Long-term Assessment of Safety and Efficacy of BI 695501 in Patients With Rheumatoid Arthritis

NCT02640612 | Completed Phase 3 Results

• 2 other identifiers: 1297.32015-002634-41
• Study Type: interventional
• Target: 430
• Locations: 13 countries
• Sites: 89

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.

Conditions

Arthritis, Rheumatoid

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With 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.

  From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks.

Secondary Outcomes (4)

• Change From Baseline in Disease Activity Score in 28 Joints (DAS 28) by Erythrocyte Sedimentation Rate (ESR) at Week 48

  Baseline and Week 48.

• Percentage of Patients Meeting American College of Rheumatology (ACR) 20% Response Criteria at Week 48

  Week 48.

• Percentage of Patients Who Meet the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) Definition of Remission at Week 48

  Week 48.

• Percentage of Patients With European League Against Rheumatism (EULAR) Response (Good Response, Moderate Response, or no Response) at Week 48

  Week 48.

Study Arms (1)

BI 695501

EXPERIMENTAL

Drug: BI 695501

Interventions

BI 695501 DRUG

BI 695501

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (91)

Pinnacle Research Group, LLC

Anniston, Alabama, 36207, United States

Location

Arizona Arthritis and Rheumatology Research, PLLC

Mesa, Arizona, 85202, United States

Location

Arizona Arthritis and Rheumatology Research, PLLC

Phoenix, Arizona, 85032, United States

Location

Arizona Arthritis and Rheumatology Research, PLLC

Phoenix, Arizona, 85037, United States

Location

TriWest Research Associates, LLC

El Cajon, California, 92020-4124, United States

Location

Advanced Medical Research, LLC

Lakewood, California, 90712, United States

Location

Inland Rheumatology Clinical Trials, Inc.

Upland, California, 91786, United States

Location

Orthopedic Research Institute

Boynton Beach, Florida, 33437, United States

Location

Science and Research Institute, Inc.

Jupiter, Florida, 33458, United States

Location

San Marcus Research Clinic, Inc.

Miami, Florida, 33015, United States

Location

L&C Professional Medical Research Institute

Miami, Florida, 33144, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33603, United States

Location

Lovelace Scientific Resources, Incorporated

Venice, Florida, 34292, United States

Location

Goldpoint Clinical Research, LLC

Indianapolis, Indiana, 46260, United States

Location

Heartland Research Associates, LLC

Wichita, Kansas, 67207, United States

Location

Clinical Pharmacology Study Group

Worcester, Massachusetts, 01605, United States

Location

Arthritis Education and Treatment Center

Grand Rapids, Michigan, 49546, United States

Location

Accurate Clinical Research, Inc.

Lincoln, Nebraska, 68516, United States

Location

Albuquerque Center For Rheumatology

Albuquerque, New Mexico, 87102, United States

Location

STAT Research, Incorporated

Dayton, Ohio, 45417, United States

Location

Clinical Research Source, Inc.

Toledo, Ohio, 43606, United States

Location

Center for Inflammatory Disease

Nashville, Tennessee, 37205, United States

Location

Adriana Pop Moody Clinic PA

Corpus Christi, Texas, 78404, United States

Location

Accurate Clinical Management LLC

Houston, Texas, 77004, United States

Location

Accurate Clinical Research, Incorporated

Houston, Texas, 77034, United States

Location

Rheumatology Clinic Of Houston, P.A.

Houston, Texas, 77065, United States

Location

Accurate Clinical Research, Incorporated

Houston, Texas, United States

Location

Arthritis & Osteoporosis Associates LLP

Lubbock, Texas, 79424, United States

Location

Heartland Research Associates, LLC

San Antonio, Texas, 78229, United States

Location

Danville Orthopedic Clinic, Incorporated

Danville, Virginia, 24541, United States

Location

Arthritis Northwest, PLLC

Spokane, Washington, 99204, United States

Location

MHAT "Eurohospital" - Plovdiv, OOD

Plovdiv, 4000, Bulgaria

Location

MHAT "Trimontium", OOD, Plovdiv

Plovdiv, 4000, Bulgaria

Location

MHAT - Kaspela, EOOD

Plovdiv, 4002, Bulgaria

Location

Medical Center "Teodora", EOOD, Ruse

Rousse, 7000, Bulgaria

Location

MHAT,Fourth Dept. of Therapeutics & Cardiology, Ruse

Rousse, 7002, Bulgaria

Location

MHAT Shumen AD, Shumen

Shumen, 9700, Bulgaria

Location

MMA HAT Sofia, Bulgaria

Sofia, 1606, Bulgaria

Location

UMHAT Sv. Ivan Rilski EAD

Sofia, 1612, Bulgaria

Location

MDHAT 'Dr. Stefan Cherkezov', AD

Veliko Tarnovo, 5000, Bulgaria

Location

Corporacion de Beneficencia Osorno

Osorno, 5290000, Chile

Location

Quantum Research Santiago, Puerto Varas

Puerto Varas, 5550170, Chile

Location

Centro Medico Prosalud

Santiago, 7500000, Chile

Location

BIOMEDICA, Santiago

Santiago, 7500710, Chile

Location

CINVEC - Centro de Investigacion Clinica V Reg.,Vina del Mar

Viña del Mar, 2570017, Chile

Location

Pärnu Hospital, Pärnu

Pärnu, 80010, Estonia

Location

Medita Kliinik OÜ, Tartu

Tartu, 50107, Estonia

Location

Rheumazentrum Prof. Dr. G. Neeck, Bad Doberan

Bad Doberan, 18209, Germany

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klin. Kozpont

Szeged, 6725, Hungary

Location

Csolnoky Ferenc Korhaz, Veszprem

Veszprém, 8200, Hungary

Location

Hospital Tengku Ampuan Afzan

Kuantan, 25100, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, 10990, Malaysia

