Arthritis, RheumatoidPhase 3NCT01682512
Efficacy, Pharmacokinetics, and Safety of BI 695500 in Patients With Rheumatoid Arthritis
A Phase 3 study testing BI 695500, Rituxan® and MabThera® in people with Arthritis, Rheumatoid, run by Boehringer Ingelheim at 110 sites in 17 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Arthritis, Rheumatoid
- What is being tested?
- BI 695500, Rituxan® and MabThera®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 294 participants
- Where
- 110 sitesin 17 countries
- Study dates
- 5 Sep 2012to 12 Oct 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
- Evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine, or gastrointestinal disorders which, in the investigator's opinion, would preclude patient participation.
- Known concurrent viral hepatitis or known positivity to HBe-ag, HBV DNA, HBV DNA polymerase, HCVRNA, anti HCV antibodies.
- Known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV 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 (e.g., fasciitis, abscess, osteomyelitis) within 52 weeks of the Screening Visit.
- History of serious infection or opportunistic infection in the last 2 years.
- Any neurological (congenital or acquired), vascular or systemic disorder that might affect any of the efficacy assessments, in particular, joint pain and swelling (e.g., Parkinson's disease, cerebral palsy, diabetic neuropathy).
- Currently active alcohol or drug abuse or history of alcohol or drug abuse (as determined by the investigator) within 52 weeks of the Screening Visit.
- Treatment with IV Gamma Globulin or the Prosorba® Column within 6 months of the Screening Visit.
- Treatment with IV or intramuscular corticosteroids.
- Previous treatment with a B cell modulating or cell depleting therapy.
- Intolerance or contraindications to IV glucocorticoids.
- AST (aspartate aminotransferase) or ALT (alanine aminotransferase)> 3 times ULN (Upper Limit of Normal)
- Hemoglobin < 8.0 g/dL.
- Levels of IgG < 5.0 g/L.
- Absolute neutrophil count < 1500/µL.
- Platelet count < 75000/µL.
- Participation in any previous clinical trial within 12 weeks of Screening.
Trial locations and contacts
110 sites in 17 countries.
110 sites in 17 countries
United States54 sites
Albuquerque Center For Rheumatology
Albuquerque, New Mexico, 87102
Rheumatology and Pulmonary Clinic
Beckley, West Virginia, 25801
Rheumatology Associates
Birmingham, Alabama, 35205
Achieve Clinical Research, LLC
Birmingham, Alabama, 35216
Nascimento, Joao (Private Practice)
Bridgeport, Connecticut, 06606
Arthritis and Osteoporosis Medical Associates, PLLC
Brooklyn, New York, 11201
ClinRX Research LLC
Carrollton, Texas, 75007
Box Arthritis &amp; Rheumatology of the Carolinas
Charlotte, North Carolina, 28210
Apex Medical Research
Chicago, Illinois, 60616
Mountain State Clinical Research
Clarksburg, West Virginia, 26301
Summit Medical Group
Clifton, New Jersey, 07012
Coeur d'Alene Arthritis Clinical Trials
Coeur d'Alene, Idaho, 83814
Columbia Medical Practice, PC
Columbia, Maryland, 21045
Adriana Pop Moody Clinic PA
Corpus Christi, Texas, 78404
Medvin Clinical Research
Covina, California, 91723
Klein and Associates, M.D., P.A.
Cumberland, Maryland, 21502
STAT Research, Incorporated
Dayton, Ohio, 45417
Avail Clinical Research, LLC
DeLand, Florida, 32720
Altoona Center for Clinical Research, P.C.
Duncansville, Pennsylvania, 16635
TriWest Research Associates, LLC
El Cajon, California, 92020
Arizona Arthritis &amp; Rheumatology Associates, P.C.
Glendale, Arizona, 85304
West Michigan Rheumatology, PLLC
Grand Rapids, Michigan, 49546
Medication Management, LLC
Greensboro, North Carolina, 27408
Heartland Research Associates, LLC
Houston, Texas, 77034
Institute of Arthritis Research
Idaho Falls, Idaho, 83404
Advanced Medical Research, LLC
Lakewood, California, 90712
Premiere Clinical Research, LLC
Lakewood, California, 90712
Little Rock Diagnostic Clinic
Little Rock, Arkansas, 72205
ProHealth Partners
Long Beach, California, 90808
ClinRx Research LLC
McKinney, Texas, 75069
Office of Dr. Ramesh C. Gupta
Memphis, Tennessee, 38119
Arizona Arthritis and Rheumatology Research, PLLC
Mesa, Arizona, 85032
Arizona Arthritis and Rheumatology Research, PLLC
Mesa, Arizona, 85202
New Horizon Research Center
Miami, Florida, 33175
Center for Inflammatory Disease
Nashville, Tennessee, 37203
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112
Westroads Clinical Research
Omaha, Nebraska, 68114
Arthritis Associates, Inc.
