A Phase 2, 2-Part, Multicenter, Randomized, Double-blind,Parallel-group, Placebo-controlled, Proof-of-concept, dose-findingStudy Evaluating the Efficacy and Safety of CNTO 136Administered Subcutaneously in Subjects with Active RheumatoidArthritis Despite Methotrexate Therapy - Not available
- Conditions
- Rheumatoid ArthritisMedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis
- Registration Number
- EUCTR2007-006603-20-HU
- Lead Sponsor
- Centocor B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 190
1. Men or women 18 years of age or older.
2. Have a diagnosis of RA (according to the revised 1987 criteria of the ARA; Arnett et al, 1988) for at least 4 months prior to screening.
3. Are currently being treated with MTX at a dose of =15 mg/week for at least
4 months prior to screening and with an inadequate response to therapy according to the investigator. MTX doses of 10 or 12.5 mg/week are permitted only if 15 mg/week has not been tolerated. MTX route of administration and dose (not to exceed 25 mg/week) should be stable for at least 6 weeks prior to the first administration of the study agent, and the subjects should have no serious toxic side effects attributable to MTX.
4. Have active RA as defined, for the purpose of this study, by persistent disease activity with at least 6 swollen and 6 tender joints at the time of screening and at baseline and must be anti-CCP antibody-positive or RF positive at screening.
5. Screening CRP = 1.0 mg/dL (SI: 10 mg/L)
6. If using oral corticosteroids, must be on a stable dose equivalent to =10 mg/day of prednisone for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, the subject must not have received oral corticosteroids for at least 2 weeks prior to the first administration of study agent.
7. If using NSAIDs or other analgesics for RA, must be on a stable dose for at least 2 weeks prior to the first administration of study agent.
8. If using sulfasalazine (SSZ), hydroxychloroquine (HCQ), or chloroquine (CQ), should have started treatment at least 3 months prior to the first administration of study agent and should have no serious toxic side effects attributable to the disease modifying antirheumatic drug (DMARD). If using SSZ, HCQ, or CQ, must also be on a stable dose for at least 4 weeks prior to the first administration of study agent.
If currently not using SSZ, HCQ, or CQ, must have not received these DMARDs
for at least 4 weeks prior to the first administration of the study agent.
9. Women of childbearing potential or men capable of fathering children must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization) during the study and for 6 months after receiving the last administration of study agent. Female subjects of childbearing potential must test negative for pregnancy.
10. Are willing and able to adhere to the study visit schedule and other protocol requirements.
11. Are capable of providing informed consent, which must be obtained prior to any study-related procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Have inflammatory diseases other than RA, including but not limited to psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus, or Lyme disease that might confound the evaluation of the benefit of CNTO 136 therapy in arthritis.
2. Have a marked baseline prolongation of the time between the beginning of the QRS complex and the end of the T-wave, adjusted for heart rate (normal 350-440 milliseconds) (QTc) interval, a history of risk factors for Torsade de Pointes such as persistent hypokalemia or family history of long QT syndrome; or a history of second or third-degree heart block.
3. Are infected with HIV, hepatitis B, or hepatitis C. (part B only)
4. Have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
5. Have a history of, or ongoing chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (eg, recurrent pyelonephritis, chronic nonremitting cystitis), an open, draining, or infected skin wound, or an ulcer.
6. Have had a serious infection (including but not limited to hepatitis, pneumonia, sepsis, or pyelonephritis), or have been hospitalized for an infection, or have been treated with IV antibiotics for an infection within 2 months prior to the first administration of study agent. Less serious infections (eg, acute upper respiratory tract infection, simple urinary tract infection) need not be considered exclusionary at the discretion of the investigator.
7. Have any known malignancy or have a history of malignancy within the previous 5 years (with the exception of a nonmelanoma skin cancer that has been treated with no evidence of recurrence for at least 3 months).
8. Have a history of active TB prior to screening; or have signs and symptoms suggestive of active TB; or have had recent close contact with a person with active TB.
9. Have a chest radiograph, both posterior-anterior and lateral views, taken within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection.
10. History or presence of any uncontrolled psychiatric or emotional disorder, (including drug and alcohol abuse with in the past 3 years), that might prevent the successful completion of the study.
11. Exclusionary labs include: a. Hemoglobin < 8.5 g/dL (SI: < 85 g/L) or < 5.3 mmol/L. b. WBC < 3.5 x 10^3 cells/µL (SI: < 3.5 x 10^9 cells/L). c. Neutrophils < 1.5 x 10^3 cells/µL (SI: < 1.5 x 10^9 cells/L). d. Platelets < 140 x 10^3 cells/µL (SI: < 140 x 10^9 cells/L). e. ALT and AST levels > 1.5 times the ULN for the central laboratory conducting the test. f. Serum creatinine = 2.0 mg/dL (SI: 177 µmol/L).
12. Has a known allergy to any of the following: dextrose, sucrose, L-histidine, L-histidine monohydrochloride, Polysorbate 80.
13. Previous serious hypersensitivity reaction to monoclonal antibodies.
14. Have used biologic agent(s) targeted at reducing TNF.
15. Have received tocilizumab (anti-IL-6 receptor).
16. Have received cytotoxic drugs such as cyclophosphamide, chlorambucil, nitrogen
mustard, or other alkylating agents.
17. Have received a B-cell depleting biologic therapy (eg, rituximab) within 12 months of first study agent administration, or persistent evidence of B-cell depletion at the ti
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