Clinical trial NCT03632187: Abatacept in earLy Onset Polymyalgia Rheumatica: Study 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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Polymyalgia Rheumatica
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-08-15
Enrollment: 34
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicenter double blinded randomized placebo controlled trial
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Following of one biological parameter (CRP)
timeFrame: 12 weeks
Secondary outcomes:
measure: Emergence of adverse events (Safety and tolerability)
timeFrame: 36 weeks
measure: Following of the Polymyalgia Rheumatica Activity score
timeFrame: 36 weeks
measure: Medical resource evaluation
timeFrame: 36 weeks
measure: Following of the cumulative dosages of Glucocorticoids
timeFrame: 24 weeks
measure: The flare of the Polymyalgia Rheumatica
timeFrame: 36 weeks
measure: Following of the medical exam using the ultrasound Scoring
timeFrame: 12 weeks
measure: Evaluation of FDG uptake using TEP-scanner in RegiOns of Interest
timeFrame: 12 weeks
measure: Following the proportion of patients relapse
timeFrame: 36 weeks
measure: Biological markers
timeFrame: 36 weeks
measure: Following of the quality of life
timeFrame: 36 weeks
measure: Following of the quality of life
timeFrame: 36 weeks
measure: Following of the quality of life
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Brest
country: France
facility: CHRU de Brest
city: Le Mans
country: France
facility: CH Le Mans
city: Morlaix
country: France
facility: CH de Morlaix
city: Saint-Malo
country: France
facility: CH St-Malo
city: Strasbourg
country: France
facility: CHU Strasbourg
Study officials:
References: