Efficacy, Pharmacokinetics, and Safety of BI 695500 in Patients With Rheumatoid Arthritis
- Conditions
- Arthritis, Rheumatoid
- Interventions
- Registration Number
- NCT01682512
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 294
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part I BI 695500 group BI 695500 BI 695500, Two infusions separated by 2 weeks, Intravenous infusion Part I Rituxan® Rituxan® rituximab, Two infusions separated by 2 weeks, Intravenous infusion Part I MabThera® MabThera® rituximab, Two infusions separated by 2 weeks, Intravenous infusion Part II BI 695500 group BI 695500 BI 695500, Two infusions separated by 2 weeks, Intravenous infusion Part II rituximab group Rituxan® rituximab, Two infusions separated by 2 weeks, Intravenous infusion
- Primary Outcome Measures
Name Time Method PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours) 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) 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.
Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I 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) 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 MeanPK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, 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. 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.
- Secondary Outcome Measures
Name Time Method 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. 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).
Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II Week 24 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.
Trial Locations
- Locations (107)
Medication Management, LLC
🇺🇸Greensboro, North Carolina, United States
Adriana Pop Moody Clinic PA
🇺🇸Corpus Christi, Texas, United States
Centro Hospitalar do Baixo Vouga, E.P.E. Unidade de Aveiro
🇵🇹Aveiro, Portugal
Instituto Português de Reumatologia
🇵🇹Lisboa, Portugal
San Diego Arthritis Medical Clinic
🇺🇸San Diego, California, United States
New Horizon Research Center
🇺🇸Miami, Florida, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
MHAT Lyulin
🇧🇬Sofia, Bulgaria
Rheumatology Associates
🇺🇸Birmingham, Alabama, United States
Achieve Clinical Research, LLC
🇺🇸Birmingham, Alabama, United States
Advanced Medical Research, LLC
🇺🇸Lakewood, California, United States
Arthritis &amp; Rheumatology Associates of Palm Beach
🇺🇸Tampa, Florida, United States
ProHealth Partners
🇺🇸Long Beach, California, United States
Columbia Medical Practice, PC
🇺🇸Columbia, Maryland, United States
Inland Rheumatology Clinical Trials, Inc.
🇺🇸Upland, California, United States
Arthritis Associates, Inc.
🇺🇸Orlando, Florida, United States
Westroads Clinical Research
🇺🇸Omaha, Nebraska, United States
International Clinical Research
🇺🇸Overland Park, Kansas, United States
Lovelace Scientific Resources, Incorporated
🇺🇸Venice, Florida, United States
Klein and Associates, M.D., P.A.
🇺🇸Cumberland, Maryland, United States
Clinical Pharmacology Study Group
🇺🇸Worcester, Massachusetts, United States
The Center for Rheumatology and Bone Research
🇺🇸Wheaton, Maryland, United States
West Michigan Rheumatology, PLLC
🇺🇸Grand Rapids, Michigan, United States
Summit Medical Group
🇺🇸Clifton, New Jersey, United States
Office of Dr. Ramesh C. Gupta
🇺🇸Memphis, Tennessee, United States
STAT Research, Incorporated
🇺🇸Dayton, Ohio, United States
Centro de Investigaciones Reumatológicas
🇦🇷San Miguel de Tucuman, Argentina
Organización Médica de Investigación
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Altoona Center for Clinical Research, P.C.
🇺🇸Duncansville, Pennsylvania, United States
MHAT-Plovdiv AD
🇧🇬Plovdiv, Bulgaria
The Seattle Arthritis Clinic, PS
🇺🇸Seattle, Washington, United States
Klinische Forschung Berlin-Buch GmbH, Berlin
🇩🇪Berlin, Germany
Centro Medico Privado de Reumatologia
🇦🇷San Miguel de Tucuman, Argentina
AZ Groeninge - Campus Vercruysselaan
🇧🇪Kortrijk, Belgium
MHAT - Kaspela, EOOD
🇧🇬Plovdiv, Bulgaria
Interin
🇨🇱Santiago, Chile
Instituto Médico CER
🇦🇷Buenos Aires, Argentina
Hospital Britanico de Buenos Aires
🇦🇷Buenos Aires, Argentina
Tacoma Center for Arthritis Research, PS
🇺🇸Tacoma, Washington, United States
Hospital Clínico Pontificia Universidad Católica de Chile
🇨🇱Santiago, Chile
Aviva Medical Clinical Trials Group
🇨🇦Burlington, Ontario, Canada
Antonius Ziekenhuis
🇳🇱Sneek, Netherlands
St Vincent's University Hospital
🇮🇪Dublin, Ireland
Centro de Investigación del Noroeste
🇲🇽Tijuana, Mexico
Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
🇵🇱Bialystok, Poland
Euroclinic of Athens
🇬🇷Athens, Greece
Budai Irgalmasrendi Korhaz KHT.
🇭🇺Budapest, Hungary
Hospital de Jesus
🇲🇽Cuauhtemoc, Mexico
Hospital Universitario de Saltillo
🇲🇽Saltillo, Mexico
Specjalistyczny Osrodek Alergologiczno-Intern. ALL-MED
🇵🇱Krakow, Poland
Linea Corporis Chirurgia Plastyczna Sp. z o. o.
