AzTrials
AzTrials

Arthritis, RheumatoidPhase 3NCT02640612

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

A Phase 3 study testing BI 695501 in people with Arthritis, Rheumatoid, run by Boehringer Ingelheim at 91 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. 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 695501
Could I receive a placebo?
No, everyone receives an active treatment
How many people
430 participants
Where
91 sitesin 14 countries
Study dates
22 Jan 2016to 1 Nov 2017
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

  • 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).

Who cannot join

  • 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
Show all 26Show fewer
  • 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

Trial locations and contacts

91 sites in 14 countries.

91 sites in 14 countries

United States31 sites

  • Albuquerque Center For Rheumatology

    Albuquerque, New Mexico, 87102

  • Pinnacle Research Group, LLC

    Anniston, Alabama, 36207

  • Orthopedic Research Institute

    Boynton Beach, Florida, 33437

  • Adriana Pop Moody Clinic PA

    Corpus Christi, Texas, 78404

  • Danville Orthopedic Clinic, Incorporated

    Danville, Virginia, 24541

  • STAT Research, Incorporated

    Dayton, Ohio, 45417

  • TriWest Research Associates, LLC

    El Cajon, California, 92020-4124

  • Arthritis Education and Treatment Center

    Grand Rapids, Michigan, 49546

  • Accurate Clinical Management LLC

    Houston, Texas, 77004

  • Accurate Clinical Research, Incorporated

    Houston, Texas, 77034

  • Rheumatology Clinic Of Houston, P.A.

    Houston, Texas, 77065

  • Accurate Clinical Research, Incorporated

    Houston, Texas

  • Goldpoint Clinical Research, LLC

    Indianapolis, Indiana, 46260

  • Science and Research Institute, Inc.

    Jupiter, Florida, 33458

  • Advanced Medical Research, LLC

    Lakewood, California, 90712

  • Accurate Clinical Research, Inc.

    Lincoln, Nebraska, 68516

  • Arthritis & Osteoporosis Associates LLP

    Lubbock, Texas, 79424

  • Arizona Arthritis and Rheumatology Research, PLLC

    Mesa, Arizona, 85202

  • San Marcus Research Clinic, Inc.

    Miami, Florida, 33015

  • L&C Professional Medical Research Institute

    Miami, Florida, 33144

  • Center for Inflammatory Disease

    Nashville, Tennessee, 37205

  • Arizona Arthritis and Rheumatology Research, PLLC

    Phoenix, Arizona, 85032

  • Arizona Arthritis and Rheumatology Research, PLLC

    Phoenix, Arizona, 85037

  • Heartland Research Associates, LLC

    San Antonio, Texas, 78229

  • Arthritis Northwest, PLLC

    Spokane, Washington, 99204

  • Clinical Research of West Florida, Inc.

    Tampa, Florida, 33603

  • Clinical Research Source, Inc.

    Toledo, Ohio, 43606

  • Inland Rheumatology Clinical Trials, Inc.

    Upland, California, 91786

  • Lovelace Scientific Resources, Incorporated

    Venice, Florida, 34292

  • Heartland Research Associates, LLC

    Wichita, Kansas, 67207

  • Clinical Pharmacology Study Group

    Worcester, Massachusetts, 01605

Other trials in United States

Poland12 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

  • Medica Pro Familia Spolka Akcyjna, Oddzial w Gdyni

    Gdynia, 81-338

  • MCBK Iwona Czajkowska Anna Podrazka- Szczepaniak S.C.

