Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of Subcutaneous Tocilizumab in Rheumatoid Arthritis (REPAIR)
Primary Purpose
Rheumatoid Arthritis
Status
Recruiting
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
subcutaneous tocilizumab
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring subcutaneous tocilizumab, High Resolution peripheral QCT (HR-pQCT), bone erosion, bone microarchitecture, rheumatoid arthritis
Eligibility Criteria
Inclusion Criteria:
- Active RA, < 10 years disease duration, diagnosed according to the ACR-EULAR 2010 classification criteria
- DAS 28 superior or equal to 3.2 despite DMARD or biological treatment (other than tocilizumab)
- Superior or equal to one joint erosion at the right or left MCP 2, 3 on X-rays
- Oral corticosteroid ≤ 10 mg/day prednisone or equivalent stable for at least one month
- RA patients eligible to subcutaneous Tocilizumab monotherapy
Exclusion Criteria:
Treatment with zoledronic acid or denosumab (less than one year)
- Intra-articular injection of corticosteroids at the MCP in the previous three months
- Tocilizumab contra-indications in accordance with SPC (Summary of Product Characteristics) :Hypersensitivity to the active substance or to any of the excipients Active, severe infections including active tuberculosis Diverticulitis Active hepatic disease and hepatic Impairment including viral hepatitis Elevated Alanine Aminotransferase or Aspartate Aminotransferase >5×ULN Absolute neutrophil count < 0.5 × 10 exp 9 /L Platelet count < 50×10 exp 3 /μL,
General:
- Absence of informed consent
- Prior or planned joint surgery of the hands which might impact the interpretation of imaging assessments.
Sites / Locations
- Hopital Edouard HERIOTRecruiting
- CHR d'ORLEANSRecruiting
- Hopital Nord CHU de SAint ETIENNERecruiting
- Chu ToulouseRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Roactemra
Arm Description
subcutaneous tocilizumab
Outcomes
Primary Outcome Measures
Bone erosion change after 12 months of subcutaneous tocilizumab
changes of width measured by HRpQCT.
Bone erosion change after 12 months of subcutaneous tocilizumab
changes of depth measured by HRpQCT.
Bone erosion change after 12 months of subcutaneous tocilizumab
changes of volume measured by HRpQCT.
Secondary Outcome Measures
Associated factors with erosion changes assessed by HRqQCT
Number of participants with associated factors with erosion changes by HRpQCT (Associated therapeutic, clinical and biological response )ultrasound ...)
Effect of 12 months of tocilizumab on bone density in the PR
Changes of Bone mineral density by DXA at the lumbar spine and proximal femur
Effect of Tocilizumab on synovitis/tenosynovitis assessed by US and agreement with disease activity scores
Correlation Between clinical activity measured by various indices (Disease Activity Score 28, Clinical Disease Activity Iindex , Simplify Disease Activity Index , American College of Rheumatology - European League against Rheumatism: ACR EULAR) and ultrasound data.
Effect of 12 months of tocilizumab on bone microarchitecture in the PR
changes of bone microarchitecture by tibia HRpQCT
Full Information
NCT ID
NCT02765074
First Posted
April 19, 2016
Last Updated
June 14, 2023
Sponsor
Centre Hospitalier Régional d'Orléans
Collaborators
Rennes University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02765074
Brief Title
Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of Subcutaneous Tocilizumab in Rheumatoid Arthritis
Acronym
REPAIR
Official Title
Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of 12 Months Subcutaneous Tocilizumab in Rheumatoid Arthritis Phase IV Prospective Multicentrique Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 30, 2016 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Régional d'Orléans
Collaborators
Rennes University Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease mediated by the production of several cytokines, which leads to the destruction of bone and cartilage tissue in multiple joints and to bone loss. Conventional radiographs (CR) are considered as the gold standard for diagnosis and follow up of joint changes in RA. But this method has low sensitivity to detect early erosive changes and is unable to evaluate periarticular bone loss.
High Resolution peripheral QCT (HRpQCT) enables the detection of erosions less than 0.5 mm in width or depth at metacarpo-phalangeal (MCP) joints. Using 3-D high resolution analysis of cortical bone erosions, this one is also able to evaluate the volumes of erosion and the evolution under treatments IL6 (6- interleukin) plays a major role in inflammatory process and bone damages related to RA. Tocilizumab (TCZ) is a humanized anti-IL-6R monoclonal antibody, developed and investigated in several clinical trials in RA. This biotherapy, in association with methotrexate (MTX) or given in monotherapy, is efficient in RA with inadequate response to MTX or anti-TNF b (tumor necrosis factor). TCZ reduces dramatically systemic inflammation, structural progression and improves clinical symptoms and quality of life.
