HLA typing was performed by DNA sequence-based methodology (Abbott Molecular, Abbott Park, IL) using buccal swabs obtained from subjects prior to dosing on day 1. The following exons were routinely sequenced: HLA-A, B, C: Exons 2, 3, selleckchem 4; HLA-DRB1: Exon 2; HLA-DQB1: Exons 2, 3. Remaining ambiguities were resolved by application of “heterozygosity ambiguity resolution primers” (Abbott) or by PCR-SSP (Life Technologies, Carlsbad, CA). No formal analysis was performed to determine sample size or to assess safety data. The IFN-γ
ELISpot and LPA algorithms and response criteria together with ASCA response criteria were predefined. All randomized subjects who received at least one dose of study treatment were included in the safety analysis. Sixty subjects were randomized of whom 57 completed the study (Fig. 1). Three subjects were discontinued because of an adverse event (n = 1) and protocol violation (n = 2). Demographic and baseline subject characteristics were similar for Cohorts A and B ( Table 1). Thirty-nine (65%) subjects reported adverse events (Table 2); all were graded mild or moderate and none was Selleck Quizartinib serious. A full listing of moderate adverse
events is shown in Supplementary Table 5. One subject who received monthly injections of 80 YU GS-4774 was discontinued due to mild paresthesia, which resolved and was judged by the Investigator to be related to study treatment. The number of individual adverse events increased with dose and more adverse events were reported following weekly than monthly dosing. Most adverse events reported were judged related to study treatment by the Investigator; all of these were injection-site reactions except for one transient episode of headache in the 40 YU group and another of myalgia in the 80 YU
dose group. Adverse events experienced by more than one subject in a single cohort are shown in Supplementary Table 6. The most frequent adverse events were injection-site reactions, Mephenoxalone reported by 23 (38%) subjects (Table 2). Injection-site reactions were reported more frequently after weekly (n = 15 subjects) than monthly dosing (n = 8). All reactions resolved and were mild with the exception of two episodes of moderate injection-site pain reported by one subject in Cohort A 80 YU. Both episodes resolved without treatment and were judged to be related to study treatment. Two of the mild injection-site reactions (induration and pain) required treatment (acetaminophen and ice). Four patients had Grade 3 decreases in hemoglobin (two in Cohort A 10 YU, one in Cohort B 40 YU, and one in Cohort B 80 YU). There were no other Grade ≥2 laboratory abnormalities. Only two laboratory abnormalities were reported as adverse events: decrease in absolute neutrophils and white blood cell counts by one subject in Cohort A 40 YU. Both events were mild and considered not related to study treatment. No clinically relevant changes were reported for vital signs or ECG.