    Grodzisk Mazowiecki, 05-825

  • Medical Centre Pratia Katowice I

    Katowice, 40-954

  • Medical Centre Pratia Krakow

    Krakow, 30-002

  • Specialist Center ALL-MED, Krakow

    Krakow, 31-023

  • Niepubliczny ZOZ, "Nasz Lekarz", Lekarzy Rodzinnych z

    Torun, 87-100

  • Medical Centre Pratia Warszawa

    Warsaw, 01-868

  • Reumatika, Rheumatology Center, non-public outpatient clinic

    Warsaw, 02-691

  • Wojewodzki Szpital Specjalistyczny we Wroclawiu

    Wroclaw, 51-124

Other trials in Poland

Ukraine10 sites

  • Ivano-Frankivsk Nat. Medical University, Dept. Endocrinology

    Ivano-Frankivsk, 76008

  • L.T. Malaya Institute of Therapy AMS of Ukraine

    Kharkiv, 61039

  • CI of Healthcare Kharkiv CCH #8, Kharkiv

    Kharkiv, 61176

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

    Kyiv, 03680

  • Kjiv City Oleksandrivska Clinical Hospital

    Kyiv, 1601

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

    Kyiv, 4114

  • M.V. Sklifosovskyi Poltava RCH, Poltava

    Poltava, 36011

  • M.I. Pyrogov VRCH, Vinnytsia

    Vinnytsia, 21018

  • MCIC MC LLC Health Clinic, Vinnytsia

    Vinnytsia, 21029

  • Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia

    Zaporizhzhya, 69600

Other trials in Ukraine

Bulgaria9 sites

  • MHAT "Eurohospital" - Plovdiv, OOD

    Plovdiv, 4000

  • MHAT "Trimontium", OOD, Plovdiv

    Plovdiv, 4000

  • MHAT - Kaspela, EOOD

    Plovdiv, 4002

  • Medical Center "Teodora", EOOD, Ruse

    Rousse, 7000

  • MHAT,Fourth Dept. of Therapeutics & Cardiology, Ruse

    Rousse, 7002

  • MHAT Shumen AD, Shumen

    Shumen, 9700

  • MMA HAT Sofia, Bulgaria

    Sofia, 1606

  • UMHAT Sv. Ivan Rilski EAD

    Sofia, 1612

  • MDHAT 'Dr. Stefan Cherkezov', AD

    Veliko Tarnovo, 5000

Other trials in Bulgaria

Russia7 sites

  • Kemerovo SMA b/o War Veterans Regional Clinical Hospital

    Kemerovo, 650000

  • Practicheskaya Meditsina Ltd

    Moscow, 115404

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

    Petrozavodsk, 185019

  • Samara Regional Clinical Hospital n.a MI Kalinin, Samara

    Samara, 443095

  • Stavropol State Medical Academy

    Stavropol, 355017

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

    Yaroslavl, 150003

  • SBHI of Yaroslavl Area "Clinical Hospital #3"

    Yaroslavl, 150051

Other trials in Russia

Chile5 sites

  • Corporacion de Beneficencia Osorno

    Osorno, 5290000

  • Quantum Research Santiago, Puerto Varas

    Puerto Varas, 5550170

  • Centro Medico Prosalud

    Santiago, 7500000

  • BIOMEDICA, Santiago

    Santiago, 7500710

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

    Viña del Mar, 2570017

Other trials in Chile

Serbia4 sites

  • Institute of Rheumatology, Belgrade

    Belgrade, 11000

  • Institute for Treatment and Rehabilitation, Niska Banja

    Niška Banja, 18205

  • Clinical Center of Vojvodina

    Novi Sad, 21000

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

    Šabac, 15000

Other trials in Serbia

Spain3 sites

  • Hospital Universitario de Cruces

    Barakaldo, 48903

  • Hosp. Nuestra Señora de la Esperanza, Santiago de Compostela

    Santiago de Compostela, 15705

  • Hospital Clínico de Santiago

    Santiago de Compostela, 15706

Other trials in Spain

Estonia2 sites

  • Pärnu Hospital, Pärnu

    Pärnu, 80010

  • Medita Kliinik OÜ, Tartu

    Tartu, 50107

Other trials in Estonia

Hungary2 sites

  • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klin. Kozpont

    Szeged, 6725

  • Csolnoky Ferenc Korhaz, Veszprem

    Veszprém, 8200

Other trials in Hungary

Malaysia2 sites

  • Hospital Tengku Ampuan Afzan

    Kuantan, 25100

  • Hospital Pulau Pinang

    Pulau Pinang, 10990

Other trials in Malaysia

South Korea2 sites

  • Chungnam National University Hospital

    Daejeon, 35015

  • Seoul National University Hospital

    Seoul, 03080

Other trials in South Korea

Germany1 site

  • Rheumazentrum Prof. Dr. G. Neeck, Bad Doberan

    Bad Doberan, 18209

Other trials in Germany

Thailand1 site

  • Siriraj Hospital

    Bangkok, 10700

Other trials in Thailand

About this study

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

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.
Being tested
BI 695501
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 695501Drug

