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

Arthritis, Rheumatoid Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02640612
• Other study ID #: 1297.3
• Secondary ID: 2015-002634-41
• Status: Completed
• Phase: Phase 3
• Start date: January 22, 2016
• Est. completion date: November 1, 2017

Study information

• Verified date: December 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 430
• Est. completion date: November 1, 2017
• Est. primary completion date: November 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• BI 695501

Locations

Country	Name	City	State
Bulgaria	MHAT "Eurohospital" - Plovdiv, OOD	Plovdiv
Bulgaria	MHAT "Trimontium", OOD, Plovdiv	Plovdiv
Bulgaria	MHAT - Kaspela, EOOD	Plovdiv
Bulgaria	Medical Center "Teodora", EOOD, Ruse	Ruse
Bulgaria	MHAT,Fourth Dept. of Therapeutics & Cardiology, Ruse	Ruse
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
Chile	Corporacion de Beneficencia Osorno	Osorno
Chile	Quantum Research Santiago, Puerto Varas	Puerto Varas
Chile	BIOMEDICA, Santiago	Santiago
Chile	Centro Medico Prosalud	Santiago
Chile	CINVEC - Centro de Investigacion Clinica V Reg.,Vina del Mar	Viña del Mar
Estonia	Pärnu Hospital, Pärnu	Pärnu
Estonia	Medita Kliinik OÜ, Tartu	Tartu
Germany	Rheumazentrum Prof. Dr. G. Neeck, Bad Doberan	Bad Doberan
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klin. Kozpont	Szeged
Hungary	Csolnoky Ferenc Korhaz, Veszprem	Veszprem
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Seoul National University Hospital	Seoul
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan
Malaysia	Hospital Pulau Pinang	Pulau Pinang
Poland	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	Warszawa
Poland	Reumatika, Rheumatology Center, non-public outpatient clinic	Warszawa
Poland	Wojewodzki Szpital Specjalistyczny we Wroclawiu	Wroclaw
Russian Federation	Kemerovo SMA b/o War Veterans Regional Clinical Hospital	Kemerovo
Russian Federation	Practicheskaya Meditsina Ltd	Moscow
Russian Federation	Republic Kareliya Republican Hosp. named after V.A. Baranov	Petrozavodsk
Russian Federation	Samara Regional Clinical Hospital n.a MI Kalinin, Samara	Samara
Russian Federation	Stavropol State Medical Academy	Stavropol
Russian Federation	Emergency Clinical Hospital n. a. N. V. Solovyev, Yaroslavl	Yaroslavl
Russian Federation	SBHI of Yaroslavl Area "Clinical Hospital #3"	Yaroslavl
Serbia	Institute of Rheumatology, Belgrade	Belgrade
Serbia	Institute for Treatment and Rehabilitation, Niska Banja	Niska Banja
Serbia	Clinical Center of Vojvodina	Novi Sad
Serbia	General Hospital "Dr Laza K. Lazarevic" Sabac, Sabac	Sabac
Spain	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
Thailand	Siriraj Hospital	Bangkok
Ukraine	Ivano-Frankivsk Nat. Medical University, Dept. Endocrinology	Ivano-Frankivsk
Ukraine	CI of Healthcare Kharkiv CCH #8, Kharkiv	Kharkiv
Ukraine	L.T. Malaya Institute of Therapy AMS of Ukraine	Kharkiv
Ukraine	Kjiv City Oleksandrivska Clinical Hospital	Kyiv
Ukraine	SI D.F.Chebotariov Institute of Gerontology of NAMSU, Kyiv	Kyiv
Ukraine	SI NSC M.D. Strazhesko Institute Cardiology 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
United States	Albuquerque Center For Rheumatology	Albuquerque	New Mexico
United States	Pinnacle Research Group, LLC	Anniston	Alabama
United States	Orthopedic Research Institute	Boynton Beach	Florida
United States	Adriana Pop Moody Clinic PA	Corpus Christi	Texas
United States	Danville Orthopedic Clinic, Incorporated	Danville	Virginia
United States	STAT Research, Incorporated	Dayton	Ohio
United States	TriWest Research Associates, LLC	El Cajon	California
United States	Arthritis Education and Treatment Center	Grand Rapids	Michigan
United States	Accurate Clinical Management LLC	Houston	Texas
United States	Accurate Clinical Research, Incorporated	Houston	Texas
United States	Accurate Clinical Research, Incorporated	Houston	Texas
United States	Rheumatology Clinic Of Houston, P.A.	Houston	Texas
United States	Goldpoint Clinical Research, LLC	Indianapolis	Indiana
United States	Science and Research Institute, Inc.	Jupiter	Florida
United States	Advanced Medical Research, LLC	Lakewood	California
United States	Accurate Clinical Research, Inc.	Lincoln	Nebraska
United States	Arthritis & Osteoporosis Associates LLP	Lubbock	Texas
United States	Arizona Arthritis and Rheumatology Research, PLLC	Mesa	Arizona
United States	L&C Professional Medical Research Institute	Miami	Florida
United States	San Marcus Research Clinic, Inc.	Miami	Florida
United States	Center for Inflammatory Disease	Nashville	Tennessee
United States	Arizona Arthritis and Rheumatology Research, PLLC	Phoenix	Arizona
United States	Arizona Arthritis and Rheumatology Research, PLLC	Phoenix	Arizona
United States	Heartland Research Associates, LLC	San Antonio	Texas
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	Clinical Research Source, Inc.	Toledo	Ohio
United States	Inland Rheumatology Clinical Trials, Inc.	Upland	California
United States	Lovelace Scientific Resources, Incorporated	Venice	Florida
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Bulgaria,  Chile,  Estonia,  Germany,  Hungary,  Korea, Republic of,  Malaysia,  Poland,  Russian Federation,  Serbia,  Spain,  Thailand,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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*v(TJC28) + 0.28*v(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.	Baseline and Week 48.
Secondary	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]).	Week 48.
Secondary	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.	Week 48.
Secondary	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.	Week 48.

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