Clinical trial NCT02640612: Long-term Assessment of Safety and Efficacy of BI 695501 in Patients With Rheumatoid Arthritis
Official title: Long-term Assessment of Safety, Efficacy, Pharmacokinetics and Immunogenicity of BI 695501 in Patients With Rheumatoid Arthritis (RA): an Open-label Extension Trial for Patients Who Have Completed Trial 1297.2 and Are Eligible for Long-term Treatment With Adalimumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2015-12-29
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective of this trial is to provide long-term safety, pharmacokinetics (PK), and immunogenicity data on BI 695501 administered via prefilled syringe in patients with Rheumatoid Arthritis who have completed Trial 1297.2. The primary endpoint thereby is the number (proportion) of patients with drug-related adverse events (AEs) during the treatment phase. The secondary objective in this trial is the assessment of Long-term efficacy of BI 695501 by evaluation of:

* the change from Baseline in DAS28 (ESR) at Week 48
* the proportion of patients meeting American College of Rheumatology 20% (ACR20) response criteria at Week 48
* the proportion of patients who meet the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) definition of remission at Week 48
* the proportion of patients with EULAR response (good response, moderate response, or no response) at Week 48.


Eligibility criteria: Inclusion criteria:

* All patients must sign and date an Informed Consent Form consistent withInternational Conference on Harmonisation (ICH) Good Clinical Practice (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.
* Adult patients with moderately to severely active RA who have completed Trial 1297.2, and who wish to participate in this extension trial and in the investigator´s assessment can benefit from receiving BI 695501.
* Patients willing and able to self-administer BI 695501 pre-filled syringe.
* Willing to use a reliable means of contraception throughout trial participation (females) and willing to use an acceptable method of contraception for 6 months following completion or discontinuation from the trial medication males and females).

Exclusion criteria:

* Investigator-reported drug-related Serious Adverse Events (SAEs) in Trial 1297.2
* ACR functional Class IV or wheelchair/bed bound
* Primary or secondary immunodeficiency (history of, or currently active)
* Positive QuantiFERON test
* Known clinically significant coronary artery disease or significant cardiac arrhythmias or severe congestive heart failure (NYHA Classes III / IV), or interstitial lung disease
* Anaphylactic reaction or hypersensitivity to adalimumab in Trial 1297.2
* History / recent evidence of cancer incl. solid tumours, hematologic malignancies, and carcinoma in situ (certain exceptions permitted)
* Positive serology for Hepatitis B virus (HBV) or Hepatitis C virus (HCV)
* Planned live virus or bacterial vaccinations during the trial, or up to 3 months after the last dose of trial drug
* Receipt or treatment (including biologic therapies) that may place the patient at unacceptable risk during the trial
* Significant disease (disease which may (i) put the patient at risk because of participation or (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial) other than RA and/or a significant uncontrolled disease
* Women: premenopausal (last menstruation 1 year prior to screening), sexually active, pregnant or nursing, or of child-bearing potential and not practicing an acceptable method of birth control, or not planning to use an acceptable method of birth control throughout the trial
* Current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, etc.) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, pulmonary fibrosis, etc.). Secondary Sjögren´s syndrome or secondary limited cutaneous vasculitis with RA is permitted
* Any planned surgical procedure, including bone/joint surgery/synovectomy 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 iv. anti-infectives within 4 weeks of the Screening Visit or completion of oral anti-infectives within 2 weeks of the Screening Visit
* Serious infection or opportunistic infection during the 1297.2 trial
* Any acquired neurological, vascular, systemic or demyelinating disorder that might affect any of the efficacy assessments, in particular, joint pain and swelling (e.g., Parkinson´s disease, cerebral palsy, diabetic neuropathy) that occurred during the 1297.2 trial.
* Currently active alcohol or drug abuse
* Treatment with iv. Gamma Globulin or the Prosorba® Column during the 1297.2 trial
* Planned treatment with iv. intramuscular, intra-articular and parenteral corticosteroids
* Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>1.5 times upper limit of normal (ULN)
* Hemoglobin \<8.0 g/dL
* Platelets \<100,000/µL
* Leukocyte count \<4000/µL
* Creatine clearance \<60 mL/min
* Current participation in another clinical trial

