Clinical Research Details

An Open-label, Randomized Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab (TCZ) Monotherapy or TCZ in Combination With Non-biologic DMARDs in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-biologic or Biologic DMARDs, Protocol Number ML22533

The purpose of this study is to assess the safety and tolerability of TCZ monotherapy or TCZ in combination with one or more of the approved background non-biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to current non-biologic or biologic DMARDs.

201942081909

750

Inclusion Criteria:
1. Participants must be at least 18 years old at the screening visit.
2. Diagnosis of moderate to severe active RA (swollen joint count [SJC] and tender joint count [TJC] =four) of =six months duration
3. Patients with an inadequate clinical response (investigator defined) or patients having safety/tolerability issues on stable dose(s) of non-biologic or biologic DMARDs (combination therapy or monotherapy)
4. If patients are receiving an oral corticosteroid, the prednisone dose or its equivalent must be =10 mg/day.
5. Willing to receive oral folate or leucovorin if taking methotrexate
Exclusion Criteria:
1. Major surgery (including joint surgery) within eight weeks prior to screening or planned major surgery within six months following randomization
2. History of autoimmune disease or inflammatory joint disease other than RA, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), gout, psoriatic arthritis, scleroderma, polymyositis or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty’s syndrome). Patients with interstitial pulmonary fibrosis and still able to tolerate MTX therapy are permitted. Sjögren’s Syndrome with RA is permitted.
3. Functional class IV as defined by the ACR Classification of Functional Status in RA
4. Treatment with rituximab within six months before screening
5. Treatment with IV gamma globulin, plasmapheresis or blood filtering column within six months, or any investigational cell-depleting therapies before baseline
7. Previous treatment with TCZ (an exception to this criterion may be granted for single-dose exposure upon application to the sponsor on a case-by-case basis)
9. Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation
10. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or GI disease (including complicated diverticulitis, ulcerative colitis or Crohn’s disease)
11. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, clinically significant abnormalities on chest x-ray (CXR) as determined by the investigator, hepatitis B and C and herpes zoster but excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within four weeks of screening, or oral antibiotics within two weeks prior to screening
12. Evidence of active malignant disease, malignancies diagnosed within the previous five years (including hematological malignancies and solid tumors, except non-melanoma skin cancer that has been excised and cured), or breast cancer diagnosed within the previous five years
13. Active TB requiring treatment within the previous three years
14. HIV-positive

Other specific inclusion and exclusion criteria are available from the Loyola Clinical Trials Office, (708) 216-2027.

You will receive an intravenous infusion (or IV) of four or eight mg/kg of TCZ every four weeks on an outpatient basis for a total of six infusions. The dose you receive is determined by what your present treatment (DMARD or biologic) for rheumatoid arthritis is.

If you are currently only taking one biologic (some examples are Abatacept, Infliximab, Etanercept, Adalimumab), you will receive TCZ at a dose of eight mg/kg.

All other patients who are taking a non-biologic DMARD or a combination of drugs for RA will be randomly assigned by a computer to one of two treatment regimens (after a phone call to a central system, you will be assigned to one of two treatment groups, like a flip of a coin). The two possible treatments that you could receive are as follows:

1. You will continue your current dose of allowed DMARDs and in addition you will be given TCZ at a dose of four mg/kg.

2. You will continue your current dose of allowed DMARDs and in addition you will be given TCZ at a dose of eight mg/kg

If you are not taking a biologic DMARD at the time of study entry, the randomization ratio of study drug dosages is 1:1; therefore, participants have a 50 percent chance of receiving TCZ at a dose of four mg/kg and a 50 percent chance of receiving TCZ at a dose of eight mg/kg.

Ruth Kadanoff, M.D.,Ph.D.

(708) 216-2026