Abatacept to Silence anti-Citrullinated protein Antibody-expressing B cells in Rheumatoid Arthritis

Phase 1

Conditions: Patients with early, methotrexate-naïve, ACPA-positive rheumatoid arthritis
MedDRA version: 20.0Level: LLTClassification code 10003268Term: Arthritis rheumatoidSystem Organ Class: 100000018818
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2017-002878-38-NL

Lead Sponsor: eiden University Medical Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 46

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria. Each patient must:
-have a diagnosis of rheumatoid arthritis according to the revised 2010 EULAR/ACR criteria for classification of RA
-have a positive test for the presence of anti-citrullinated protein antibodies (ACPA) in serum as determined by routine clinical assay.
-have adequate hematologic function (ANC = 4000 cells/µL, platelet count = 150000/µL, and hemoglobin = 10 g/dL (corresponding to 6.2 mmol/L)
-have serum creatinine concentrations < 1.5 mg/dl and/or a normal creatinine clearance
-be at least 18 years of age
-if a female patient is of childbearing potential, agree to: comply with effective contraceptive measures, use adequate contraception since the last menses, use adequate contraception during the study, have a negative pregnancy test within one week of study entry
-be willing to receive a booster vaccination against tetanus toxoid three to four weeks prior to randomization
-be able and willing to give written informed consent prior to entry in the study

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study. Any patient who has:
-been previously treated with either abatacept and/or methotrexate or another csDMARD
-been previously treated with a kinase inhibitor
-been previously treated with rituximab or another B-cell depleting agent
-been previously treated with a biological DMARD
-received intra-articular or systemic glucocorticoid injections or has required treatment for acute RA flare (not being part of a regular therapeutic regimen) within four weeks prior to randomization or requires narcotic analgesics other than those accepted by the investigator for analgesia (e.g. paracetamol, codeine, tramadol)
-been tested negative for anti citrullinated protein antibodies
-contraindications for a booster vaccination against tetanus toxoid prior to randomization to the treatment arms; if a patient refuses booster vaccination but has detectable numbers of tetanus toxoid-specific B cells circulating in peripheral blood prior to the baseline visit, the patient can still be allowed to participate in the study at the judgement of the investigator.
-evidence of any other major chronic inflammatory disease (i.e. psoriasis, psoriatic arthritis, spondyloarthritis or inflammatory bowel disease)
-evidence of poorly controlled diabetes, history of clinically significant pulmonary disease including interstitial lung disease or methotrexate-induced lung disease, poorly controlled asthma or a history of severe life-threatening asthma attacks, history of active tuberculosis, history of latent tuberculosis without adequate medical treatment, liver cirrhosis or fibrosis, significant active infection or any underlying diseases that could predispose the subject to infections
-liver function abnormality (total bilirubin = 1.5 x the upper limit of normal range, AST, ALT = 3 x upper limit of normal range)
-concurrent treatment with an experimental drug or who has participated in another clinical trial with an investigational drug within 30 days prior to study entry
-pre-existing sensory or motor polyneuropathy = Grade 2 according to NCI CTC
-past or current history of neoplasms, except for curatively treated non-melanoma skin cancer, adequately treated in situ carcinoma of the cervix or another cancer curatively treated and with no evidence of disease for at least 10 years
-significant cardiac disease, cardiac arrhythmia (Lown Grade = III), uncontrolled hypertension or recent history of myocardial ischemia
-Pregnant or nursing women