Study Design of TAK-341-2001: A Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-341 in Subjects With Multiple System Atrophy
Jaya Padmanabhan1, Elena Ratti1, Polyna Khudyakov1, Wei Yin1, Stephen Zicha1, Olga Golonzhka1, Tairmae Kangarloo1, Brian Harel1, Nancy Goodman1, Emmanuelle Magueur1, Craig Shering2, Thor Ostenfeld2, Antonio Laurenza1, Arthur Simen1
1Takeda Development Center Americas Inc., 2AstraZeneca
Objective:
To describe the design of a clinical trial that will evaluate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of intravenously administered TAK-341 in participants with multiple system atrophy (MSA).
Background:
MSA is a rapidly progressing and fatal neurological disorder, with no treatments that can slow its progression. TAK-341 (MEDI1341) is a monoclonal antibody that binds to the C-terminal region of human alpha-synuclein. In a mouse model, TAK-341 attenuated cell-to-cell spreading of alpha-synuclein pathology in the brain. Single ascending dose (NCT03272165) and multiple ascending dose (NCT04449484) studies in healthy participants and participants with Parkinson disease, respectively, have recently completed and support continued development of TAK-341.
Design/Methods:
This randomized, double-blind, placebo-controlled, Ph2 study (NCT05526391) will enroll approximately 138 participants globally who are ≥40 years of age, with probable or possible MSA according to modified Gilman 2008 criteria. Participants’ onset of MSA symptoms must have occurred ≤4 years before screening as demonstrated by MSA symptoms measured with the Unified MSA Rating Scale (UMSARS).
Participants will receive 13 intravenous infusions of either TAK-341 or placebo, approximately every 4 weeks. The study comprises a ≤42-day screening period, a 52-week double-blind treatment period, and a follow-up safety visit.
The study’s primary objective is to evaluate the efficacy of TAK-341 versus placebo, as measured by the change from baseline after 52 weeks on a modified UMSARS Part I. Secondary objectives are to evaluate the efficacy of TAK-341 versus placebo, as measured by change from baseline after 52 weeks on the following: UMSARS Part I, Part II, and total scores, an 11-item selection of UMSARS Part I and II items, CGI-S, SCOPA-AUT, and overall survival. Secondary objectives also include evaluation of pharmacokinetic parameters. Safety endpoints will also be evaluated.
Conclusions:
Trial results will yield insight into the role of alpha-synuclein in MSA disease progression, and further inform TAK-341’s risk-benefit profile.