A clinical exploratory study with itolizumab, an anti-CD6 monoclonal antibody, in patients with rheumatoid arthritis

Abstract

T cells are involved in the pathogenesis of rheumatoid arthritis (RA). CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes, that has been linked to autoreactive responses. The purpose of this study was to evaluate the safety, immunogenicity and preliminary efficacy of itolizumab, a humanized anti-CD6 monoclonal antibody, in patients with active rheumatoid arthritis. Fifteen patients were enrolled in a phase I, open-label, dose-finding study. Five cohorts of patients received a weekly antibody monotherapy with a dose-range from 0.1 to 0.8 mg/kg. Itolizumab showed a good safety profile, with no severe or serious adverse events reported so far. No signs or symptoms associated with immunosuppression were observed in the study. Objective clinical responses were achieved in more than 80% of patients after treatment completion, and these responses tend to be sustained afterwards. This clinical study constitutes the first evidence of the safety and positive clinical effect of a monotherapy using an anti-CD6 antibody in patients with rheumatoid arthritis.

Keywords: ACR, American College of Rheumatology; AE, adverse events; CD6; CRP, C reactive protein; DMARD, disease-modifying antirheumatic drug; ESR, eritrosedimentation rate; Exploratory study; NSAIDs, nonsteroidal antiinflammatory drugs; RA, rheumatoid arthritis; RF, rheumatoid factor; Rheumatoid arthritis; SAE, serious adverse event.; T lymphocyte; iv, intravenous; mAbs, monoclonal antibodies.

Fig. 1

Scatter of individual values for total white blood cells (WBC) (A) and absolute lymphocyte count (ALC) (B) for individual subjects of overall study cohort (safety population) over time. LLN: lower limit of normal; ULN: upper limit of normal. The graph also shows the normal laboratory reference ranges and the clinically significant range as per CTCAE v 3 Grade 1.

Fig. 2

Anti-idiotypic IgG response during T1h mAb therapy. The immunogenicity of the humanized T1h mAb was monitored prior to dosing and weekly until the week 10 after first administration. The IgG anti-idiotypic response of treated patients against the mouse variable region of the humanized mAb T1h was evaluated using an ELISA system coated with the anti- CD6 mAb iort1. Positive response was considered when the ratio post-treatment OD/ pre- treatment OD was >2 for each patient.

Fig. 3

Change in hemoglobin with T1h treatment during the study. LLN: lower limit of normal.