Session Information
Date: Saturday, October 6, 2018
Session Title: Clinical Trials and Therapy in Movement Disorders
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: To assess safety of BIIB092 in participants with progressive supranuclear palsy (PSP) in an OLE of a MAD study.
Background: BIIB092 is a humanized IgG4P monoclonal antibody directed against N-terminal tau fragments in interstitial and cerebrospinal fluid (CSF) being investigated for treatment of tauopathies including PSP. In a randomized, placebo (pbo)-controlled, MAD, phase 1 study in participants with PSP, BIIB092 up to 2100mg was well tolerated and effectively suppressed free extracellular tau in CSF.[1]
Methods: In the MAD study, 48 participants with PSP received BIIB092 (150, 700 or 2100mg) or pbo intravenously every 4 wks (Q4W) for 12 wks in a 3:1 ratio (n=8/panel) and an additional expansion panel received 2100mg (n=18) or pbo (n=6) Q4W for 12 wks [1]; 47 participants enrolled in the ongoing OLE (NCT02658916), continuing with their original BIIB092 panel dose. Safety including adverse events (AEs), serious AEs (SAEs), laboratory tests, electrocardiogram (ECG) and magnetic resonance imaging (MRI) was analyzed by original dose panel from OLE entry to data cutoff (17 Nov 2017; data preliminary after Aug 2017).
Results: By data cutoff, 12 (25.5%) participants had discontinued: consent withdrawal (n=5), AEs (n=3), PSP progression (n=2), and other (n=2). OLE BIIB092 exposure was 48 wks among ongoing participants. Adverse events occurred in 42/47 participants including 8/8, 8/8 and 26/31 in the 150, 700 and 2100mg groups. Treatment-related AEs occurred in 3 (37.5%) of 150 and 700mg participants each and 5 (16.1%) of 2100mg participants. The most common AE was fall (61.7%). All SAEs were deemed nontreatment-related by investigators (10 SAEs in 8 participants) and included 12.5%, 37.5% and 12.9% in the 150, 700 and 2100mg groups. Three participants had SAEs that led to withdrawal: metabolic encephalopathy and aspiration pneumonia (n=1, 150mg); respiratory arrest (n=1, 2100mg) and aspiration pneumonia (n=1, 2100mg); the latter 2 SAEs resulted in death. One participant died from PSP progression. No treatment-related trends or clinically significant abnormalities in vital signs, MRI or ECG were identified, except for 1 participant with treatment-related elevation in creatine kinase.
Conclusions: In this safety interim analysis, no dose-related safety trends were seen. Treatment with OLE BIIB092, up to 2100mg Q4W, appeared to be safe and well tolerated in participants with PSP.
References: 1. Qureshi I, Grundman M, Tirucherai GS, et al. Multiple ascending dose study of the tau-directed monoclonal antibody BIIB092 in patients with progressive supranuclear palsy. Poster presented at 10th Clinical Trials on Alzheimer’s Disease (CTAD). November 1–4,2017. Poster LBP32.
To cite this abstract in AMA style:
T. Dam, L. Zhang, I. Qureshi, M. Grundman, G. Tirucherai, C. Bechtold, M. Ahlijanian, L. Golbe, L. Honig, S. Isaacson, M. Grossman, N. McFarland, I. Litvan, D. Geldmacher, T. Xie, Y. Bordelon, P. Tuite, P. O’Suilleabhain, T. Zesiewicz, B. Han, A. Boxer. Open-label extension (OLE) of a multiple ascending dose (MAD) study of BIIB092 in participants with PSP: Safety analysis [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/open-label-extension-ole-of-a-multiple-ascending-dose-mad-study-of-biib092-in-participants-with-psp-safety-analysis/. Accessed June 15, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/open-label-extension-ole-of-a-multiple-ascending-dose-mad-study-of-biib092-in-participants-with-psp-safety-analysis/