Clinical trial NCT02778906: Abatacept Reversing Subclinical Inflammation as Measured by MRI in ACPA Positive Arthralgia
Official title: Abatacept Reversing Subclinical Inflammation as Measured by MRI in ACPA Positive Arthralgia (ARIAA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthralgia
Arthritis
Keywords: Abatacept
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2016-05-20
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: RAMRIS synovitis score in the dominant hand 12 and 18 months.
timeFrame: 6,12,18 months
measure: Tenosynovitis score in the dominant hand.
timeFrame: 6,12,18 months
measure: Proportion of patients with new or persistent arthralgia.
timeFrame: 6,12,18 months
measure: Time to disappearance of arthralgia.
timeFrame: 6 months
measure: Proportion of patients with clinical arthritis defined by joint swelling
timeFrame: 6,12,18 months
measure: Proportion of patients with RA (ACR/EULAR 2010 criteria)
timeFrame: 6,12,18 months
measure: Proportion of patients with radiological progress in HR-pQCT analysis comparing baseline image with end of study image.
timeFrame: 18 months
measure: Tender Joint Count 68
timeFrame: 3,6,9,12,15 and 18 months
measure: Disease activity score (DAS) 28
timeFrame: 3,6,9,12,15 and 18 months
measure: Visual analogue scale (VAS) pain
timeFrame: 3,6,9,12,15 and 18 months
measure: Duration of joint stiffness
timeFrame: 3,6,9,12,15 and 18 months
measure: Health assessment Questionnaire (HAQ-DI)
timeFrame: 6,12 and 18 months
measure: Rheumatoid Arthritis Impact of Disease (RAID)
timeFrame: 6,12 and 18 months
measure: Short Form 36 (SF-36)
timeFrame: 6,12 and 18 months
measure: Bone mineral density (BMD)
timeFrame: 18 months
measure: Bone volume per tissue volume (BV/TV)
timeFrame: 18 months
measure: Cortical width in the micro-CT of the distal radius
timeFrame: 18 months
measure: Cortical porosity in the micro-CT of the distal radius
timeFrame: 18 months
measure: RAMRIS erosion score in the dominant hand 12 and 18 months.
timeFrame: 6. 12. 18 months
measure: RAMRIS osteitis score in the dominant hand 12 and 18 months.
timeFrame: 6,12,18 months
measure: Swollen Joint Count 68
timeFrame: 3,6,9,12,15 and 18 months
measure: Visual analogue scale (VAS) patient global
timeFrame: 3,6,9,12,15 and 18 months
measure: Visual analogue scale (VAS) physician global
timeFrame: 3,6,9,12,15 and 18 months
measure: Cortical width in the micro-CT of the metacarpal heads
timeFrame: 18 months
measure: Cortical porosity in the micro-CT of the metacarpal heads
timeFrame: 18 months
Other outcomes:
Locations:
city: Bad Abbach
country: Germany
facility: Klinikum Bad Abbach
city: Berlin
country: Germany
facility: Charite Berlin
city: Berlin
country: Germany
facility: Praxis für Rheumatologie und Innere Medizin
city: Burghausen
country: Germany
facility: Clinic Burghausen
city: Erlangen
country: Germany
facility: University Clinic Erlangen
city: Frankfurt
country: Germany
facility: Centrum für innovative Diagnostik und Therapie (Ciri) Rheumatologie/Immunologie
city: Freiburg
country: Germany
facility: Universitätsklinik Freiburg
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Koeln
country: Germany
facility: Krankenhaus Porz Am Rhein
Study officials:
affiliation: University Clinic Erlangen, Department of Internal Medicine 3, Rheumatology & Immunology
name: Georg Schett, Prof. Dr. univ.
role: PRINCIPAL_INVESTIGATOR
References: