[O2–17–01]: RESULTS OF A PHASE 1, SINGLE ASCENDING DOSE, PLACEBO‐CONTROLLED STUDY OF ABBV‐8E12 IN PATIENTS WITH PROGRESSIVE SUPRANUCLEAR PALSY AND PHASE 2 STUDY DESIGN IN EARLY ALZHEIMER's DISEASE

Abstract

ABBV-8E12 is a humanized anti-tau monoclonal antibody being developed for the treatment of PSP and Alzheimer's disease (AD). The results of a phase 1 study of ABBV-8E12 in subjects with Progressive Supranuclear Palsy (PSP) and design of a phase 2 study assessing efficacy, safety, and tolerability of ABBV-8E12 in subjects with AD will be presented. The phase 1 study was a double-blind, placebo-controlled, single ascending dose study assessing the safety, tolerability, and pharmacokinetics of ABBV-8E12 in subjects with PSP (NCT02494024). Subjects were randomized 3:1 to either drug or placebo in 4-subject blocks and received a single intravenous dose of ABBV-8E12 (2.5, 7.5, 15, 25, or 50 mg/kg) or placebo. Safety and pharmacokinetics were monitored for 84 days post-dosing. Thirty subjects were enrolled and randomized. At screening, the mean (SD) subject age was 69.4 years (7.4); 16 (53%) were male, and the mean (SD) PSP Rating Scale score was 35.6 (7.6). Twenty-seven subjects completed the 84-day follow-up and 1 (3.3%) subject withdrew from the study due to adverse event (AE). AEs occurred in 21 of the 30 (70%) subjects. The AEs with the highest subject incidence were dermatitis (n=5) and fall (n=5) (Table 1). Three serious AEs were reported (10% incidence), one in each of the 15, 25, and 50 mg/kg cohorts. Noncompartmental analysis based on the complete pharmacokinetic dataset indicates dose-proportional increases in AUC and Cmax. The estimated half-life of ABBV-8E12 is approximately 1 month. A phase 2 study evaluating ABBV-8E12 in early AD subjects is currently recruiting (NCT02880956) (Figure 1). Eligible subjects (n=400) will meet criteria for early AD and have a positive amyloid Positron Emission Tomography scan. In addition to the ongoing phase 2 study in AD subjects, a phase 2 study evaluating the 52-week efficacy and safety of ABBV-8E12 in PSP subjects (n=180) is also currently recruiting (NCT02985879). When administered as a single dose up to 50 mg/kg in PSP subjects, ABBV-8E12 exhibited an acceptable safety and tolerability profile to support repeat-dose testing in subjects with tauopathies. Phase 2 study design. Design of a phase 2, randomized, double-blind, placebo-controlled multiple dose study to assess the efficacy and safety of ABBV-8E12 in early Alzheimer's disease (NCT02985879).