Location

Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk

Bialystok, 15-099, Poland

Location

Szpital Uniwersytecki nr 2 im.dr J. Biziela

Bydgoszcz, 85-168, Poland

Location

Wojewodzki Szpital Zespolony w Elblagu

Elblag, 82-300, Poland

Location

Medica Pro Familia Spolka Akcyjna, Oddzial w Gdyni

Gdynia, 81-338, Poland

Location

MCBK Iwona Czajkowska Anna Podrazka- Szczepaniak S.C.

Grodzisk Mazowiecki, 05-825, Poland

Location

Medical Centre Pratia Katowice I

Katowice, 40-954, Poland

Location

Medical Centre Pratia Krakow

Krakow, 30-002, Poland

Location

Specialist Center ALL-MED, Krakow

Krakow, 31-023, Poland

Location

Niepubliczny ZOZ, "Nasz Lekarz", Lekarzy Rodzinnych z

Torun, 87-100, Poland

Location

Medical Centre Pratia Warszawa

Warsaw, 01-868, Poland

Location

Reumatika, Rheumatology Center, non-public outpatient clinic

Warsaw, 02-691, Poland

Location

Wojewodzki Szpital Specjalistyczny we Wroclawiu

Wroclaw, 51-124, Poland

Location

Kemerovo SMA b/o War Veterans Regional Clinical Hospital

Kemerovo, 650000, Russia

Location

Practicheskaya Meditsina Ltd

Moscow, 115404, Russia

Location

Republic Kareliya Republican Hosp. named after V.A. Baranov

Petrozavodsk, 185019, Russia

Location

Samara Regional Clinical Hospital n.a MI Kalinin, Samara

Samara, 443095, Russia

Location

Stavropol State Medical Academy

Stavropol, 355017, Russia

Location

Emergency Clinical Hospital n. a. N. V. Solovyev, Yaroslavl

Yaroslavl, 150003, Russia

Location

SBHI of Yaroslavl Area "Clinical Hospital #3"

Yaroslavl, 150051, Russia

Location

Institute of Rheumatology, Belgrade

Belgrade, 11000, Serbia

Location

Institute for Treatment and Rehabilitation, Niska Banja

Niška Banja, 18205, Serbia

Location

Clinical Center of Vojvodina

Novi Sad, 21000, Serbia

Location

General Hospital "Dr Laza K. Lazarevic" Sabac, Sabac

Šabac, 15000, Serbia

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Universitario de Cruces

Barakaldo, 48903, Spain

Location

Hosp. Nuestra Señora de la Esperanza, Santiago de Compostela

Santiago de Compostela, 15705, Spain

Location

Hospital Clínico de Santiago

Santiago de Compostela, 15706, Spain

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Ivano-Frankivsk Nat. Medical University, Dept. Endocrinology

Ivano-Frankivsk, 76008, Ukraine

Location

L.T. Malaya Institute of Therapy AMS of Ukraine

Kharkiv, 61039, Ukraine

Location

CI of Healthcare Kharkiv CCH #8, Kharkiv

Kharkiv, 61176, Ukraine

Location

SI NSC M.D. Strazhesko Institute Cardiology of NAMSU, Kyiv

Kyiv, 03680, Ukraine

Location

Kjiv City Oleksandrivska Clinical Hospital

Kyiv, 1601, Ukraine

Location

SI D.F.Chebotariov Institute of Gerontology of NAMSU, Kyiv

Kyiv, 4114, Ukraine

Location

M.V. Sklifosovskyi Poltava RCH, Poltava

Poltava, 36011, Ukraine

Location

M.I. Pyrogov VRCH, Vinnytsia

Vinnytsia, 21018, Ukraine

Location

MCIC MC LLC Health Clinic, Vinnytsia

Vinnytsia, 21029, Ukraine

Location

Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia

Zaporizhzhia, 69600, Ukraine

Location

Related Publications (3)

• 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.

  PMID: 33263165 DERIVED

• 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.

  PMID: 32363771 DERIVED

• 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.

  PMID: 31387417 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

BI 695501

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2015
• First Posted: December 29, 2015
• Study Start: January 22, 2016
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: December 5, 2018
• Results First Posted: December 5, 2018

Record last verified: 2018-12

Locations

PL (12); KR (2); CL (5); MY (2); DE (1); ES (3); US (31); SE (4); UA (10); RU (7); TH (1); HU (2); BU (9)