Abatacept Reversing Subclinical Inflammation as Measured by MRI in ACPA Positive Arthralgia

Study Overview
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Brief Summary
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This is a randomised double-blinded placebo-controlled multi centre study in 98 patients with ACPA positive arthralgia. The study is composed of 2 arms with a 1:1 randomisation at baseline: Treatment phase will be 6 months. Group 1: Abatacept s.c. 125 mg weekly for 6 months vs. Group 2: Placebo s.c. for 6 months. After 6 months both groups will run into the follow up period for another 12 months up to month 18. Patients developing arthritis will be treated according to local guidelines.

Official Title
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Abatacept Reversing Subclinical Inflammation as Measured by MRI in ACPA Positive Arthralgia (ARIAA)

Conditions
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Arthralgia, Arthritis

Intervention / Treatment
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* Drug: Abatacept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females and males aged ≥ 18 years at time of consent ACPA (with or without RF) Joint pain (hand, feet, knee, shoulder or elbow) present for at least 6 weeks prior to inclusion or in past history Presence of synovitis (synovialitis or tenosynovitis) or osteitis in MRI of the dominant hand at baseline Women of childbearing potential or men capable of fathering children must be using effective contraception during treatment with abatacept and up to 14 weeks after the last dose of abatacept treatment. Must understand and voluntarily sign an informed consent form including written consent for data protection Must be able to adhere to the study visit schedule and other protocol requirements Exclusion Criteria: Presence of arthritis in hand, feet, knee, shoulder or elbow joints defined as swelling Current treatment with glucocorticoids conventional or biologic DMARDs Previous treatment with abatacept Investigational study drug within 4 weeks (or 5 half lives, whichever is longer) prior to randomization Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study Any other autoimmune or inflammatory disease such as SLE, PSS, MCTD, SpA, Behcet disease, vasculitis or autoimmune hepatitis. Any malignancy in the last 5 years Chronic infection such as latent TB (TB not adequately treated according to guidelines) or hepatitis B or C infection Immunocompromised or HIV-positive patients Uncontrolled severe concomitant disease Patients who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG). Pregnant or lactating females Patients who possibly are dependent on the Principal Investigator or Investigator (e.g. family members).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Abatacept<br>Abatacept 125 mg s.c. weekly | Drug: Abatacept<br>* Administration of Abatacept s.c. 125mg/weekly according to the Label for Rheumatoid arthritis<br>* Other names: Orencia;|
| Placebo Comparator: Placebo<br>Placebo (NaCl 0,9%) s.c. weekly | Drug: Placebo<br>* Administration of the comparator s.c. weekly in comparable to verum<br>* Other names: Comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with an improvement of acute inflammation characterised as improvement of synovitis (synovialitis or tenosynovitis) or osteitis in the MRI of the dominant hand after 6 months of treatment with abatacept or placebo |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RAMRIS synovitis score in the dominant hand 12 and 18 months. |  | 6,12,18 months | 
| Tenosynovitis score in the dominant hand. |  | 6,12,18 months | 
| Proportion of patients with new or persistent arthralgia. |  | 6,12,18 months | 
| Time to disappearance of arthralgia. |  | 6 months | 
| Proportion of patients with clinical arthritis defined by joint swelling |  | 6,12,18 months | 
| Proportion of patients with RA (ACR/EULAR 2010 criteria) |  | 6,12,18 months | 
| Proportion of patients with radiological progress in HR-pQCT analysis comparing baseline image with end of study image. |  | 18 months | 
| Tender Joint Count 68 |  | 3,6,9,12,15 and 18 months | 
| Disease activity score (DAS) 28 |  | 3,6,9,12,15 and 18 months | 
| Visual analogue scale (VAS) pain |  | 3,6,9,12,15 and 18 months | 
| Duration of joint stiffness |  | 3,6,9,12,15 and 18 months | 
| Health assessment Questionnaire (HAQ-DI) |  | 6,12 and 18 months | 
| Rheumatoid Arthritis Impact of Disease (RAID) |  | 6,12 and 18 months | 
| Short Form 36 (SF-36) |  | 6,12 and 18 months | 
| Bone mineral density (BMD) |  | 18 months | 
| Bone volume per tissue volume (BV/TV) |  | 18 months | 
| Cortical width in the micro-CT of the distal radius |  | 18 months | 
| Cortical porosity in the micro-CT of the distal radius |  | 18 months | 
| RAMRIS erosion score in the dominant hand 12 and 18 months. |  | 6. 12. 18 months | 
| RAMRIS osteitis score in the dominant hand 12 and 18 months. |  | 6,12,18 months | 
| Swollen Joint Count 68 |  | 3,6,9,12,15 and 18 months | 
| Visual analogue scale (VAS) patient global |  | 3,6,9,12,15 and 18 months | 
| Visual analogue scale (VAS) physician global |  | 3,6,9,12,15 and 18 months | 
| Cortical width in the micro-CT of the metacarpal heads |  | 18 months | 
| Cortical porosity in the micro-CT of the metacarpal heads |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Abatacept