Back to results

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

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

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

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

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

carine.salliot@chr-orleans.fr

First Name & Middle Initial & Last Name or Official Title & Degree

DESPUJOLS Aurélie

Phone

33 2 38 74 40 71

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

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

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

background

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

background

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

background

Learn more about this trial

Filling Bone Erosions: a Longitudinal Multicentric HR-pQCT Study of Subcutaneous Tocilizumab in Rheumatoid Arthritis

We'll reach out to this number within 24 hrs