Institutional Review Board, Hospital for Special Surgery
July 29, 2013
The safety of study participants is our top priority. The trial is approved and periodically reviewed by an Institutional Review Board (IRB), which includes doctors, administrators, ethicists, and members of the general public. The safety of clinical trials is reviewed by the U.S. Food and Drug Administration.
Before enrolling in a clinical trial, the investigator will explain the purpose of the trial, its expected benefits, any possible risks or side effects, and what your role will be. This is the time to ask questions! If you want to join the trial, you must sign the informed consent documents. You can leave a clinical trial at any time without penalty.
For further information, see Understanding Clinical Trials.
Jessica k. Gordon, MD
Mary Crow, MD
Lindsay Lally, MD
Steven Benkert, R. Ph
Uzunma Udeh, BA
Nina Paddu, BA
The purpose of this study is to see whether a medication called Tocilizumab (Actemra®) is an effective and safe addition to steroids in the treatment of PMR. Tocilizumab is a medication already on the market that has been FDA approved in the US and Japan for the treatment of rheumatoid arthritis, and in Japan it is also approved for certain types of juvenile idiopathic arthritis (which is like rheumatoid arthritis in children) and Castleman’s disease (which is a rare disease that causes enlarged lymph nodes). It is not FDA approved to treat polymyalgia rheumatica at this time. It will be given as an intravenous infusion once a month for a treatment period of one year. Experiments done on the blood of patients with PMR show one particular cytokine or small molecule that circulates throughout your body, interleukin-6, to be elevated in this disease. Tocilizumab is a medication that is designed to specifically block this cytokine.
Tocilizumab has not been used before to treat PMR. This study is being done to see if this medication is safe and effective in treating this disease. If you enroll in this study, you will be treated with Tocilizumab once a month by intravenous infusion, in addition to steroid therapy. In this trial, the steroid dosage will be decreased much more quickly than what is done in routine clinical practice; we plan to decrease your steroids so that you are no longer taking them after four months, which is much shorter than the one to two years of steroids often used to treat PMR. We will watch you closely for signs and symptoms of PMR and if they recur, we will increase your steroids to control your symptoms. If you can successfully stop steroids, this would indicate that Tocilizumab is helpful in treating PMR. Your overall participation in this study will be over a period of 15 months.
• Criteria for Target Population
o Patients must meet the following inclusion criteria to be eligible for study entry:
o Diagnosed with polymyalgia rheumatica as defined by the Healey Criteria for classification of the disease and enrolled within one month of diagnosis.
? Healey Criteria defined by:
• Age greater than 50.
• Erythrocyte sedimentation rate greater than 40 mm per hour.
• Persistent pain (greater than or equal to one month) involving 2 of 3 areas (neck, shoulders, or pelvic girdle).
• Morning stiffness lasting more than one hour.
• Rapid response to prednisone, 20 mg daily or its equivalent, or less.
o Absence of signs or symptoms of other connective tissue disease.
• General Inclusion Criteria Considerations
o Able and willing to give written informed consent and comply with the requirements of the study protocol.
o Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for at least 6 months after completion of treatment.
o Subjects must be willing to report pregnancies (females and male’s partners) that occur at any time during the trial
o Negative serum pregnancy test for women of child bearing potential (WOCBP). Women who are not of childbearing potential are excluded from this criterion. See below for definitions.
o WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:
o Amenorrhea = 12 consecutive months without another cause
o For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level = 35 mIU/mL.
o Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence, or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential
• Patients will be excluded from the study based on the following criteria:
o Symptoms or diagnosis of temporal arteritis, including headache, jaw claudication, hyperesthesia of scalp, abnormal palpated temporal artery, visual disturbances, temporal artery biopsy positivity
o Concurrent rheumatoid arthritis
o Presence of rheumatoid factor and CCP
o Other inflammatory arthritis or other connective tissue diseases, such as but not limited to systemic lupus erythematosus, systemic sclerosis, vasculitis, polymyositis, dermatomyositis, mixed connective tissue disease
o Treatment of polymyalgia rheumatica with more than 20mg of daily prednisone or its equivalent at the time of screening
o Treatment of more than 30mg of daily prednisone or its equivalent since diagnosis. Treatment with 21-30mg of daily prednisone or its equivalent since diagnosis for more than 2 weeks.
o More than 4 weeks of corticosteroid therapy prior to enrollment
o History of bowel perforation within the past five years.
o Active diverticulitis.
o Pre-existing or recent onset demyelinating disorders