First-in-Human Study of RLYB116 in Healthy Participants

RLYB116 is being developed for administration for the treatment of complement mediated diseases. RLYB116 is a small protein composed of an Affibody® Z-domain that binds with high affinity to C5, inhibiting terminal complement activation, and an albumin binding domain (ABD) that extends the effective plasma half-life of the protein by targeting serum albumin. The study consists of two parts: Part A (Single Ascending Dose): The participant will be randomized in 3:1. The total of 5 ascending dose cohorts are planned to be dosed in a sequential manner in Part A of the study. Total of 8 participants will be enrolled in each dose level and the 6 participants will receive RLYB116 per dose level and 2 participants will receive matching placebo in each dose level. Dose level 1: 2mg administered subcutaneously once on Day 1 Dose level 2: 10 mg administered subcutaneously once on Day 1 Dose level 3: 30 mg administered subcutaneously once on Day 1 Dose level 4: 100 mg administered subcutaneously once on Day 1 Dose level 5: 300 mg administered subcutaneously once on Day 1 Each cohort will be administered to a distinct group of subjects and escalation to the next higher dose level will occur only after completion of a review of clinical safety and available pharmacokinetic data by the Safety Review Committee. Part B (Multiple Ascending Dose): The participant will be randomized 5:1. Four cohorts will be executed sequentially. Total of 12 participants will be enrolled in each dose level and the 10 participants will receive RLYB116 per dose level and 2 participants will receive matching placebo in each dose level. The multiple dose phase may initiate after the Safety Review Committee review of the safety data from the fifth cohort of the single dose phase and agreement on the study proceeding.  Dose level 1 (B1): 100 mg administered subcutaneously once on Day 1, Day 8, Day 15, Day 22, Day 29 Dose level 2 (B4):  100 mg administered subcutaneously once on Day 1, Day 3, Day 5, Day 8, Day 15, Day 22, Day 29 Dose level 3 (B2):  Less than or equal to 150mg administered subcutaneously once on Day 1, Day 8, Day 15, Day 22, Day 29 Dose level 4 (B7):  Less than or equal to 125 mg administered subcutaneously once on Day 1, Day 4, Day 8, Day 11, Day 15, Day 18, Day 22, Day 25, Day 29 The planned multiple dose cohorts may be adjusted for the dose selected or the number of cohorts based on emergent safety, tolerability, pharmacokinetic, or pharmacodynamic data from the study for both the part A and B. In both the Part A and Part B, the RLYB116 will be administered in the unit at the specified times under supervision by principal investigator and intervention adherence will be monitored by study staff.