Based on these evidences, together with our previous finding that itolizumab exhibits the same CD6 recognition profile and a similar affinity constant, but was less immunogenic in monkeys than its murine or GDC-0068 nmr chimeric counterpart [34,35], we expected itolizumab be less immunogenic and toxic than its predecessors, leading to additional benefits in RA patients. The aim of the current study

was to investigate the effect of a 6-week monotherapy with itolizumab in biologic-naïve patients with active moderate to severe RA despite the previous DMARD therapy. The primary intention of the study was to evaluate the safety and tolerability of different doses of itolizumab during 24 weeks. In addition, the study explores preliminary evidences of efficacy. The study was an open-label, non-controlled, dose-finding phase I trial, registered under number RPCEC00000007 at the Cuban Registry of Clinical Trials (www.registroclinico.sld.cu), and conducted at a single clinical center in Havana, Cuba. For trial recruitment active RA patients underwent an eligibility screening between July 2004 and October 2006. After a washout period (at least 4 weeks for DMARDs and glucocorticoids, and 2 weeks for NSAIDs), patients were sequentially enrolled into cohorts of three patients, each receiving a different itolizumab dose (0.2, 04 or 0.8 mg/kg/day), once a week during 6 weeks. The dose range was selected based on in vitro experiments

and from the preceding experiences on clinical trials were performed with the murine ior T1 mAb on RA patients [ 23, 24, [41], [42] and [43]]. Two patients were assigned to 0.1 and 0.6 mg/kg, in two additional Raf inhibitor dose levels that were added during the course of the study. Subjects were followed up for a period of 18 weeks after the

last antibody administration. The 24-weeks study period was divided into 2 stages: week 0–6 was considered the treatment period while from week 7 to week 24 was considered the post-treatment Adenylyl cyclase period (follow up). The study medication was administered intravenously, once a week during 6 weeks. The signs and symptoms were evaluated for 6 months, starting from the first dose administration. Clinical assessments were performed at baseline and at weeks 7, 10 and 24, according to the ACR core set of disease-activity measurements. Safety was monitored during the whole study (weeks 0–24). The restriction for the use of DMARDs, glucocorticoids and NSAIDs was extended from the washout period, including the administration phase and up to 4 weeks after the last itolizumab administration (follow-up, week 10), when these drugs could be administered if disease flares, according to the physician’s criteria. Otherwise, only analgesics were permitted. Patients taking drugs for concomitant disease were required to have been on chronic stable doses prior to screening. Such stable dose had to be maintained throughout the study.