Tocilizumab Effect iN pOlymyalgia Rheumatica (TENOR)
Primary Purpose
Polymyalgia Rheumatica
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
TCZ
Sponsored by
About this trial
This is an interventional treatment trial for Polymyalgia Rheumatica focused on measuring Tocilizumab, Polymyalgia Rheumatica, Glucocorticotherapy, PMR-AS
Eligibility Criteria
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
Sites / Locations
- Brest University Hospital
- Nantes University Hospital
- CHR d'Orléans
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TCZ
Arm Description
Tocilizumab at week 0, week 4 and week 8 8mg/kg at each perfusion
Outcomes
Primary Outcome Measures
Efficacy at W12
PMR-AS at week 12
Secondary Outcome Measures
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 ]
Full Information
NCT ID
NCT01713842
First Posted
September 17, 2012
Last Updated
February 10, 2015
Sponsor
University Hospital, Brest
Collaborators
Chugai Pharmaceutical
1. Study Identification
Unique Protocol Identification Number
NCT01713842
Brief Title
Tocilizumab Effect iN pOlymyalgia Rheumatica
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Brest
Collaborators
Chugai Pharmaceutical
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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) .
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polymyalgia Rheumatica
Keywords
Tocilizumab, Polymyalgia Rheumatica, Glucocorticotherapy, PMR-AS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TCZ
Arm Type
Experimental
Arm Description
Tocilizumab at week 0, week 4 and week 8 8mg/kg at each perfusion
Intervention Type
Drug
Intervention Name(s)
TCZ
Intervention Description
Tocilizumab at week 0, 4 and 8.
Primary Outcome Measure Information:
Title
Efficacy at W12
Description
PMR-AS at week 12
Time Frame
12 Weeks
Secondary Outcome Measure Information:
Title
Safety and efficacy during the study
Description
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 ]
Time Frame
Week 2,4,8,12,16,20 and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Valérie DEVAUCHELLE, Pr
Organizational Affiliation
CHRU de Brest
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brest University Hospital
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Nantes University Hospital
City
Nantes
ZIP/Postal Code
44000
Country
France
Facility Name
CHR d'Orléans
City
Orléans
ZIP/Postal Code
45000
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
33301930
Citation
Carvajal Alegria G, Garrigues F, Bettacchioli E, Loeuille D, Saraux A, Cornec D, Devauchelle-Pensec V, Renaudineau Y. Tocilizumab controls bone turnover in early polymyalgia rheumatica. Joint Bone Spine. 2021 May;88(3):105117. doi: 10.1016/j.jbspin.2020.105117. Epub 2020 Dec 7.
Results Reference
derived
PubMed Identifier
30877202
Citation
Laporte JP, Garrigues F, Huwart A, Jousse-Joulin S, Marhadour T, Guellec D, Cornec D, Devauchelle-Pensec V, Saraux A. Localized Myofascial Inflammation Revealed by Magnetic Resonance Imaging in Recent-onset Polymyalgia Rheumatica and Effect of Tocilizumab Therapy. J Rheumatol. 2019 Dec;46(12):1619-1626. doi: 10.3899/jrheum.180958. Epub 2019 Mar 15.
Results Reference
derived
PubMed Identifier
26929219
Citation
Devauchelle-Pensec V, Berthelot JM, Cornec D, Renaudineau Y, Marhadour T, Jousse-Joulin S, Querellou S, Garrigues F, De Bandt M, Gouillou M, Saraux A. Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study. Ann Rheum Dis. 2016 Aug;75(8):1506-10. doi: 10.1136/annrheumdis-2015-208742. Epub 2016 Feb 29.
Results Reference
derived
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Tocilizumab Effect iN pOlymyalgia Rheumatica
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