Polymyalgia rHeumatica MedDRA version: 19.0 Level: PT Classification code 10036099 Term: Polymyalgia rheumatica System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Tocilizumab
Product Name: RoActemra
Pharmaceutical Form: Concentrate and solvent for solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration
Sponsors
CHRU DE BREST
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Age older than 50 years -Having previously -Fulfilled the Chuang criteria -Be successfully treated with GCs = 15mg (CRP = 10 mg/l or ESR = 20 mm before GCs treatment and 10 -Absence of signs or symptoms of other musculoskeletal or connective tissue conditions -Able to give informed consent -Concomitant treatments with méthotrexate or hydroxychloroquine are permitted if stable dose since 3 months. 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
Exclusion criteria
Exclusion criteria: General Exclusion Criteria: - Clinical symptoms of giant cell arteritis - Uncontrolled dyslipidemia, high blood pressure or cardiovascular disease - History of major organ or haematopoietic stem cell/marrow transplant - Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to PMR - Planned surgical procedure within 12 months after randomization. - History of malignant neoplasm within the last 5 years. - Current active infection Detailed exclusion criteria related to prior or concomitant therapy, general safety and laboratory data: Exclusions Related to Prior or Concomitant Therapy - Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to Campath (alemtuzumab), anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20 - Treatment with IV gamma globulin or plasmapheresis within 6 months of baseline - Previous treatment with alkylating agents, such as chlorambucil, or with total lymphoid irradiation - Previous treatment with TCZ - Immunization with a live/attenuated vaccine within = 4 weeks prior to baseline - Treatment with cyclosporine A, azathioprine, or MMF within 4 weeks of baseline - Treatment with etanercept within 2 weeks; infliximab, certolizumab, golimumab, abatacept, or adalimumab within 8 weeks; or anakinra within 1 week of baseline - Previous treatment with tofacitinib - Treatment with cyclophosphamide within 6 months of baseline Exclusions Related to General Safety - History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies or to prednisone - Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), psychiatric, osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, or gastrointestinal (GI) disease - History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose a patient to perforations - Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail beds) - Active TB requiring treatment within the previous 3 years Patients should be screened for latent TB and, if positive, treated according to local practice guidelines prior to initiating TCZ treatment. Patients treated for TB with no recurrence within 3 years and patients treated for latent TB within 3 years are eligible. - Primary or secondary immunodeficiency (history of or currently active) - Pregnant women and females who are breastfeeding - Female of childbearing potential must have a negative serum pregnancy test within 28 days of randomization. Females of child-bearing potential may participate in this trial only if using a reliable means of contraception (e.g. physical barrier (patient and partner), contraceptive pill or patch, spermicide and barrier, or IUD) during study treatment and for minimum of 3 months after last dose of TCZ. - Males of reproductive potential who are not willing to use an effective method of contraception, such as condom, sterilization, or true abstinence throughout study and for a minim
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the ability of tocilizumab in comparison to placebo to decrease GCs (prednisone or prednisolone) and to maintain low disease activity at week 24 in steroid dependent PMR patients ;Secondary Objective: - Tolerance of tocilizumab and GCs - Absence of flare (PMR-AS>17) and remission from W24 to W32 in both arms - PMR-AS in tocilizumab arm versus placebo - PMR-AS using ESR in tocilizumab arm versus placebo - Cost/efficacy of tocilizumab arm in comparison to placebo and GCs - Quality of life (SF-36) and HAD in tocilizumab arm versus placebo - Cumulative doses of GCs in tocilizumab and placebo arms - Evaluation of synovitis and tenosynovitis in shoulders and hips using ultrasound in mode B and Doppler -Osteodensitometry (lumbar and hip sites) in Tocilizumab arm versus placebo - Biological markers in tocilizumab and placebo arms: Interleukin-6, TGF-ß, B cells subpopulations, CRP, pyridinoline, telopeptide ;Primary end point(s): Low disease activity (PMR-AS<10) with steroid independence (GCs =5 mg (absolute value) or decrease = 10 mg from week 0 to week 24).;Timepoint(s) of evaluation of this end point: week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Adverse events following SOC classification in both arms - Proportion of patients with (PMR-AS>17) from W24 to W32 in both arm - PMR-AS (inclusion and W0, W4, W8, W12, W16, W20, W24 and W32) and proportion of patients with PMR-AS < 1.5; 10;17. - Cost/efficacy of tocilizumab - Cumulative dosages of GCs at Week 32 - Ultrasound Scoring of synovitis and tenosynovitis (mode B and Doppler) at inclusion and W 12, 24 and 32 - bone mass density (lumbar and hip sites) (at inclusion and W32) - Level of biological markers in tocilizumab and placebo arms: Interleukine-6, TGF-ß, B cells sub populations, pyridinolins and telopeptides (at inclusion, W8, W16, W24, W32) ;Timepoint(s) of evaluation of this end point: week 32 | — |
Countries
France
Contacts
Public ContactSPONSOR
CHRU DE BREST
Outcome results
None listed