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Abatacept in earLy Onset Polymyalgia Rheumatica: Study ALORS (ALORS)

Primary Purpose

Polymyalgia Rheumatica

Status
Active
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Abatacept
Placebos
Sponsored by
University Hospital, Brest
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polymyalgia Rheumatica

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age older than 50 years
  • Fulfilling ACR/EULAR criteria
  • Disease duration≤6 months
  • No steroid since 2 weeks prior randomization
  • PMR-AS≥ 17
  • Absence of signs or symptoms of other musculoskeletal or connective tissue conditions
  • Able to give informed consent
  • Concomitant treatments with methotrexate or hydroxychloroquine are not permitted.

Exclusion Criteria:

  • Clinical symptoms of giant cell arteritis
  • Uncontrolled high blood pressure or cardiovascular disease
  • Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to PMR
  • Planned surgical procedure or medical history, blood abnormalities or any clinical condition that compromises inclusion
  • History of malignant neoplasm within the last 5 years.
  • Current active infection not controlled
  • Detailed exclusion criteria related to prior or concomitant therapy, general safety and laboratory data are reported in the protocol

Sites / Locations

  • CHRU de Brest
  • CH Le Mans
  • CH de Morlaix
  • CH St-Malo
  • CHU Strasbourg

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental group

Control group

Arm Description

Subcutaneous abatacept every weeks during 3 months (W0 to W11). Then, at W12, if PMR-AS>10, they will receive GCs according to the PMR-AS (PMR-AS≤10: no GCs, PMR-AS between 10-20: 10mg/day, PMR-AS between 21-30: GCs at 15mg/d and if PMR-AS> 30: 20mg/d). Dosage of GCs will be decreased between W16 and W24 (1mg every week) in each arm according to PMR-AS (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose). If PMR-AS ≤10, the patients wont receive any treatment until a flare.

Subcutaneous placebo every week during 3 months (W0 to W11). Then, at week 12, if PMR-AS>10, they will receive GCs according to the PMR-AS (PMR-AS≤10: no GCs, PMR-AS between 10-20: 10mg/day, PMR-AS between 21-30: GCs at 15mg/d and if PMR-AS> 30: 20mg/d). Dosage of GCs will be decreased between W16 and W24 (1mg every week) in each arm according to PMR-AS (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose). If PMR-AS ≤10, the patients won't receive any treatment until a flare.

Outcomes

Primary Outcome Measures

Following of one biological parameter (CRP)
The Polymyalgia Rheumatica Activity score is evaluated with a biological parameter named CRP.

Secondary Outcome Measures

Emergence of adverse events (Safety and tolerability)
The safety is evaluated with the adverse events in both arms
Following of the Polymyalgia Rheumatica Activity score
The Polymyalgia Rheumatica Activity score is evalauted with CRP and without CRP. The activity of Polymyalgia Rheumatica is evaluated using the Polymyalgia Rheumatica Activity score (PMR-AS), a disease activity score based on morning stiffness, ability to elevate the upper limbs, physician's global disease assessment and pain assessment measured by the patient using VAS, and the C-reactive protein (CRP) level. The PMR-AS is considered as relevant to define relapse and remission but also to decide if treatment have to be decreased, unchanged or increased (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose)
Medical resource evaluation
The cost of the utilization of Abatacept is evaluated
Following of the cumulative dosages of Glucocorticoids
The cumulative dosages of GCs is evaluated
The flare of the Polymyalgia Rheumatica
The flare of the Polymyalgia Rheumatica will be evaluate by the activity of Polymyalgia Rheumatica which is evaluated using the Polymyalgia Rheumatica Activity score ( (PMR-AS) which is not a scale but a score based on morning stiffness, ability to elevate the upper limbs, physician's global disease assessment and pain assessment measured by the patient using VAS, and the C-reactive protein (CRP) level. The PMR-AS is considered as relevant to define relapse and remission but also to decide if treatment have to be decreased, unchanged or increased (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose).
Following of the medical exam using the ultrasound Scoring
The ultrasound scoring of synovitis and tenosynovitis is evaluated
Evaluation of FDG uptake using TEP-scanner in RegiOns of Interest
The FDG uptake is evalated with TEP-scanner using the FDG radiotracer
Following the proportion of patients relapse
The proportion of patients relapse or remission is evaluated with the Polymyalgia Rheumatica Activity score>17
Biological markers
The level of biological markers and cell subpopulations with the result of blood test is evaluated. The list of biological markers is (Interleukin, cytokines, immune cells)
Following of the quality of life
The Short Form 36 (SF36) is used to evaluate the quality of life. The SF36 scale includes 36 items divided into 8 dimensions (physical functioning, role limitations related to physical health, physical pain, general health, vitality [energy / fatigue].
Following of the quality of life
The scale EuroQol 5 dimensions (EDQ5) is used to evaluate the quality of life. The EQ-5D scale is a standardised measure of health status to provide a simple, generic measure of health for clinical and economic appraisal, whih is divided by the EQ-5D descriptive system (mobility, self care, usual activities, pain/discomfort, anxiety/depression) and the EQ Visual Analogue scale (EQ VAS). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems).
Following of the quality of life
The Hospital Anxiety and the Depression scale (HAD) is used to evaluate the quality of life. The HAD scale has 14 items rated from 0 to 3 with 7 questions relate to anxiety and 7 others to the depressive dimension.

