Study treatment
death, anaphylactic reaction, illness
ANAPHYLACTIC REACTION
Study patients were randomly allocated in a 3:1 ratio to receive IMCY-0098 or placebo. Treatment allocation at each site was performed using central randomization via an Interactive Web Response System.Treatment was injected subcutaneously in the upper arm (midway between the elbow and the shoulder); each dose was divided into two halves, which were administered concomitantly into both arms. Treatment was injected in both arms in order to stimulate the immune system via two draining lymph nodes and, consequently, to maximize the treatment-related immune response. Treatment was administered in four doses, given in 2-week intervals, with aluminum hydroxide adjuvant (alum) at a concentration of 500 μg/mL.Patients allocated to receive IMCY-0098 were sequentially enrolled to receive dose A (first administration 50 μg, followed by 3 × 25 μg), dose B (first administration 150 μg, followed by 3 × 75 μg) or dose C (first administration 450 μg, followed by 3 × 225 μg). In each cohort, the first four patients stayed in the hospital for a 24-h safety follow-up after each administration, and an interval of 2 days was observed between these four patients and other patients enrolled to receive the same dose. Patients allocated to receive placebo received matching volumes of placebo solution to maintain blinding.Interim safety evaluations were conducted by an independent Data and Safety Monitoring Board to allow inclusion of patients into the next cohort. Evaluations were conducted after four patients received their first administration and ≥ 3 patients received all four administrations of dose A (to allow inclusion of patients for dose B), and after four patients received their first administration and ≥ 3 patients received all four administrations of dose B (to allow inclusion of patients for dose C).Data were collected in a double-blind manner until all patients completed the study to Week 24 or were prematurely withdrawn from the study. Patients could be withdrawn from the study due to an AE, development of illness, pregnancy, or loss to follow-up. If a patient’s body temperature was > 37.5 °C, injection of study treatment was to be postponed until the temperature was < 37.1 °C. Study treatment was to be discontinued in case of an anaphylactic reaction to administration, any AE Grade > 2 as defined by U.S. Department of Health and Human Services (grade 1 – mild; grade 2 – moderate; grade 3 – severe or medically significant; grade 4 – life-threatening; grade 5 – death related to AE) [