Primary outcomes:
measure: Percentage of Patients With Drug-related Adverse Events (AEs) During the Treatment Phase
timeFrame: From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks.
Secondary outcomes:
measure: Change From Baseline in Disease Activity Score in 28 Joints (DAS 28) by Erythrocyte Sedimentation Rate (ESR) at Week 48
timeFrame: Baseline and Week 48.
measure: Percentage of Patients Meeting American College of Rheumatology (ACR) 20% Response Criteria at Week 48
timeFrame: Week 48.
measure: Percentage of Patients Who Meet the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) Definition of Remission at Week 48
timeFrame: Week 48.
measure: Percentage of Patients With European League Against Rheumatism (EULAR) Response (Good Response, Moderate Response, or no Response) at Week 48
timeFrame: Week 48.
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Mesa
country: United States
facility: Arizona Arthritis and Rheumatology Research, PLLC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis and Rheumatology Research, PLLC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis and Rheumatology Research, PLLC
state: Arizona
city: El Cajon
country: United States
facility: TriWest Research Associates, LLC
state: California
city: Lakewood
country: United States
facility: Advanced Medical Research, LLC
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials, Inc.
state: California
city: Boynton Beach
country: United States
facility: Orthopedic Research Institute
state: Florida
city: Jupiter
country: United States
facility: Science and Research Institute, Inc.
state: Florida
city: Miami
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami
country: United States
facility: L&C Professional Medical Research Institute
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Venice
country: United States
facility: Lovelace Scientific Resources, Incorporated
state: Florida
city: Indianapolis
country: United States
facility: Goldpoint Clinical Research, LLC
state: Indiana
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Grand Rapids
country: United States
facility: Arthritis Education and Treatment Center
state: Michigan
city: Lincoln
country: United States
facility: Accurate Clinical Research, Inc.
state: Nebraska
city: Albuquerque
country: United States
facility: Albuquerque Center For Rheumatology
state: New Mexico
city: Dayton
country: United States
facility: STAT Research, Incorporated
state: Ohio
city: Toledo
country: United States
facility: Clinical Research Source, Inc.
state: Ohio
city: Nashville
country: United States
facility: Center for Inflammatory Disease
state: Tennessee
city: Corpus Christi
country: United States
facility: Adriana Pop Moody Clinic PA
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Management LLC
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research, Incorporated
state: Texas
city: Houston
country: United States
facility: Rheumatology Clinic Of Houston, P.A.
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research, Incorporated
state: Texas
city: Lubbock
country: United States
facility: Arthritis & Osteoporosis Associates LLP
state: Texas
city: San Antonio
country: United States
facility: Heartland Research Associates, LLC
state: Texas
city: Danville
country: United States
facility: Danville Orthopedic Clinic, Incorporated
state: Virginia
city: Spokane
country: United States
facility: Arthritis Northwest, PLLC
state: Washington
city: Plovdiv
country: Bulgaria
facility: MHAT "Eurohospital" - Plovdiv, OOD
city: Plovdiv
country: Bulgaria
facility: MHAT "Trimontium", OOD, Plovdiv
city: Plovdiv
country: Bulgaria
facility: MHAT - Kaspela, EOOD
city: Ruse
country: Bulgaria
facility: Medical Center "Teodora", EOOD, Ruse
city: Ruse
country: Bulgaria
facility: MHAT,Fourth Dept. of Therapeutics & Cardiology, Ruse
city: Shumen
country: Bulgaria
facility: MHAT Shumen AD, Shumen
city: Sofia
country: Bulgaria
facility: MMA HAT Sofia, Bulgaria
city: Sofia
country: Bulgaria
facility: UMHAT Sv. Ivan Rilski EAD
city: Veliko Tarnovo
country: Bulgaria
facility: MDHAT 'Dr. Stefan Cherkezov', AD
city: Osorno
country: Chile
facility: Corporacion de Beneficencia Osorno
city: Puerto Varas
country: Chile