Orlando, Florida, 32804
International Clinical Research
Overland Park, Kansas, 66210
Family Clinical Trials, Incorporated
Pembroke Pines, Florida, 33026
Arizona Arthritis and Rheumatology Research, PLLC
Phoenix, Arizona, 85307
San Diego Arthritis Medical Clinic
San Diego, California, 92108
Arthritis Center Medical Group
Santa Maria, California, 93454
The Seattle Arthritis Clinic, PS
Seattle, Washington, 98133
Arthritis Consultants, Inc
St Louis, Missouri, 63141
Tacoma Center for Arthritis Research, PS
Tacoma, Washington, 98405-2395
Arthritis &amp; Rheumatology Associates of Palm Beach
Tampa, Florida, 33609
Westlake Medical Research
Thousand Oaks, California, 91360
Atlantic Coast Research
Toms River, New Jersey, 08755
Inland Rheumatology Clinical Trials, Inc.
Upland, California, 91786
Lovelace Scientific Resources, Incorporated
Venice, Florida, 34292
Heartland Research Associates, LLC
Webster, Texas, 77598
The Center for Rheumatology and Bone Research
Wheaton, Maryland, 20902
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01605
Ukraine10 sites
CI of Healthcare Kharkiv CCH #8, Kharkiv
Kharkiv, 61176
Oleksandrivska Clinical Hospital
Kyiv, 01601
National Scientific Center Academician M.D. Strazhesko
Kyiv, 3680
Volyn Reg. Center of Cardiovascular Path. and Thrombolysis
Lutsk, 43024
Lviv Regional Clinical Hospital, Lviv
Lviv, 79010
M.V. Sklifosovskyi Poltava RCH, Poltava
Poltava, 36011
M.I. Pyrogov VRCH, Vinnytsia
Vinnytsia, 21018
MCIC MC LLC Health Clinic, Vinnytsia
Vinnytsia, 21029
Vinnytsia M.I. Pyrogov NMU Ch of internal medicine #3
Vinnytsia, 21029
Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia
Zaporizhzhya, 69600
Argentina7 sites
Instituto Médico CER
Buenos Aires, B1878DVB
Hospital Britanico de Buenos Aires
Buenos Aires, C1289AEB
Organización Médica de Investigación
Ciudad Autonoma Buenos Aires, C1015ABO
APRILLUS
Ciudad Autonoma Buenos Aires, C1194AAN
Instituto CAICI
Rosario, S2000PBJ
Centro de Investigaciones Reumatológicas
San Miguel de Tucumán, 4000
Centro Medico Privado de Reumatologia
San Miguel de Tucumán, T4000AXL
Poland6 sites
Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
Bialystok, 15-099
Szpital Uniwersytecki nr 2 im.dr J. Biziela
Bydgoszcz, 85-168
Wojewodzki Szpital Zespolony w Elblagu
Elblag, 82-300
Specjalistyczny Osrodek Alergologiczno-Intern. ALL-MED
Krakow, 31-023
Linea Corporis Chirurgia Plastyczna Sp. z o. o.
Warsaw, 02-653
Wojewodzki Szpital Specjalistyczny we Wroclawiu
Wroclaw, 52-224
Portugal6 sites
Hospital Garcia de Orta, EPE
Almada, 2801-951
Hospital Fernando Fonseca, EPE
Amadora, 2720-276
Centro Hospitalar do Baixo Vouga, E.P.E. Unidade de Aveiro
Aveiro, 3814-501
Instituto Português de Reumatologia
Lisbon, 1050-034
Centro Hospitalar do Porto, EPE
Porto, 4099-001
Hospital de Sao Teotónio
Viseu, 3504-509
Bulgaria4 sites
MHAT - Kaspela, EOOD
Plovdiv, 4002
MHAT-Plovdiv AD
Plovdiv, 4002
MHAT Lyulin
Sofia, 1336
UMHAT, Clinic of Cardiology, Stara Zagora
Stara Zagora, 6000
Germany4 sites
Klinische Forschung Berlin-Buch GmbH, Berlin
Berlin, 13125
Universitätsklinikum Carl Gustav Carus Dresden
Dresden, 1307
SMO.MD GmbH, Magdeburg
Magdeburg, 39112
ZeFOR GmbH
Zerbst, 39261
Mexico4 sites
Hospital de Jesus
Cuauhtémoc, 6090
Hospital Universitario de Saltillo
Saltillo, 25000
Centro de Investigación del Noroeste
Tijuana, 22010
Clinical Research Institute
Tlanepantla, 54055
Spain4 sites
Hospital A Coruña
A Coruña, 15006
Instituto Ferran de Reumatologia
Barcelona, 08034
Hospital Virgen Macarena
Seville, 41009
Hospital Nuestra Señora de Valme
Seville, 41014
Chile3 sites
Interin
Santiago, 7500010
Centro Medico Prosalud
Santiago, 7510047
Hospital Clínico Pontificia Universidad Católica de Chile
Santiago, 8330033
Greece2 sites
Euroclinic of Athens
Athens, 15121
"Attikon" University General Hospital of Attica
Haidari, 12462
About this study
Official title: Efficacy, Pharmacokinetics, and Safety of BI 695500 Versus Rituximab in Patients With Moderately to Severely Active Rheumatoid Arthritis: a Randomized, Double-blind, Parallel Arm, Multiple Dose, Active Comparator Trial.