Full Information

First Posted
July 11, 2018
Last Updated
May 19, 2022
Sponsor
University Hospital, Brest
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT03632187
Brief Title
Abatacept in earLy Onset Polymyalgia Rheumatica: Study ALORS
Acronym
ALORS
Official Title
To Demonstrate the Ability of Abatacept in Comparison to Placebo to Obtain a Low Disease Activity [PMR-AS (CRP) Lower or Equal to 10] Without GCs (Prednisone or Prednisolone) at Week 12 in Early Onset PMR Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 13, 2018 (Actual)
Primary Completion Date
October 21, 2021 (Actual)
Study Completion Date
July 21, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Brest
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Polymyalgia rheumatic (PMR) is a frequent inflammatory disease. It affects the elderly, with peak incidences at the age of 70 to 80 years; an age >50 years or older, is considered a criterion for the diagnosis. Polymyalgia rheumatica occurs at a frequency that is 3 to 10 times that of giant-cell arteritis. Disease risk varies according to race and geographic region. The incidence is highest among whites in northern European populations (about 20 cases per 100,000 persons older than 50 years of age); it is lower in southern European populations (about 10 cases per 100,000).The diagnosis is based on established ACR/EULAR classification criteria. Long term low-dose glucocorticoid (GCs) (prednisone or prednisolone started at 15 to 20 mg/day progressively tapered) is the mainstay of the treatment. The activity of PMR is evaluated using the PMR-AS, a disease activity score based on morning stiffness, ability to elevate the upper limbs, physician's global disease assessment and pain assessment measured by the patient using VAS, and the C-reactive protein (CRP) level. The PMR-AS is considered as relevant to define relapse and remission but also to decide if treatment have to be decreased, unchanged or increased (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose).. Comorbidity in PMR are due to GCs and 30% of the patients underwent a relapse when tapering GCs. If the investigators able to start prednisone at a lower dosage (i.e. 8 mg then tapered for 3 to 4 months), the cumulative dosage of steroid would not have major side effects but it is not possible without new therapeutic agents. The TENOR study (Tolerance and Efficacy of tocilizumab iN pOlymyalgia Rheumatica), a phase 2 study, demonstrated efficacy of tocilizumab as first line treatment in PMR without GCs and its ability to spare GCs. This was the first study demonstrating that a biologic may improve PMR without steroid, and that also showed that a short treatment by biologic followed by a low dose GCs therapy may be a new concept in the treatment of PMR. Molecular studies in GCA and PMR suggest that dendritic cells initiate the pathogenic cascade and recruit T cells. Two major immune-response networks have been identified related to type 1 helper T-cell (Th1) and to helper T-cell (Th17). Abatacept is comprised of the ligand-binding domain of CTLA4 plus modified Fc domain derived from IgG1. By containing CTLA4, abatacept blocks the engagement of CD28 with its ligand, thereby inhibiting T cell activation. It has recently demonstrated its efficacy in Granulomatosis with polyangiitis (GPA) but also in giant cell arteritis (GCA). Due to its good safety profile in rheumatoid arthritis and its potential to modulate T cell activation and derived cytokines, abatacept is an attractive agent to investigate in patients with PMR. In this randomized prospective placebo controlled study, the objective is to demonstrate the ability of abatacept to improve alone PMR and then to allow a steroid sparing effect after this induction treatment, in early onset PMR.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polymyalgia Rheumatica

