A multicenter, double-blind, randomized, active controlled, parallel-group study to evaluate the efficacy, safety, tolerability, and pharmacodynamic profiles of TL011 infusions compared with MabThera® (rituximab) in subjects with severe, active rheumatoid arthritis treated with methotrexate (MTX)
- Conditions
- rheumatoid arthritis10027665
- Registration Number
- NL-OMON37109
- Lead Sponsor
- TEVA Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 20
1. Aged 18-80 years (inclusive) at screening.
2. Rheumatoid arthritis for at least 6 months, as defined by the Revised Criteria ACR 1987 (adult onset RA).
3. Severe, active, seropositive (plasma RF level of at least 20 IU/mL and/or ACPA/anti-CCP positive) disease as defined by the following, revealed in screening tests:
• Active disease defined as presence of at least 8 swollen and 8 tender joints (at the screening visit).
• A serum CRP level of >=15 mg/L (>=1.5 mg/dL) and/or an ESR (Westergren method) of >=28 mm per hour at screening.
4. Inadequate response or intolerance DMARDs other than MTX and/or TNFi therapies (1 or more).
5. Treatment with MTX (10 to 25 mg/week) for at least 12 weeks prior to screening, with at least 4 weeks before screening at a stable dosage that will remain stable throughout the study period
(up to Week 48).
6. Willing and able to provide written informed consent prior to performing study procedures.
7. Women or men of reproductive potential must use (or have his/her partner use) effective contraceptive methods starting from screening and until 12 months following the last infusion (acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner*s vasectomy or double-barrier method [condom or diaphragm with spermicide]).
1. Documented rheumatic autoimmune disease or inflammatory joint disease other than RA (eg, psoriatic arthritis or ankylosing spondylitis).
2. Significant systemic involvement secondary to RA (eg, vasculitis, pulmonary fibrosis, or Felty*s syndrome) or American Rheumatism Association (ARA) functional class IV disease.
3. Hypersensitivity to active ingredients, excipients (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water for injections) and murine proteins.
4. Active uncontrolled infection (viral, bacterial or fungal infection) requiring systemic therapy or clinically significant infection, at screening and/or at Day 1 (baseline), or a history of recurring or
chronic infections or with underlying conditions that may, according to the Investigator*s judgment, further predispose subjects to serious infection.
5. Known immunodeficiency syndrome, including total immunoglobulins (IgG, IgA and IgM) lower than the lower limit of normal (LLN).
6. Positive human immunodeficiency virus (HIV) serology (in case of positive result an additional HIV RNA test should be performed), positive hepatitis B surface antigen or positive
hepatitis C antigen (in case of positive result an additional hepatitis C virus [HCV] RNA test should be performed).
7. History of cancer in the past 5 years prior to screening (except basal-cell carcinoma of the skin that has been excised).
8. Immunization with live viral vaccines less than 4 weeks prior to Day 1 (baseline) and/or planned live viral vaccination during the core study period and/or the anticipated B cell depletion period.
9. Use of oral/intravenous/intramuscular systemic corticosteroids
• Oral corticosteroids at a dose higher than 10 mg prednisone daily (or an equivalent dose of other oral steroids) within the 4 weeks prior to screening and between screening and Day 1
(baseline)
OR
• Oral corticosteroids at a dose equal to or lower than 10 mg prednisone daily (or an equivalent dose of other oral steroids) that were not kept at a stable dose within 4 weeks prior to screening and between screening and Day 1 (baseline).
• Use of intravenous/intramuscular/intra-articular or parenteral glucocorticoids <4 weeks prior to screening.
10. Use of any cytotoxic therapies and immunosuppressants, (except for allowed dosage of MTX) or other DMARDs within the 4 weeks prior to screening or between screening and Day 1
(baseline).
11. Prior use of MabThera (rituximab) and/or participation in a previous clinical trial with the investigational study drug TL011.
12. Use of TNFi and any other biological agent for the treatment of autoimmune diseases less than 8 weeks prior to Day 1 (baseline) or use of etanercept and anakinra less than 4 weeks prior to Day 1.
13. Participation in a previous clinical trial and/or use of an investigational drug within 90 days of screening.
14. Clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation based on the Investigator*s judgment. Conditions may include cardiovascular disease (including severe heart failure of New York Heart Association [NYHA] class IV or severe, uncontrolled cardiac disease) pulmonary, hepatic, renal, or neurological disease as determined by medical history, physical examination, laboratory tests, chest X-ray, or ECG.
15. Likely to be non-compliant or uncooperative during the study in
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary efficacy endpoint:<br /><br>Proportion of subjects (%) who meet the ACR20 criteria defined as at least a<br /><br>20% improvement from baseline values in swollen joint count,<br /><br>tender joint count, and 3 of the following 5 (core set items) disease activity<br /><br>measures at Week 24:<br /><br>• Subject*s assessment of pain using a visual analog scale (VAS).<br /><br>• Subject*s global assessment of disease activity (VAS).<br /><br>• Physician*s global assessment of disease activity (VAS).<br /><br>• Health Assessment Questionnaire (HAQ).<br /><br>• Acute phase reactant value (CRP will be used for analysis. ESR can be used if<br /><br>CRP data is missing).</p><br>
- Secondary Outcome Measures
Name Time Method