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.
- Conditions
- Arthritis, Rheumatoid
- Being tested
- BI 695500, Rituxan®, MabThera®
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 695500Drug
BI 695500Drug
Rituxan®Drug
Rituxan®Drug
MabThera®Drug
| Study group | Role | What they receive |
|---|---|---|
| Part I BI 695500 group | Experimental | BI 695500, Two infusions separated by 2 weeks, Intravenous infusion Receives: Drug: BI 695500 |
| Part I Rituxan® | Active comparator | rituximab, Two infusions separated by 2 weeks, Intravenous infusion Receives: Drug: Rituxan® |
| Part I MabThera® | Active comparator | rituximab, Two infusions separated by 2 weeks, Intravenous infusion Receives: Drug: MabThera® |
| Part II BI 695500 group | Experimental | BI 695500, Two infusions separated by 2 weeks, Intravenous infusion Receives: Drug: BI 695500 |
| Part II rituximab group | Active comparator | rituximab, Two infusions separated by 2 weeks, Intravenous infusion Receives: Drug: Rituxan® |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
A subject has an ACR20 response if all of the following occur:
- 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 3 of the following assessments: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index, or Acute phase reactant (C-reactive protein).
The percentage of subjects meeting the ACR20 response criteria at Week 24 (part-I and II) is presented for subjects randomised to receive BI 695500, Rituxan and MabThera.
Measured: 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)
PK (Part I only): AUC0-inf, ppk. Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. A modeling approach was used to impute missing values as well as impute missing concentrations after the first dose with a sampling schedule identical to the first 2 weeks after the second dose. A unit dose of 1000 mg was used in calculating the imputed values. The resulting dataset thus consisted of PK evaluable and PK non-evaluable patients with both measured as well as imputed concentration values. The prediction of these concentrations was based on a mixed effect modeling approach and included significant covariates as identified during the PK model development (including age, body surface area [BSA], body mass index [BMI], weight, gender, race, and formulation).
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2012 (estimated)
- Study start5 Sep 2012
- Primary completion17 Nov 2015
- Study completion12 Oct 2016
Why it stopped: substance discontinued
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 294 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01682512
- Sponsor's protocol ID
- 1301.1
- Other IDs
- 2011-002894-48
- Status last verified
- Jan 2018
- First submitted
- 10 Aug 2012
- Last updated
- 30 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Pharmacokinetics, and Safety of BI 695500 Versus Rituximab in Patients With Moderately to Severely Active Rheumatoid Arthritis: a Randomized, Double-blind, Parallel Arm, Multiple Dose, Active Comparator Trial.
- ClinicalTrials.gov ID
- NCT01682512
- Acronym / sponsor ID
- 1301.1
- Conditions
- Arthritis, Rheumatoid
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: substance discontinued
- Enrolment
- 294 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 5 Sep 2012 (actual)
- Primary completion
- 17 Nov 2015 (actual)
- Study completion
- 12 Oct 2016 (actual)
- First posted
- 11 Sep 2012 (estimated)
- Results
- Posted 30 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part I BI 695500 group | Experimental | Drug: BI 695500BI 695500, Two infusions separated by 2 weeks, Intravenous infusion |
| Part I Rituxan® | Active comparator | Drug: Rituxan®rituximab, Two infusions separated by 2 weeks, Intravenous infusion |
| Part I MabThera® | Active comparator | Drug: MabThera®rituximab, Two infusions separated by 2 weeks, Intravenous infusion |
| Part II BI 695500 group | Experimental | Drug: BI 695500BI 695500, Two infusions separated by 2 weeks, Intravenous infusion |
| Part II rituximab group | Active comparator | Drug: Rituxan®rituximab, Two infusions separated by 2 weeks, Intravenous infusion |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- 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.
Key exclusion criteria (32 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BI 695500 | Drug | Part II BI 695500 group |
| BI 695500 | Drug | Part I BI 695500 group |
| Rituxan® | Drug | Part I Rituxan® |
| Rituxan® | Drug | Part II rituximab group |
| MabThera® | Drug | Part I MabThera® |
Primary outcome
Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I
Time frame: Baseline and Week 24
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.
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 frame: 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.
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
PK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Determined Over Both Dosages)
Time frame: 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, 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.
PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours)
Time frame: 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 after the first dose). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.
PK (Part I Only): Observed Cmax (Maximum Plasma Concentration, Determined After the Second Dose)
Time frame: 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 (observed maximum plasma concentration, determined after the second dose). Only subjects randomized in part I of this study are included.
2 secondary outcomes
Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II
Time frame: 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)
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Synopsis LinkLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
110 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BI 695500, Rituxan® and MabThera® in people with Arthritis, Rheumatoid, run by Boehringer Ingelheim at 110 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 110 sites in United States, Ukraine, Argentina, Poland, Portugal and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I (time frame: Baseline and Week 24). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2018; AzTrials last refreshed its copy on 8 Nov 2026.