Tocilizumab may help reducing bone erosions, periarticular osteopenia and systemic bone loss.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
subcutaneous tocilizumab, High Resolution peripheral QCT (HR-pQCT), bone erosion, bone microarchitecture, rheumatoid arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Roactemra
Arm Type
Experimental
Arm Description
subcutaneous tocilizumab
Intervention Type
Drug
Intervention Name(s)
subcutaneous tocilizumab
Other Intervention Name(s)
Roactemra
Intervention Description
162 mg subcutaneous, once a week during 12 months
Primary Outcome Measure Information:
Title
Bone erosion change after 12 months of subcutaneous tocilizumab
Description
changes of width measured by HRpQCT.
Time Frame
baseline and 12 months
Title
Bone erosion change after 12 months of subcutaneous tocilizumab
Description
changes of depth measured by HRpQCT.
Time Frame
baseline and 12 months
Title
Bone erosion change after 12 months of subcutaneous tocilizumab
Description
changes of volume measured by HRpQCT.
Time Frame
baseline and 12 months
Secondary Outcome Measure Information:
Title
Associated factors with erosion changes assessed by HRqQCT
Description
Number of participants with associated factors with erosion changes by HRpQCT (Associated therapeutic, clinical and biological response )ultrasound ...)
Time Frame
baseline, 3 months, 12 months
Title
Effect of 12 months of tocilizumab on bone density in the PR
Description
Changes of Bone mineral density by DXA at the lumbar spine and proximal femur
Time Frame
baseline, 12 months
Title
Effect of Tocilizumab on synovitis/tenosynovitis assessed by US and agreement with disease activity scores
Description
Correlation Between clinical activity measured by various indices (Disease Activity Score 28, Clinical Disease Activity Iindex , Simplify Disease Activity Index , American College of Rheumatology - European League against Rheumatism: ACR EULAR) and ultrasound data.
Time Frame
Predictors baseline, 1 and 3 months of clinical remission and / or ultrasound at 6 and 12 months
Title
Effect of 12 months of tocilizumab on bone microarchitecture in the PR
Description
changes of bone microarchitecture by tibia HRpQCT
Time Frame
baseline, 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Active RA, < 10 years disease duration, diagnosed according to the ACR-EULAR 2010 classification criteria
DAS 28 superior or equal to 3.2 despite DMARD or biological treatment (other than tocilizumab)
Superior or equal to one joint erosion at the right or left MCP 2, 3 on X-rays
Oral corticosteroid ≤ 10 mg/day prednisone or equivalent stable for at least one month
RA patients eligible to subcutaneous Tocilizumab monotherapy
Exclusion Criteria:
Treatment with zoledronic acid or denosumab (less than one year)
Intra-articular injection of corticosteroids at the MCP in the previous three months
Tocilizumab contra-indications in accordance with SPC (Summary of Product Characteristics) :Hypersensitivity to the active substance or to any of the excipients Active, severe infections including active tuberculosis Diverticulitis Active hepatic disease and hepatic Impairment including viral hepatitis Elevated Alanine Aminotransferase or Aspartate Aminotransferase >5×ULN Absolute neutrophil count < 0.5 × 10 exp 9 /L Platelet count < 50×10 exp 3 /μL,
General:
Absence of informed consent
Prior or planned joint surgery of the hands which might impact the interpretation of imaging assessments.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
SALLIOT Carine, MD
Phone
33 2 38 22 99 22
Email
carine.salliot@chr-orleans.fr
First Name & Middle Initial & Last Name or Official Title & Degree
DESPUJOLS Aurélie
Phone
33 2 38 74 40 71
Email
aurelie.despujols@chr-orleans.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
SALLIOT Carine, MD
Organizational Affiliation
CHR ORLEANS
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
LESPESSAILLES Eric, MD, PhD
Organizational Affiliation
CHR ORLEANS
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
CANTAGREL Alain, MD, PhD
Organizational Affiliation
CHU Toulouse
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
CHAPURLAT Roland, MD, PhD
Organizational Affiliation
CHU LYON
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
MAROTTE Hubert, MD, PhD
Organizational Affiliation
HOPITAL NORD SAINT ETIENNE
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Edouard HERIOT
City
Lyon
ZIP/Postal Code
69437
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
CHAPURLAT Roland, PUPH
Facility Name
CHR d'ORLEANS
City
Orleans
ZIP/Postal Code
45067
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
SALLIOT Carine
Facility Name
Hopital Nord CHU de SAint ETIENNE
City
Saint Etienne
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MAROTTE Hubert
Facility Name
Chu Toulouse
City
Toulouse
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adeline RUYSSEN-WITRAND, Dr
Email
ruyssen-witrand.a@chu-toulouse.fr
First Name & Middle Initial & Last Name & Degree
Adeline RUYSSEN-WITRAND, Dr
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
16189253
Citation
Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2005 Dec;90(12):6508-15. doi: 10.1210/jc.2005-1258. Epub 2005 Sep 27.