Study groups in NCT02640612
Study groupRoleWhat they receive
BI 695501ExperimentalNot described
Receives: Drug: BI 695501

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

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

    The DAS28 (ESR) score was derived using the following formulae: DAS28 (ESR) = 0.56*√(TJC28) + 0.28*√(SJC28) + 0.014*(GH) + 0.7*ln(ESR) Where: • TJC28 = 28 joint count for tenderness • SJC28 = 28 joint count for swelling • GH = General Health component of the DAS (patient's global assessment of disease activity) • Ln (ESR) = natural logarithm of ESR. Last observation carried forward (LOCF) is the method used for handling missing components post baseline. Baseline for this trial was taken from the baseline of 1297.2. Improvement in DAS28 was also categorized using the European League Against Rheumatism (EULAR) response criteria. The DAS28 provides a number on a scale from 0 to 10 where higher values mean a higher disease activity. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.

    Measured: Baseline and Week 48.

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

    The proportion of patients meeting the ACR20 response criteria was assessed. A patient had an ACR20 response if all of the following occurred: 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 three of the following assessments: Patient's assessment of pain, Patient's global assessment of disease activity (equivalent to the General Health component of the Disease Activity Score ([DAS]), Physician's global assessment of disease activity, Patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI) Acute phase reactant (C-reactive protein [CRP]).

    Measured: Week 48.

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

    The ACR/EULAR remission criteria were based on a Boolean definition. At any time point, the patient must have satisfied all of the following:

    • Tender joint count (TJC) ≤ 1
    • Swollen joint count (SJC) ≤ 1
    • C-reactive protein (CRP) ≤ 1 mg/dL
    • Patient global assessment of disease activity ≤ 10 (on a 0 to 100 scale) For TJC and SJC, use of a 28-joint count may have missed actively involved joints, particularly in the feet and ankles. It was preferable to include the feet and ankles when evaluating remission.

    Measured: Week 48.

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

    Percentage of patients with European League Against Rheumatism (EULAR) response (good response, moderate response, or no response) were calculated at Week 48 for assessment of this outcome measure.

    No response: If improvement in DAS28 (ESR) at w48 <=0.6, or if DAS28(ESR) at w48 >5.1 and improvement is in range >0.6 to <1.2.

    Moderate response: If DAS28(ESR) at w48 <=5.1 and improvement is in range >0.6 to <1.2, or, DAS28(ESR) at w48 >3.2 and improvement is in range >=1.2.

    Good response: If DAS28(ESR) at w48 <=3.2 and improvement >=1.2.

    Measured: Week 48.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Dec 2015 (estimated)
  2. Study start22 Jan 2016
  3. Primary completion1 Nov 2017
  4. Study completion1 Nov 2017

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
430 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02640612
Sponsor's protocol ID
1297.3
Other IDs
2015-002634-41, 2015
Status last verified
Dec 2018
First submitted
18 Dec 2015
Last updated
5 Dec 2018

Publications

  • 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.

    PubMed 33263165

  • 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.

    PubMed 32363771

  • 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.

    PubMed 31387417

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BI 695501 in people with Arthritis, Rheumatoid, run by Boehringer Ingelheim at 91 sites in 14 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 4 inclusion and 26 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: finished, as of the sponsor's last update on 5 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 91 sites in United States, Poland, Ukraine, Bulgaria, Russia and 9 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 5 Dec 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?

Percentage of Patients With Drug-related Adverse Events (AEs) During the Treatment Phase (time frame: From the first drug administration until 10 weeks after the last drug administration, up to 58 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02640612, which also lists 3 linked publications.

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 5 Dec 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in