🇵🇱Warszawa, Poland
CI of Healthcare Kharkiv CCH #8, Kharkiv
🇺🇦Kharkiv, Ukraine
Hospital Nuestra Señora de Valme
🇪🇸Sevilla, Spain
Centro Hospitalar do Porto, EPE
🇵🇹Porto, Portugal
Hospital de Sao Teotónio
🇵🇹Viseu, Portugal
MCIC MC LLC Health Clinic, Vinnytsia
🇺🇦Vinnytsia, Ukraine
Whipps Cross University Hospital
🇬🇧London, United Kingdom
Vinnytsia M.I. Pyrogov NMU Ch of internal medicine #3
🇺🇦Vinnytsia, Ukraine
Institute of Arthritis Research
🇺🇸Idaho Falls, Idaho, United States
Arizona Arthritis and Rheumatology Research, PLLC
🇺🇸Phoenix, Arizona, United States
Arizona Arthritis &amp; Rheumatology Associates, P.C.
🇺🇸Glendale, Arizona, United States
Family Clinical Trials, Incorporated
🇺🇸Pembroke Pines, Florida, United States
Avail Clinical Research, LLC
🇺🇸DeLand, Florida, United States
Nascimento, Joao (Private Practice)
🇺🇸Bridgeport, Connecticut, United States
Arthritis Center Medical Group
🇺🇸Santa Maria, California, United States
Westlake Medical Research
🇺🇸Thousand Oaks, California, United States
Premiere Clinical Research, LLC
🇺🇸Lakewood, California, United States
Atlantic Coast Research
🇺🇸Toms River, New Jersey, United States
Albuquerque Center For Rheumatology
🇺🇸Albuquerque, New Mexico, United States
Box Arthritis &amp; Rheumatology of the Carolinas
🇺🇸Charlotte, North Carolina, United States
ClinRX Research LLC
🇺🇸Carrollton, Texas, United States
Center for Inflammatory Disease
🇺🇸Nashville, Tennessee, United States
ClinRx Research LLC
🇺🇸McKinney, Texas, United States
Instituto CAICI
🇦🇷Rosario, Argentina
APRILLUS
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
ZeFOR GmbH
🇩🇪Zerbst, Germany
Centro Medico Prosalud
🇨🇱Santiago, Chile
UMHAT, Clinic of Cardiology, Stara Zagora
🇧🇬Stara Zagora, Bulgaria
SMO.MD GmbH, Magdeburg
🇩🇪Magdeburg, Germany
"Attikon" University General Hospital of Attica
🇬🇷Haidari, Greece
Clinical Research Institute
🇲🇽Tlanepantla, Mexico
Volyn Reg. Center of Cardiovascular Path. and Thrombolysis
🇺🇦Lutsk, Ukraine
Hospital Virgen Macarena
🇪🇸Sevilla, Spain
Lviv Regional Clinical Hospital, Lviv
🇺🇦Lviv, Ukraine
Instituto Ferran de Reumatologia
🇪🇸Barcelona, Spain
Hospital A Coruña
🇪🇸La Coruña, Spain
National Scientific Center Academician M.D. Strazhesko
🇺🇦Kyiv, Ukraine
M.V. Sklifosovskyi Poltava RCH, Poltava
🇺🇦Poltava, Ukraine
M.I. Pyrogov VRCH, Vinnytsia
🇺🇦Vinnytsia, Ukraine
Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia
🇺🇦Zaporizhzhia, Ukraine
Mountain State Clinical Research
🇺🇸Clarksburg, West Virginia, United States
Apex Medical Research
🇺🇸Chicago, Illinois, United States
Rheumatology and Pulmonary Clinic
🇺🇸Beckley, West Virginia, United States
Heartland Research Associates, LLC
🇺🇸Webster, Texas, United States
Arthritis and Osteoporosis Medical Associates, PLLC
🇺🇸Brooklyn, New York, United States
Little Rock Diagnostic Clinic
🇺🇸Little Rock, Arkansas, United States
Medvin Clinical Research
🇺🇸Covina, California, United States
Arthritis Consultants, Inc
🇺🇸Saint Louis, Missouri, United States
TriWest Research Associates, LLC
🇺🇸El Cajon, California, United States
Coeur d'Alene Arthritis Clinical Trials
🇺🇸Coeur d'Alene, Idaho, United States
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Szpital Uniwersytecki nr 2 im.dr J. Biziela
🇵🇱Bydgoszcz, Poland
Wojewodzki Szpital Zespolony w Elblagu
🇵🇱Elblag, Poland
Hospital Fernando Fonseca, EPE
🇵🇹Amadora, Portugal
Wojewodzki Szpital Specjalistyczny we Wroclawiu
🇵🇱Wroclaw, Poland
Hospital Garcia de Orta, EPE
🇵🇹Almada, Portugal
Oleksandrivska Clinical Hospital
🇺🇦Kyiv, Ukraine