This is a Phase 3 Study to Compare the Pharmacokinetics, Efficacy and Safety between CT-P10, Rituxan and MabThera in Patients with Rheumatoid Arthritis
- Conditions
- Rheumatoid ArthritisMedDRA version: 18.0Level: HLTClassification code 10039075Term: Rheumatoid arthritis and associated conditionsSystem Organ Class: 100000004870Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2013-004555-21-HU
- Lead Sponsor
- CELLTRION, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 361
Each patient must meet all of the following criteria to be enrolled in this study:
1. Patient is male or female between 18 and 75 years old, inclusive.
2. Patient has a diagnosis of RA according to the revised 1987 ACR classification criteria (Arnett et al 1988) for at least 6 months prior to randomization.
3. Patient has active disease as defined by the presence of 6 or more swollen joints (of 66 assessed) and 6 or more tender joints (of 68 assessed), and serum CRP =1.5 mg/dL (=15 mg/L) or an ESR =28 mm/hour.
4. Patient has experienced an inadequate response to previous or current treatment with the anti-TNF agents infliximab (=3 mg/kg; at least 3 infusions for at least 3 months), golimumab (50 mg once a month for at least 12 to 14 weeks or 2 mg/kg IV infusion for at least 3 months), adalimumab (40 mg every other week for at least 3 months), or etanercept (25 mg twice weekly or 50 mg once weekly for at least 3 months), or was intolerant to at least 1 administration of these agents. Patients who discontinued etanercept for at least 4 weeks, infliximab or adalimumab for at least 8 weeks, or golimumab for at least 10 weeks prior to randomization are permitted to enter the study.
Patients who received any other anti-TNF agents not in this list can be enrolled if the patient discontinued the treatment at least 4 weeks or 5 half-lives prior to randomization, whichever is longer.
5. Patient has a proper discontinuation period after treatment with interleukin-1 receptor (IL-1R) antagonist, interleukin-6 receptor (IL-6R) antibody, or abatacept. Patients who discontinued IL-1R antagonist for at least 4 weeks, abatacept for at least 8 weeks, or IL-6R antibody for at least 17 weeks prior to randomization are permitted to enter the study.
Patients who had any other biological drugs not in this list can be enrolled if the patient discontinued the treatment at least 4 weeks or 5 half-lives prior to randomization, whichever is longer.
6. Patient has received MTX treatment (7.5 to 25 mg/week orally or parenterally) for at least the past 12 weeks, with the last 4 weeks at a stable dose before Screening.
7. Patient has the following hematology laboratory test results at Screening:
• Hemoglobin =8.0 g/dL
• White blood cell count =3.5 × 10 3 cells/µL (SI [Système International d'Unités] units: =3.5 × 10 9 cells/L)
• Neutrophil count =1.5 × 10 3 cells/µL (SI units: =1.5 × 10 9 cells/L)
• Platelet count =75× 10 3 cells/µL (SI units: =75 × 10 9 cells/L)
8. Patient has adequate renal and hepatic function at Screening as defined by the following clinical chemistry results:
• Serum creatinine <1.5 × upper limit of normal (ULN) or an estimated creatinine
clearance level >50 mL/min (by Cockcroft-Gault formula)
• Serum alanine aminotransferase <2.5 × ULN
• Serum aspartate aminotransferase <2.5 × ULN
• Serum total bilirubin <2 × ULN
9. Patient has the ability to comprehend the full nature and purpose of the study, including possible risks and side effects, to cooperate with the investigator, to understand verbal and/or written instructions, and to comply with the requirements of the entire study.
10. Patient (or legal guardian, if applicable) has been informed of the full nature and purpose of the study, including possible risks and side effects, and given ample time and opportunity to read and understand this information, and provide signed and dated written informed consent before inclusion in the study.
11. For both male and female patients
Patients meeting any of the following criteria will be excluded from the study:
1. Patient has taken more than 2 biologic agents.
2. Patient has previously been administered Rituximab or participated in a Rituximab biosimilar study.
3. Patient has allergies or hypersensitivity to murine, chimeric, human, or humanized proteins.
4. Patient has current or past history of chronic infection with hepatitis B, hepatitis C, or infection with human immunodeficiency virus (HIV)-1 or -2 or who has a positive result to the screening test for these infections.
5. Patient has an infection requiring oral antibiotics 2 weeks before randomization,
parenteral injection of antibiotics 4 weeks before randomization, other serious infection 6 months before randomization, a history of recurrent herpes zoster or other chronic or recurrent infection 6 weeks before randomization.
6. Patient has a past or current diagnosis of tuberculosis (TB), recent exposure to person with active TB, examination findings indicating the presence of TB, defined as a positive result for interferon-? release assay, or other severe or chronic infection (such as sepsis, abscess or opportunistic infection, or invasive fungal infection such as histoplasmosis). A patient who has a past diagnosis with sufficient documentation of prophylaxis or complete resolution following treatment can be enrolled.
7. Patient is receiving any of the following medications or therapies:
• Previous treatment within 6 months of IV gamma globulin or the Prosorba Column
• Any surgical procedure, including bone or joint surgery or synovectomy (including
joint fusion or replacement) within 12 weeks prior to randomization or planned within 6 months after randomization
• Intra-articular corticosteroids within 8 weeks prior to randomization. Patients are permitted to receive either oral or parenteral glucocorticoids (=10 mg daily of
prednisone/prednisolone or equivalent), and nonsteroidal anti-inflammatory drug, if they have received a stable dose for at least 4 weeks prior to randomization. In
addition, patients are permitted to receive low potency topical, otic, and ophthalmic glucocorticoid preparations provided the preparations are administered per the instructions on the product label.
• Disease-modifying antirheumatic drugs, other than MTX, including
hydroxychloroquine, chloroquine, or sulfasalazine, within 4 weeks prior to
randomization. Patients who discontinued leflunomide and have had successful
chelation with 8 g of cholestyramine (3 times daily) for 11 days must wait 4 weeks
prior to randomization. Patients who discontinued leflunomide and did not have a
cholestyramine discontinuation period must wait 12 weeks after last dose of
leflunomide before randomization.
• Live or live-attenuated vaccine within 8 weeks prior to randomization, and killed
vaccines within 4 weeks prior to randomization
• History of any biologic agent causing B-cell depletion or targeting B-cells
8. Patient has a medical condition including one or more of the following:
• Uncontrolled diabetes mellitus, even after insulin treatment
• Uncontrolled hypertension at the discretion of the investigator
• Any other inflammatory or rheumatic disease, including but not limited to psoriatic arthritis, ankylosing spondylitis, spondyloarthritis, systemic lupus erythematosus, Lyme disease, or fibromyalgia, that may confound the evaluation of the effect of study drug
• History of any malignancy within the previous 5
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method