Tocilizumab Effect iN pOlymyalgia Rheumatica

Polymyalgia Rheumatica Clinical Trial

— TENOR  

Official title:

Phase II Open 24 Weeks Study to Evaluate Effect and Safety of Tocilizumab as the First Line Therapy in Subjects With Polymyalgia Rheumatica (PMR)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01713842
• Other study ID #: RB 11-075 TENOR
• Status: Completed
• Phase: Phase 2
• First received: September 17, 2012
• Last updated: February 10, 2015
• Start date: July 2012
• Est. completion date: October 2014

Study information

• Verified date: January 2015
• Source: University Hospital, Brest
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

Phase 1:

Patients are treated with infusions of Tocilizumab (TCZ) for 3 months. Clinical evaluation is performed using PMR-AS.

The PMR-AS is computed by summing the 5 variables after multiplying by 0.1 for weighting purposes: PMR-AS (activity scale = AS) = C reactive protein (CRP) (mg/dl) + patient scale (VASp) (0-10 scale) + physician scale (VASph) (0-10 scale) + morning stiffness(MST) [min]×0.1) + elevation of upper limbs (EUL) (0-3 scale).

At the end of the phase 1,the patients stop TCZ and entered in phase 2 at week 12.

Phase 2:

All the patients are included in the phase 2 and treated with glucocorticoid (GC)for 3 months. Two arms are possible according to the PMR-AS. Either the classical GC treatment (0.3mg/kg), either a low dose group of GC(0.15mg/kg) .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age between 50 years and 75 years included

• PMR-AS > 10

• PMR according to the Chuang criteria

• Evolving since less than 12 months

• Without Horton disease

• Able to understand and accept the study

• Agree to sign the inform consent form

• Without GC, or at least during 1 month and stop since 7 days before the inclusion.

• Stable dose of Nonsteroidal anti-inflammatory since 4 weeks before the inclusion.

• Birth controlled during all the study and 6 months after

Exclusion Criteria:

• Disagree to participated

• Unable to understand the study

• Participation to an other study in the 3 months before the inclusion

• Treated by GC at 0.3mg/kg/d in the past 7 days

• Less than 50 years old or more than 75 years old

• Uncontrolled dyslipidemia, high blood pressure or cardiovascular disease

• Histories of important allergy

• Historically positive test or test positive at screening for HIV-1 antibody, hepatitis B surface antigen, or hepatitis C antibody.

• Abnormal screening blood test : leukocyte count less than 3.5 × 109 cells/L, neutrophil count less than 2 × 109 cells/L, hemoglobin level less than 85 g/L, platelet count less than 100 × 109 cells/L, or hepatic aminotransferase or alkaline phosphatase levels greater than 3 times the upper limit of normal

• Other inflammatory rheumatic disease or connective disease

• Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to PMR (eg. Cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases)

• Current drug or alcohol abuse

• Patients treated with an immunosuppressive agents in the past 4 weeks

• Live/attenuated vaccine in the past 4 weeks

• Clinical symptoms of giant cell arteritis

• History of infection or infestation in the past 3 months

• Active tuberculosis

• Planned surgical procedure

• History of malignant neoplasm within the last 5 years, except for adequately treated cancer of the skin (basal or squamous cell)

• History or current tumoral hematological disease

• Severe allergic or anaphylactic reactions about one of the TCZ component

• Pregnant women during the study and six month after the end of the study

• Breast feeding mother

• Dysthyroidia

• Unstable treatment by statin in the past 3 months

• Parkinson disease

• Fibromyalgia

• Peripheric arthritis

• Articular chondrocalcinosis or hydorxyapatites rhumatisms

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Giant Cell Arteritis
• Polymyalgia Rheumatica

Intervention

Drug:
• TCZ
Tocilizumab at week 0, 4 and 8.

Locations

Country	Name	City	State
France	Brest University Hospital	Brest
France	Nantes University Hospital	Nantes
France	CHR d'Orléans	Orléans

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Brest	Chugai Pharmaceutical

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy at W12	PMR-AS at week 12	12 Weeks	No
Secondary	Safety and efficacy during the study	To maintain low disease activity (PMR-AS) in the low corticosteroid dose group from W12 to W24; On the inflammatory changes (synovitis, myositis, tenosynovitis aund bursitis) between baseline, W2 and 12 visualize by ultrasonography, MRI and Tep-Scan.; On sparing corticosteroid, with the comparison of the cumulative corticosteroid dosage beetwen the two groups of patients in the phase 2, W12 to 24.; On the circulating serum cytokines and immunoregulators (IL-6, IL-1, BLyS/BAFF, IL-6 receptor, gp130) and B cells receptors and on the phenotype of circulating T- and B-cells between baseline and W4 and 12 On inflammatory parameters (CRP and ESR) between baseline and W 2,4,8,12,16,20 and 24; On the quality of life of patients between baseline and W 4,12,16, 20 and 24; To evaluate the side-effects in relation to the use of Tocilizumab treatment. [ Time Frame: After first, second and third treatment and during follow up ]	Week 2,4,8,12,16,20 and 24	Yes