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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02640612
Recruitment Status : Completed
First Posted : December 29, 2015
Results First Posted : December 5, 2018
Last Update Posted : December 5, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE December 18, 2015
First Posted Date  ICMJE December 29, 2015
Results First Submitted Date  ICMJE October 22, 2018
Results First Posted Date  ICMJE December 5, 2018
Last Update Posted Date December 5, 2018
Actual Study Start Date  ICMJE January 22, 2016
Actual Primary Completion Date November 1, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 3, 2018)
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. ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 23, 2015)
Proportion of patients with drug-related Adverse Events (AEs) during the treatment phase [ Time Frame: 48 weeks ]
Change History Complete list of historical versions of study NCT02640612 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2018)
  • Change From Baseline in Disease Activity Score in 28 Joints (DAS 28) by Erythrocyte Sedimentation Rate (ESR) at Week 48 [ Time Frame: Baseline and 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.
  • Percentage of Patients Meeting American College of Rheumatology (ACR) 20% Response Criteria at Week 48 [ Time Frame: 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]).
  • Percentage of Patients Who Meet the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) Definition of Remission at Week 48 [ Time Frame: 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.
  • Percentage of Patients With European League Against Rheumatism (EULAR) Response (Good Response, Moderate Response, or no Response) at Week 48 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 23, 2015)
  • Change From Baseline in Disease Activity Score in 28 Joints (DAS 28) by Erythrocyte Sedimentation Rate (ESR) at Week 48 [ Time Frame: 48 weeks ]
  • Proportion of patients meeting American College of Rheumatology (ACR) 20% response criteria at Week 48 [ Time Frame: 48 weeks ]
  • Proportion of patients who meet the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) definition of remission at Week 48 [ Time Frame: 48 weeks ]
  • Proportion of patients with European League Against Rheumatism (EULAR) response (good response, moderate response, or no response) at Week 48 [ Time Frame: 48 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Long-term Assessment of Safety and Efficacy of BI 695501 in Patients With Rheumatoid Arthritis
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Arthritis, Rheumatoid
Intervention  ICMJE Drug: BI 695501
Study Arms  ICMJE Experimental: BI 695501
Intervention: Drug: BI 695501
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 15, 2017)
430
Original Estimated Enrollment  ICMJE
 (submitted: December 23, 2015)
400
Actual Study Completion Date  ICMJE November 1, 2017
Actual Primary Completion Date November 1, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Chile,   Estonia,   Germany,   Hungary,   Korea, Republic of,   Malaysia,   Poland,   Russian Federation,   Serbia,   Spain,   Thailand,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02640612
Other Study ID Numbers  ICMJE 1297.3
2015-002634-41 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP