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

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.

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