Arthritis
2 other identifiers
interventional
294
17 countries
110
Brief Summary
The primary objectives of this trial are (1) To show PK (Pharmacokinetic) similarity of BI 695500 to rituximab. (2)To establish statistical equivalence of efficacy of BI 695500 and rituximab, in patients with moderately to severely active RA (Rheumatoid Arthritis), based on the change in Disease Activity Score 28 (DAS28) score measured at 24 weeks compared to Baseline and the American College of Rheumatology 20% (ACR20) response rate at Week 24.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2012
Typical duration for phase_3
110 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 10, 2012
CompletedStudy Start
First participant enrolled
September 5, 2012
CompletedFirst Posted
Study publicly available on registry
September 11, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 17, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
October 12, 2016
CompletedResults Posted
Study results publicly available
January 30, 2018
CompletedJanuary 30, 2018
January 1, 2018
3.2 years
August 10, 2012
October 24, 2017
January 4, 2018
Conditions
Outcome Measures
Primary Outcomes (5)
Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I
The DAS28 score was derived using the formula: DAS28 (ESR) = 0.56\*√(TJC28) + 0.28\*√(SJC28) + 0.70\*ln(ESR) + 0.014\*(GH), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the General Health component of the DAS \[score on a visual analogue scale (VAS) ranging from 0 (very well) to 100 (very poor)\]. DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. Low disease activity is defined as a DAS28 score of ≤ 3.2 and DAS28 remission is defined as a DAS28 score of \< 2.6. A clinically important change in DAS28 score is defined as an improvement in DAS28 score of at least 1.2. The full analysis set (FAS) contained all randomized subjects who received at least one dose of trial medication, had at least one assessment of primary efficacy endpoint at Baseline and at post-baseline visit prior or at Week 24 visit.
Baseline and Week 24
PK (Part I Only): AUC0-tz (Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration, Determined Over Both Dosages)
Pharmacokinetic (PK) (Part I only): AUC0-tz (area under the plasma concentration versus time curve from time zero to the last measurable concentration, determined over both dosages). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. As per protocol all the following criteria had to be fulfilled for a patient to be defined as PK evaluable for the Pharmacokinetic analysis set (PKS): Full first and second dose given. Pre-dose concentration available prior to the second dose. Ability to estimate AUC during the infusion phases. Ability to estimate the AUC for the distribution phase after the second dose. Ability to estimate the terminal half-life (t1/2) after the second dose. gMean - Geometric Mean
Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
PK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Determined Over Both Dosages)
PK (Part I only): AUC0-inf pred (area under the plasma concentration versus time curve from time zero to infinity, determined over both dosages, and extrapolated to infinity using predicted last observed quantifiable concentration). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.
Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours)
PK (Part I only): AUC0-336 (area under the plasma concentration versus time curve from time zero to 336 hours after the first dose). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.
Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
PK (Part I Only): Observed Cmax (Maximum Plasma Concentration, Determined After the Second Dose)
PK (Part I only): observed Cmax (observed maximum plasma concentration, determined after the second dose). Only subjects randomized in part I of this study are included.
Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
Secondary Outcomes (2)
Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II
Week 24
PK (Part I Only): AUC0-inf, Ppk (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Based on Individual Predicted Concentrations for Missing Data Derived From a Population PK Model, Determined Over Both Dosages)
Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
Study Arms (5)
Part I BI 695500 group
EXPERIMENTALBI 695500, Two infusions separated by 2 weeks, Intravenous infusion
Part I Rituxan®
ACTIVE COMPARATORrituximab, Two infusions separated by 2 weeks, Intravenous infusion
Part I MabThera®
ACTIVE COMPARATORrituximab, Two infusions separated by 2 weeks, Intravenous infusion
Part II BI 695500 group
EXPERIMENTALBI 695500, Two infusions separated by 2 weeks, Intravenous infusion
Part II rituximab group
ACTIVE COMPARATORrituximab, Two infusions separated by 2 weeks, Intravenous infusion
Interventions
Eligibility Criteria
You may qualify if:
- Must give written informed consent 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 RA for at least 6 months as defined by at least six swollen joints (66 joint count) and at least eight tender joints (68 joint count) at Screening and Baseline (Day 1), and either an erythrocyte sedimentation rate (ESR) of \> 28 mm/hour OR a C-reactive protein (CRP) level \> 1.0 mg/dL (normal: \< 0.4 mg/dL) at Screening. Patients must have had an inadequate response or intolerance to conventional DMARD therapy including at least one tumor necrosis factor (TNF) inhibitor.