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This is a multicenter double blinded randomized placebo controlled trial
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental group
Arm Type
Experimental
Arm Description
Subcutaneous abatacept every weeks during 3 months (W0 to W11). Then, at W12, if PMR-AS>10, they will receive GCs according to the PMR-AS (PMR-AS≤10: no GCs, PMR-AS between 10-20: 10mg/day, PMR-AS between 21-30: GCs at 15mg/d and if PMR-AS> 30: 20mg/d). Dosage of GCs will be decreased between W16 and W24 (1mg every week) in each arm according to PMR-AS (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose). If PMR-AS ≤10, the patients wont receive any treatment until a flare.
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Subcutaneous placebo every week during 3 months (W0 to W11). Then, at week 12, if PMR-AS>10, they will receive GCs according to the PMR-AS (PMR-AS≤10: no GCs, PMR-AS between 10-20: 10mg/day, PMR-AS between 21-30: GCs at 15mg/d and if PMR-AS> 30: 20mg/d). Dosage of GCs will be decreased between W16 and W24 (1mg every week) in each arm according to PMR-AS (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose). If PMR-AS ≤10, the patients won't receive any treatment until a flare.
Intervention Type
Drug
Intervention Name(s)
Abatacept
Intervention Description
Subcutaneous abatacept every weeks during 3 months
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Subcutaneous placebo every week during 3 months
Primary Outcome Measure Information:
Title
Following of one biological parameter (CRP)
Description
The Polymyalgia Rheumatica Activity score is evaluated with a biological parameter named CRP.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Emergence of adverse events (Safety and tolerability)
Description
The safety is evaluated with the adverse events in both arms
Time Frame
36 weeks
Title
Following of the Polymyalgia Rheumatica Activity score
Description
The Polymyalgia Rheumatica Activity score is evalauted with CRP and without CRP. The activity of Polymyalgia Rheumatica is evaluated using the Polymyalgia Rheumatica Activity score (PMR-AS), a disease activity score based on morning stiffness, ability to elevate the upper limbs, physician's global disease assessment and pain assessment measured by the patient using VAS, and the C-reactive protein (CRP) level. The PMR-AS is considered as relevant to define relapse and remission but also to decide if treatment have to be decreased, unchanged or increased (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose)
Time Frame
36 weeks
Title
Medical resource evaluation
Description
The cost of the utilization of Abatacept is evaluated
Time Frame
36 weeks
Title
Following of the cumulative dosages of Glucocorticoids
Description
The cumulative dosages of GCs is evaluated
Time Frame
24 weeks
Title
The flare of the Polymyalgia Rheumatica
Description
The flare of the Polymyalgia Rheumatica will be evaluate by the activity of Polymyalgia Rheumatica which is evaluated using the Polymyalgia Rheumatica Activity score ( (PMR-AS) which is not a scale but a score based on morning stiffness, ability to elevate the upper limbs, physician's global disease assessment and pain assessment measured by the patient using VAS, and the C-reactive protein (CRP) level. The PMR-AS is considered as relevant to define relapse and remission but also to decide if treatment have to be decreased, unchanged or increased (PMR-AS < 10: decrease, PMR-AS > 17 increase to previous dosage, 10 ≤ PMR-AS ≤ 17: stable dose).
Time Frame
36 weeks
Title
Following of the medical exam using the ultrasound Scoring
Description
The ultrasound scoring of synovitis and tenosynovitis is evaluated
Time Frame
12 weeks
Title
Evaluation of FDG uptake using TEP-scanner in RegiOns of Interest
Description
The FDG uptake is evalated with TEP-scanner using the FDG radiotracer
Time Frame
12 weeks
Title
Following the proportion of patients relapse
Description
The proportion of patients relapse or remission is evaluated with the Polymyalgia Rheumatica Activity score>17
Time Frame
36 weeks
Title
Biological markers
Description
The level of biological markers and cell subpopulations with the result of blood test is evaluated. The list of biological markers is (Interleukin, cytokines, immune cells)
Time Frame
36 weeks
Title
Following of the quality of life
Description
The Short Form 36 (SF36) is used to evaluate the quality of life. The SF36 scale includes 36 items divided into 8 dimensions (physical functioning, role limitations related to physical health, physical pain, general health, vitality [energy / fatigue].
Time Frame
36 weeks
Title
Following of the quality of life
Description
The scale EuroQol 5 dimensions (EDQ5) is used to evaluate the quality of life. The EQ-5D scale is a standardised measure of health status to provide a simple, generic measure of health for clinical and economic appraisal, whih is divided by the EQ-5D descriptive system (mobility, self care, usual activities, pain/discomfort, anxiety/depression) and the EQ Visual Analogue scale (EQ VAS). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems).
Time Frame
36 weeks
Title
Following of the quality of life
Description
The Hospital Anxiety and the Depression scale (HAD) is used to evaluate the quality of life. The HAD scale has 14 items rated from 0 to 3 with 7 questions relate to anxiety and 7 others to the depressive dimension.
Time Frame
36 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age older than 50 years Fulfilling ACR/EULAR criteria Disease duration≤6 months No steroid since 2 weeks prior randomization PMR-AS≥ 17 Absence of signs or symptoms of other musculoskeletal or connective tissue conditions Able to give informed consent Concomitant treatments with methotrexate or hydroxychloroquine are not permitted. Exclusion Criteria: Clinical symptoms of giant cell arteritis Uncontrolled high blood pressure or cardiovascular disease Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to PMR Planned surgical procedure or medical history, blood abnormalities or any clinical condition that compromises inclusion History of malignant neoplasm within the last 5 years. Current active infection not controlled Detailed exclusion criteria related to prior or concomitant therapy, general safety and laboratory data are reported in the protocol
Facility Information:
Facility Name
CHRU de Brest
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
CH Le Mans
City
Le Mans
Country
France
Facility Name
CH de Morlaix
City
Morlaix
Country
France
Facility Name
CH St-Malo
City
Saint-Malo
Country
France
Facility Name
CHU Strasbourg
City
Strasbourg
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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Abatacept in earLy Onset Polymyalgia Rheumatica: Study ALORS

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