Results Reference
background
PubMed Identifier
20112404
Citation
Stach CM, Bauerle M, Englbrecht M, Kronke G, Engelke K, Manger B, Schett G. Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high-resolution computed tomography. Arthritis Rheum. 2010 Feb;62(2):330-9. doi: 10.1002/art.27252.
Results Reference
background
PubMed Identifier
20525847
Citation
Fouque-Aubert A, Boutroy S, Marotte H, Vilayphiou N, Bacchetta J, Miossec P, Delmas PD, Chapurlat RD. Assessment of hand bone loss in rheumatoid arthritis by high-resolution peripheral quantitative CT. Ann Rheum Dis. 2010 Sep;69(9):1671-6. doi: 10.1136/ard.2009.114512. Epub 2010 Jun 4.
Results Reference
background
PubMed Identifier
24614646
Citation
Ellouz R, Chapurlat R, van Rietbergen B, Christen P, Pialat JB, Boutroy S. Challenges in longitudinal measurements with HR-pQCT: evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility. Bone. 2014 Jun;63:147-57. doi: 10.1016/j.bone.2014.03.001. Epub 2014 Mar 12.
Results Reference
background
PubMed Identifier
19019887
Citation
Moller Dohn U, Boonen A, Hetland ML, Hansen MS, Knudsen LS, Hansen A, Madsen OR, Hasselquist M, Moller JM, Ostergaard M. Erosive progression is minimal, but erosion healing rare, in patients with rheumatoid arthritis treated with adalimumab. A 1 year investigator-initiated follow-up study using high-resolution computed tomography as the primary outcome measure. Ann Rheum Dis. 2009 Oct;68(10):1585-90. doi: 10.1136/ard.2008.097048. Epub 2008 Nov 19.
Results Reference
background
PubMed Identifier
21622765
Citation
Finzel S, Rech J, Schmidt S, Engelke K, Englbrecht M, Stach C, Schett G. Repair of bone erosions in rheumatoid arthritis treated with tumour necrosis factor inhibitors is based on bone apposition at the base of the erosion. Ann Rheum Dis. 2011 Sep;70(9):1587-93. doi: 10.1136/ard.2010.148395. Epub 2011 May 27.
Results Reference
background
PubMed Identifier
19435723
Citation
Dohn UM, Ostergaard M, Bird P, Boonen A, Johansen JS, Moller JM, Hansen MS. Tendency towards erosive regression on magnetic resonance imaging at 12 months in rheumatoid arthritis patients treated with rituximab. Ann Rheum Dis. 2009 Jun;68(6):1072-3. doi: 10.1136/ard.2008.098962. No abstract available.
Results Reference
background
PubMed Identifier
20980282
Citation
Dohn UM, Ejbjerg B, Boonen A, Hetland ML, Hansen MS, Knudsen LS, Hansen A, Madsen OR, Hasselquist M, Moller JM, Ostergaard M. No overall progression and occasional repair of erosions despite persistent inflammation in adalimumab-treated rheumatoid arthritis patients: results from a longitudinal comparative MRI, ultrasonography, CT and radiography study. Ann Rheum Dis. 2011 Feb;70(2):252-8. doi: 10.1136/ard.2009.123729. Epub 2010 Oct 26.
Results Reference
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PubMed Identifier
22586162
Citation
Finzel S, Rech J, Schmidt S, Engelke K, Englbrecht M, Schett G. Interleukin-6 receptor blockade induces limited repair of bone erosions in rheumatoid arthritis: a micro CT study. Ann Rheum Dis. 2013 Mar;72(3):396-400. doi: 10.1136/annrheumdis-2011-201075. Epub 2012 May 14.
Results Reference
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PubMed Identifier
20039425
Citation
Garnero P, Thompson E, Woodworth T, Smolen JS. Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum. 2010 Jan;62(1):33-43. doi: 10.1002/art.25053.
Results Reference
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Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of Subcutaneous Tocilizumab in Rheumatoid Arthritis
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