- Positive for Radio Frequency and/or anti-CCP (Anti-cyclic citrullinated peptide) antibodies.
- Current treatment for RA on an outpatient basis:
- Must be currently receiving and tolerating oral or parenteral MTX therapy at a dose of 15-25 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 should be 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 must be willing to receive oral folic acid (at least 5 mg/week or as per local practice) or equivalent during the entire study (mandatory co-medication for MTX treatment).
- Biologic agents and DMARDs (other than MTX) must be withdrawn at least 2 weeks prior to Day 1, except azathioprine and etanercept which must be withdrawn at least 4 weeks prior to Day 1; abatacept, adalimumab, anakinra, certolizumab, infliximab, and golimumab at least 8 weeks prior to Day 1; tocilizumab at least 10 weeks prior to Day 1.
- Leflunomide must be withdrawn at least 8 weeks prior to Day 1 or a minimum of 2 weeks prior to Day 1 if after 11 days of standard cholestyramine washout.
- 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.
- Intra-articular and parenteral corticosteroids are not permitted within 6 weeks prior to Baseline Day 1 or throughout the trial, with the exception of IV administration of 100 mg methylprednisolone 30 to 60 minutes prior to each infusion as this is part of the trial procedures.
- Any concomitant non-steroidal anti-inflammatory drugs (NSAIDs) must be stable for at least 2 weeks prior to Day 1.
- 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), use of a reliable means of contraception (e.g., hormonal contraceptive, patch, intrauterine device, physical barrier) has to be used throughout trial participation. Females of child-bearing potential must also agree to use an acceptable method of contraception for 12 months following completion or discontinuation from the trial.
You may not qualify if:
- ACR functional Class IV or wheelchair/bed bound.
- Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus infection.
- History of positive purified protein derivative test (positive tuberculosis \[TB\] test) without treatment for TB infection or chemoprophylaxis for TB exposure.
- Positive HIV or TB at screening.
- Known coronary artery disease or significant cardiac arrhythmias or severe congestive heart failure (New York Heart Association classes III or IV), or interstitial lung disease observed on chest X-ray.
- History of IgE-mediated (immunoglobulin E) or non-IgE-mediated hypersensitivity or known anaphylaxis to mouse proteins or a history of hypersensitivity to antibody therapy.
- History of cancer including solid tumors, hematologic malignancies, and carcinoma in situ (except participants with previous resected and cured basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ Grade I cervical cancer within 5 years prior to the Screening Visit).
- History of pancreatitis or current peptic ulcer disease.
- Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit.
- Any condition or treatment (including biologic therapies) that, in the opinion of the investigator, may place the patient at unacceptable risk during the trial.
- Pregnancy or breast feeding.
- History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, pulmonary fibrosis, or Feltys syndrome, scleroderma, inflammatory myopathy, mixed connective tissue disease, or any overlap syndrome).
- Diagnosis of juvenile idiopathic arthritis, also known as juvenile RA, and/or RA before age 16.
- Any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to the Screening Visit or planned within 24 weeks of the Screening Visit.
- Lack of peripheral venous access.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (110)
Rheumatology Associates
Birmingham, Alabama, 35205, United States
Achieve Clinical Research, LLC
Birmingham, Alabama, 35216, United States
Arizona Arthritis &amp; Rheumatology Associates, P.C.
Glendale, Arizona, 85304, United States
Arizona Arthritis and Rheumatology Research, PLLC
Mesa, Arizona, 85032, United States
Arizona Arthritis and Rheumatology Research, PLLC
Mesa, Arizona, 85202, United States
Arizona Arthritis and Rheumatology Research, PLLC
Phoenix, Arizona, 85307, United States
Little Rock Diagnostic Clinic
Little Rock, Arkansas, 72205, United States
Medvin Clinical Research
Covina, California, 91723, United States
TriWest Research Associates, LLC
El Cajon, California, 92020, United States
Advanced Medical Research, LLC
Lakewood, California, 90712, United States
Premiere Clinical Research, LLC
Lakewood, California, 90712, United States
ProHealth Partners
Long Beach, California, 90808, United States
San Diego Arthritis Medical Clinic
San Diego, California, 92108, United States
Arthritis Center Medical Group
Santa Maria, California, 93454, United States
Westlake Medical Research
Thousand Oaks, California, 91360, United States
Inland Rheumatology Clinical Trials, Inc.
