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

NCT ID: NCT02640612

Last Updated: 2018-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 430 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-22
• Study Completion Date: 2017-11-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BI 695501

Group Type: EXPERIMENTAL

BI 695501

Intervention Type: DRUG

Interventions

BI 695501

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Pinnacle Research Group, LLC

Anniston, Alabama, United States

Arizona Arthritis and Rheumatology Research, PLLC

Mesa, Arizona, United States

Arizona Arthritis and Rheumatology Research, PLLC

Phoenix, Arizona, United States

Arizona Arthritis and Rheumatology Research, PLLC

Phoenix, Arizona, United States

TriWest Research Associates, LLC

El Cajon, California, United States

Advanced Medical Research, LLC

Lakewood, California, United States

Inland Rheumatology Clinical Trials, Inc.

Upland, California, United States

Orthopedic Research Institute

Boynton Beach, Florida, United States

Science and Research Institute, Inc.

Jupiter, Florida, United States

San Marcus Research Clinic, Inc.

Miami, Florida, United States

L&C Professional Medical Research Institute

Miami, Florida, United States

Clinical Research of West Florida, Inc.

Tampa, Florida, United States

Lovelace Scientific Resources, Incorporated

Venice, Florida, United States

Goldpoint Clinical Research, LLC

Indianapolis, Indiana, United States

Heartland Research Associates, LLC

Wichita, Kansas, United States

Clinical Pharmacology Study Group

Worcester, Massachusetts, United States

Arthritis Education and Treatment Center

Grand Rapids, Michigan, United States

Accurate Clinical Research, Inc.

Lincoln, Nebraska, United States

Albuquerque Center For Rheumatology

Albuquerque, New Mexico, United States

STAT Research, Incorporated

Dayton, Ohio, United States

Clinical Research Source, Inc.

Toledo, Ohio, United States

Center for Inflammatory Disease

Nashville, Tennessee, United States

Adriana Pop Moody Clinic PA

Corpus Christi, Texas, United States

Accurate Clinical Management LLC

Houston, Texas, United States

Accurate Clinical Research, Incorporated

Houston, Texas, United States

Rheumatology Clinic Of Houston, P.A.

Houston, Texas, United States

Accurate Clinical Research, Incorporated

Houston, Texas, United States

Arthritis & Osteoporosis Associates LLP

Lubbock, Texas, United States

Heartland Research Associates, LLC

San Antonio, Texas, United States

Danville Orthopedic Clinic, Incorporated

Danville, Virginia, United States

Arthritis Northwest, PLLC

Spokane, Washington, United States

MHAT "Eurohospital" - Plovdiv, OOD

Plovdiv, , Bulgaria

MHAT "Trimontium", OOD, Plovdiv

Plovdiv, , Bulgaria

MHAT - Kaspela, EOOD

Plovdiv, , Bulgaria

Medical Center "Teodora", EOOD, Ruse

Rousse, , Bulgaria

MHAT,Fourth Dept. of Therapeutics & Cardiology, Ruse

Rousse, , Bulgaria

MHAT Shumen AD, Shumen

Shumen, , Bulgaria

MMA HAT Sofia, Bulgaria

Sofia, , Bulgaria

UMHAT Sv. Ivan Rilski EAD

Sofia, , Bulgaria

MDHAT 'Dr. Stefan Cherkezov', AD

Veliko Tarnovo, , Bulgaria

Corporacion de Beneficencia Osorno

Osorno, , Chile

Quantum Research Santiago, Puerto Varas

Puerto Varas, , Chile

Centro Medico Prosalud

Santiago, , Chile

BIOMEDICA, Santiago

Santiago, , Chile

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

Viña del Mar, , Chile

Pärnu Hospital, Pärnu

Pärnu, , Estonia

Medita Kliinik OÜ, Tartu

Tartu, , Estonia

Rheumazentrum Prof. Dr. G. Neeck, Bad Doberan

Bad Doberan, , Germany

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klin. Kozpont

Szeged, , Hungary

Csolnoky Ferenc Korhaz, Veszprem

Veszprém, , Hungary

Hospital Tengku Ampuan Afzan

Kuantan, , Malaysia

Hospital Pulau Pinang

Pulau Pinang, , Malaysia

Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk

Bialystok, , Poland

Szpital Uniwersytecki nr 2 im.dr J. Biziela

Bydgoszcz, , Poland

Wojewodzki Szpital Zespolony w Elblagu

Elblag, , Poland

Medica Pro Familia Spolka Akcyjna, Oddzial w Gdyni

Gdynia, , Poland

MCBK Iwona Czajkowska Anna Podrazka- Szczepaniak S.C.

Grodzisk Mazowiecki, , Poland

Medical Centre Pratia Katowice I

Katowice, , Poland

Medical Centre Pratia Krakow

Krakow, , Poland

Specialist Center ALL-MED, Krakow

Krakow, , Poland

Niepubliczny ZOZ, "Nasz Lekarz", Lekarzy Rodzinnych z

Torun, , Poland

Medical Centre Pratia Warszawa

Warsaw, , Poland

Reumatika, Rheumatology Center, non-public outpatient clinic

Warsaw, , Poland

Wojewodzki Szpital Specjalistyczny we Wroclawiu

Wroclaw, , Poland

Kemerovo SMA b/o War Veterans Regional Clinical Hospital

Kemerovo, , Russia

Practicheskaya Meditsina Ltd

Moscow, , Russia

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

Petrozavodsk, , Russia

Samara Regional Clinical Hospital n.a MI Kalinin, Samara

Samara, , Russia

Stavropol State Medical Academy

Stavropol, , Russia

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

Yaroslavl, , Russia

SBHI of Yaroslavl Area "Clinical Hospital #3"

Yaroslavl, , Russia

Institute of Rheumatology, Belgrade

Belgrade, , Serbia

Institute for Treatment and Rehabilitation, Niska Banja

Niška Banja, , Serbia

Clinical Center of Vojvodina

Novi Sad, , Serbia

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

Šabac, , Serbia

Chungnam National University Hospital

Daejeon, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Hospital Universitario de Cruces

Barakaldo, , Spain

Hosp. Nuestra Señora de la Esperanza, Santiago de Compostela

Santiago de Compostela, , Spain

Hospital Clínico de Santiago

Santiago de Compostela, , Spain

Siriraj Hospital

Bangkok, , Thailand

Ivano-Frankivsk Nat. Medical University, Dept. Endocrinology

Ivano-Frankivsk, , Ukraine

L.T. Malaya Institute of Therapy AMS of Ukraine

Kharkiv, , Ukraine

CI of Healthcare Kharkiv CCH #8, Kharkiv

Kharkiv, , Ukraine

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

Kyiv, , Ukraine

Kjiv City Oleksandrivska Clinical Hospital

Kyiv, , Ukraine

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

Kyiv, , Ukraine

M.V. Sklifosovskyi Poltava RCH, Poltava

Poltava, , Ukraine

M.I. Pyrogov VRCH, Vinnytsia

Vinnytsia, , Ukraine

MCIC MC LLC Health Clinic, Vinnytsia

Vinnytsia, , Ukraine

Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia

Zaporizhzhia, , Ukraine

Countries

United States; Bulgaria; Chile; Estonia; Germany; Hungary; Malaysia; Poland; Russia; Serbia; South Korea; Spain; Thailand; Ukraine

References

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.

Reference Type: DERIVED

PMID: 33263165 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32363771 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31387417 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-002634-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1297.3

Identifier Type: -

Identifier Source: org_study_id