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A randomized study to evaluate the efficacy of Tocilizumab to induce Remission and to spare Glucocorticoids in subjects with new-onset Polymyalgia Rheumatica.

Phase 1
Conditions
Polymyalgia rheumaticaPolymyalgia rheumatica is an inflammatory rheumatic disease that occurs primarily in the elderly with a peak incidence around 70 years of age. It is clinically characterized by shoulder girdle and hip pain and stiffness which impair raising arms and rising from a chair.
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Registration Number
EUCTR2016-004990-42-AT
Lead Sponsor
Medizinische Universität Wien, Universitätsklinik für Innere Medizin III, Klinische Abteilung für Rheumatologie
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
36
Inclusion Criteria

Diagnosis of PMR as confirmed by the investigator at screening and at baseline, fulfilment (also in retrospect) of the provisional 2012 ACR-EULAR classification criteria

Diagnosis of PMR established at, or up to 2 weeks before the screening visit

GC naïve or on GC treatment for a maximum of 2 weeks at screening with an initial dose between 12.5 and 25mg/day prednisone

Willing and able to receive oral prednisone 20mg/day at randomization and to follow a pre-specified tapering regimen

Willing to receive treatment for prevention of GC-induced bone loss

No evidence of active infection with Mycobacterium tuberculosis (screening performed according to national guidelines) and willing to take TB prophylaxis in case of evidence of latent TB

Willing and being able to understand and follow the study procedures

Male and female subjects agreeing to conduct efficient contraception (unless they have no childbearing potential)

Written informed consent.

Female and Male subjects from 18 years old and higher
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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

Exclusion Criteria

Evidence of GCA (cranial or large vessel) as indicated by unequivocal clinical symptoms (except PMR), imaging and/or biopsy results. Routine screening of eligible PMR patients for GCA with imaging methods or temporal artery biopsy is not recommended

GC treatment of PMR >2 weeks

Conditions other than PMR requiring continuous or intermittent treatment with oral or parenteral GCs or parenteral administration of GCs, unless the last exposure to GCs was >1 months before screening

Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis)

Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization

Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening

Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples include: CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20

Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline

Immunization with a live/attenuated vaccine within 4 weeks prior to baseline

Previous treatment with Tocilizumab (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis)

Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation

History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies

Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn´s disease)

Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT, AST, or both > 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin > ULN

Serum creatinine > 1.6 mg/dL (141 µmol/L) in female patients and > 1.9 mg/dL (168 µmol/L) in male patients. Patients with serum creatinine values exceeding limits may be eligible for the study, if their estimated glomerular filtration rates (GFR) are > 30

Total Bilirubin > ULN

Any history of recent serious bacterial, viral, fungal, or other opportunistic infections

Have serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C

Positive QuantiFERON TB test, history of Tuberculosis, or active Tuberculosis-infection, without at least 4 weeks of adequate therapy for Tuberculosis

Active infection with EBV as defined by EBV viral load > 10,000 copies per mL of whole blood

Any of the following hematologic abnormalities, confirmed by repeat tests:
a. White blood count < 3,000/µL or > 14,000/µL;
b. Lymphocyte count < 500/ µL;
c. Platelet count < 100,000/µL;
d. Hemoglobin < 8.0 g/dL; or
e. Neutrophil count < 2,000 cells/µL

Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening

Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation

Any medical or psychological condition that in the opinion of the Principal Investigator would interfere with safe completion of the trial

H

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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