Upland, California, 91786, United States
Nascimento, Joao (Private Practice)
Bridgeport, Connecticut, 06606, United States
Avail Clinical Research, LLC
DeLand, Florida, 32720, United States
New Horizon Research Center
Miami, Florida, 33175, United States
Arthritis Associates, Inc.
Orlando, Florida, 32804, United States
Family Clinical Trials, Incorporated
Pembroke Pines, Florida, 33026, United States
Arthritis &amp; Rheumatology Associates of Palm Beach
Tampa, Florida, 33609, United States
Lovelace Scientific Resources, Incorporated
Venice, Florida, 34292, United States
Coeur d'Alene Arthritis Clinical Trials
Coeur d'Alene, Idaho, 83814, United States
Institute of Arthritis Research
Idaho Falls, Idaho, 83404, United States
Apex Medical Research
Chicago, Illinois, 60616, United States
International Clinical Research
Overland Park, Kansas, 66210, United States
Columbia Medical Practice, PC
Columbia, Maryland, 21045, United States
Klein and Associates, M.D., P.A.
Cumberland, Maryland, 21502, United States
The Center for Rheumatology and Bone Research
Wheaton, Maryland, 20902, United States
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01605, United States
West Michigan Rheumatology, PLLC
Grand Rapids, Michigan, 49546, United States
Arthritis Consultants, Inc
St Louis, Missouri, 63141, United States
Westroads Clinical Research
Omaha, Nebraska, 68114, United States
Summit Medical Group
Clifton, New Jersey, 07012, United States
Atlantic Coast Research
Toms River, New Jersey, 08755, United States
Albuquerque Center For Rheumatology
Albuquerque, New Mexico, 87102, United States
Arthritis and Osteoporosis Medical Associates, PLLC
Brooklyn, New York, 11201, United States
Box Arthritis &amp; Rheumatology of the Carolinas
Charlotte, North Carolina, 28210, United States
Medication Management, LLC
Greensboro, North Carolina, 27408, United States
STAT Research, Incorporated
Dayton, Ohio, 45417, United States
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112, United States
Altoona Center for Clinical Research, P.C.
Duncansville, Pennsylvania, 16635, United States
Office of Dr. Ramesh C. Gupta
Memphis, Tennessee, 38119, United States
Center for Inflammatory Disease
Nashville, Tennessee, 37203, United States
ClinRX Research LLC
Carrollton, Texas, 75007, United States
Adriana Pop Moody Clinic PA
Corpus Christi, Texas, 78404, United States
Heartland Research Associates, LLC
Houston, Texas, 77034, United States
ClinRx Research LLC
McKinney, Texas, 75069, United States
Heartland Research Associates, LLC
Webster, Texas, 77598, United States
The Seattle Arthritis Clinic, PS
Seattle, Washington, 98133, United States
Tacoma Center for Arthritis Research, PS
Tacoma, Washington, 98405-2395, United States
Rheumatology and Pulmonary Clinic
Beckley, West Virginia, 25801, United States
Mountain State Clinical Research
Clarksburg, West Virginia, 26301, United States
Instituto Médico CER
Buenos Aires, B1878DVB, Argentina
Hospital Britanico de Buenos Aires
Buenos Aires, C1289AEB, Argentina
Organización Médica de Investigación
Ciudad Autonoma Buenos Aires, C1015ABO, Argentina
APRILLUS
Ciudad Autonoma Buenos Aires, C1194AAN, Argentina
Instituto CAICI
Rosario, S2000PBJ, Argentina
Centro de Investigaciones Reumatológicas
San Miguel de Tucumán, 4000, Argentina
Centro Medico Privado de Reumatologia
San Miguel de Tucumán, T4000AXL, Argentina
AZ Groeninge - Campus Vercruysselaan
Kortrijk, 8500, Belgium
MHAT - Kaspela, EOOD
Plovdiv, 4002, Bulgaria
MHAT-Plovdiv AD
Plovdiv, 4002, Bulgaria
MHAT Lyulin
Sofia, 1336, Bulgaria
UMHAT, Clinic of Cardiology, Stara Zagora
Stara Zagora, 6000, Bulgaria
Aviva Medical Clinical Trials Group
Burlington, Ontario, L7R 2H7, Canada
Interin
Santiago, 7500010, Chile
Centro Medico Prosalud
Santiago, 7510047, Chile
Hospital Clínico Pontificia Universidad Católica de Chile
Santiago, 8330033, Chile
Klinische Forschung Berlin-Buch GmbH, Berlin
Berlin, 13125, Germany
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, 1307, Germany
SMO.MD GmbH, Magdeburg
Magdeburg, 39112, Germany
ZeFOR GmbH
Zerbst, 39261, Germany
Euroclinic of Athens
Athens, 15121, Greece
"Attikon" University General Hospital of Attica
Haidari, 12462, Greece
Budai Irgalmasrendi Korhaz KHT.