facility: Quantum Research Santiago, Puerto Varas
city: Santiago
country: Chile
facility: Centro Medico Prosalud
city: Santiago
country: Chile
facility: BIOMEDICA, Santiago
city: Viña del Mar
country: Chile
facility: CINVEC - Centro de Investigacion Clinica V Reg.,Vina del Mar
city: Pärnu
country: Estonia
facility: Pärnu Hospital, Pärnu
city: Tartu
country: Estonia
facility: Medita Kliinik OÜ, Tartu
city: Bad Doberan
country: Germany
facility: Rheumazentrum Prof. Dr. G. Neeck, Bad Doberan
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klin. Kozpont
city: Veszprem
country: Hungary
facility: Csolnoky Ferenc Korhaz, Veszprem
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
city: Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Bialystok
country: Poland
facility: Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im.dr J. Biziela
city: Elblag
country: Poland
facility: Wojewodzki Szpital Zespolony w Elblagu
city: Gdynia
country: Poland
facility: Medica Pro Familia Spolka Akcyjna, Oddzial w Gdyni
city: Grodzisk Mazowiecki
country: Poland
facility: MCBK Iwona Czajkowska Anna Podrazka- Szczepaniak S.C.
city: Katowice
country: Poland
facility: Medical Centre Pratia Katowice I
city: Krakow
country: Poland
facility: Medical Centre Pratia Krakow
city: Krakow
country: Poland
facility: Specialist Center ALL-MED, Krakow
city: Torun
country: Poland
facility: Niepubliczny ZOZ, "Nasz Lekarz", Lekarzy Rodzinnych z
city: Warszawa
country: Poland
facility: Medical Centre Pratia Warszawa
city: Warszawa
country: Poland
facility: Reumatika, Rheumatology Center, non-public outpatient clinic
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny we Wroclawiu
city: Kemerovo
country: Russian Federation
facility: Kemerovo SMA b/o War Veterans Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Practicheskaya Meditsina Ltd
city: Petrozavodsk
country: Russian Federation
facility: Republic Kareliya Republican Hosp. named after V.A. Baranov
city: Samara
country: Russian Federation
facility: Samara Regional Clinical Hospital n.a MI Kalinin, Samara
city: Stavropol
country: Russian Federation
facility: Stavropol State Medical Academy
city: Yaroslavl
country: Russian Federation
facility: Emergency Clinical Hospital n. a. N. V. Solovyev, Yaroslavl
city: Yaroslavl
country: Russian Federation
facility: SBHI of Yaroslavl Area "Clinical Hospital #3"
city: Belgrade
country: Serbia
facility: Institute of Rheumatology, Belgrade
city: Niska Banja
country: Serbia
facility: Institute for Treatment and Rehabilitation, Niska Banja
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina
city: Sabac
country: Serbia
facility: General Hospital "Dr Laza K. Lazarevic" Sabac, Sabac
city: Barakaldo
country: Spain
facility: Hospital Universitario de Cruces
city: Santiago de Compostela
country: Spain
facility: Hosp. Nuestra Señora de la Esperanza, Santiago de Compostela
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico de Santiago
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Nat. Medical University, Dept. Endocrinology
city: Kharkiv
country: Ukraine
facility: L.T. Malaya Institute of Therapy AMS of Ukraine
city: Kharkiv
country: Ukraine
facility: CI of Healthcare Kharkiv CCH #8, Kharkiv
city: Kyiv
country: Ukraine
facility: SI NSC M.D. Strazhesko Institute Cardiology of NAMSU, Kyiv
city: Kyiv
country: Ukraine
facility: Kjiv City Oleksandrivska Clinical Hospital
city: Kyiv
country: Ukraine
facility: SI D.F.Chebotariov Institute of Gerontology of NAMSU, Kyiv
city: Poltava
country: Ukraine
facility: M.V. Sklifosovskyi Poltava RCH, Poltava
city: Vinnytsia
country: Ukraine
facility: M.I. Pyrogov VRCH, Vinnytsia
city: Vinnytsia
country: Ukraine
facility: MCIC MC LLC Health Clinic, Vinnytsia
city: Zaporizhzhia
country: Ukraine
facility: Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: Cohen SB, Czeloth N, Lee E, Klimiuk PA, Peter N, Jayadeva G. Long-term safety, efficacy, and immunogenicity of adalimumab biosimilar BI 695501 and adalimumab reference product in patients with moderately-to-severely active rheumatoid arthritis: results from a phase 3b extension study (VOLTAIRE-RAext). Expert Opin Biol Ther. 2019 Oct;19(10):1097-1105. doi: 10.1080/14712598.2019.1645114. Epub 2019 Aug 6.