Category: MSA, PSP, CBS: Clinical Trials
Objective: Describe the protocol for a randomized, double-blind phase 3 trial evaluating the efficacy and safety of amlenetug versus placebo in slowing clinical progression in MSA.
Background: Amlenetug (Lu AF82422) is a human monoclonal antibody targeting α-synuclein in clinical development for MSA. Results from a Phase 2 randomized, placebo-controlled trial indicated that treatment with amlenetug was well-tolerated and may slow the clinical progression of MSA, particularly in early disease.
Method: MASCOT (NCT06706622) is a phase 3 clinical trial of two (high- and low-) doses of amlenetug versus placebo (administered by iv infusion every 4 weeks) including a 3-6-week screening period, a double-blind 72-week treatment period, and an optional dose-blinded 72-week open-label extension period. Participants (40-75y) with a diagnosis of clinically probable or established MSA (parkinsonian or cerebellar subtypes), with <5 years from onset of motor symptoms, a Unified MSA Rating Scale (UMSARS) Part I score ≤16 (omitting item 11) at screening and anticipated survival of >3 years are eligible for inclusion.
Results: The primary endpoint is the change from baseline in modified UMSARS score (European and Japanese endpoint is change in UMSARS-total score) at each visit from Baseline up to Week 72, which will be analysed applying a Bayesian progression model. Secondary endpoints include change in UMSARS subscales; Schwab and England Activities of Daily Living (SE-ADL) scores; Global Impressions of Severity as rated by patients (PGI-S), clinicians (CGI-S) and observers (care-partners, OGI-S); time to death; quality of life as rated using the EuroQol 5-dimensions, 5-levels and MSA-QoL questionnaire; and percentage change in brain volume for selected regions of interest. Safety and tolerability will be assessed via adverse event reporting and physical and laboratory tests.
Conclusion: MASCOT will be the first prospective phase 3 trial to evaluate the efficacy and safety of amlenetug versus placebo in MSA. A total of 360 participants will be recruited from sites experienced in the management of people with MSA.
To cite this abstract in AMA style:
L. Kjærsgaard, M. Nørbæk Jørgensen, S. Zanigni, J. Wiedemann, J. Luthman. A Randomized, Double-blind Phase 3 Trial of Amlenetug Versus Placebo in Patients with MSA: The MASCOT Trial [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/a-randomized-double-blind-phase-3-trial-of-amlenetug-versus-placebo-in-patients-with-msa-the-mascot-trial/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-randomized-double-blind-phase-3-trial-of-amlenetug-versus-placebo-in-patients-with-msa-the-mascot-trial/