Budapest, 1027, Hungary
St Vincent's University Hospital
Dublin, 4, Ireland
Hospital de Jesus
Cuauhtémoc, 6090, Mexico
Hospital Universitario de Saltillo
Saltillo, 25000, Mexico
Centro de Investigación del Noroeste
Tijuana, 22010, Mexico
Clinical Research Institute
Tlanepantla, 54055, Mexico
Antonius Ziekenhuis
Sneek, 8601 ZK, Netherlands
Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
Bialystok, 15-099, Poland
Szpital Uniwersytecki nr 2 im.dr J. Biziela
Bydgoszcz, 85-168, Poland
Wojewodzki Szpital Zespolony w Elblagu
Elblag, 82-300, Poland
Specjalistyczny Osrodek Alergologiczno-Intern. ALL-MED
Krakow, 31-023, Poland
Linea Corporis Chirurgia Plastyczna Sp. z o. o.
Warsaw, 02-653, Poland
Wojewodzki Szpital Specjalistyczny we Wroclawiu
Wroclaw, 52-224, Poland
Hospital Garcia de Orta, EPE
Almada, 2801-951, Portugal
Hospital Fernando Fonseca, EPE
Amadora, 2720-276, Portugal
Centro Hospitalar do Baixo Vouga, E.P.E. Unidade de Aveiro
Aveiro, 3814-501, Portugal
Instituto Português de Reumatologia
Lisbon, 1050-034, Portugal
Centro Hospitalar do Porto, EPE
Porto, 4099-001, Portugal
Hospital de Sao Teotónio
Viseu, 3504-509, Portugal
Hospital A Coruña
A Coruña, 15006, Spain
Instituto Ferran de Reumatologia
Barcelona, 08034, Spain
Hospital Virgen Macarena
Seville, 41009, Spain
Hospital Nuestra Señora de Valme
Seville, 41014, Spain
CI of Healthcare Kharkiv CCH #8, Kharkiv
Kharkiv, 61176, Ukraine
Oleksandrivska Clinical Hospital
Kyiv, 01601, Ukraine
National Scientific Center Academician M.D. Strazhesko
Kyiv, 3680, Ukraine
Volyn Reg. Center of Cardiovascular Path. and Thrombolysis
Lutsk, 43024, Ukraine
Lviv Regional Clinical Hospital, Lviv
Lviv, 79010, Ukraine
M.V. Sklifosovskyi Poltava RCH, Poltava
Poltava, 36011, Ukraine
M.I. Pyrogov VRCH, Vinnytsia
Vinnytsia, 21018, Ukraine
MCIC MC LLC Health Clinic, Vinnytsia
Vinnytsia, 21029, Ukraine
Vinnytsia M.I. Pyrogov NMU Ch of internal medicine #3
Vinnytsia, 21029, Ukraine
Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia
Zaporizhzhia, 69600, Ukraine
Whipps Cross University Hospital
London, E11 1NR, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study program was terminated and this study was discontinued on 3 September 2015. As a result no patients receiving study treatment in Part II of the study reached Week 24, and no conclusions regarding the efficacy of BI 695500 can be made.
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Center
- Organization
- Boehringer Ingelheim
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 10, 2012
First Posted
September 11, 2012
Study Start
September 5, 2012
Primary Completion
November 17, 2015
Study Completion
October 12, 2016
Last Updated
January 30, 2018
Results First Posted
January 30, 2018
Record last verified: 2018-01