Lu AF82422 for Multiple System Atrophy

(MASCOT Trial)

Recruiting at 16 trial locations

Overseen By Email contact via H. Lundbeck A/S

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: H. Lundbeck A/S

Disqualifiers: Previous Lu AF82422, Other CNS diseases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 36

360 Participants Needed

Trial Summary

What is the purpose of this trial?

The main goal of this trial is to evaluate the efficacy and safety of Lu AF82422 for the treatment of participants with Multiple System Atrophy (MSA).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that you should not have taken any investigational medicinal product within 3 months or 5 half-lives of that product before starting the trial. It's best to discuss your current medications with the trial team.

How is the drug Lu AF82422 different from other treatments for multiple system atrophy?

Lu AF82422 is unique because it targets alpha-synuclein aggregates, which are abnormal protein clumps found in the brains of people with multiple system atrophy, whereas current treatments mainly focus on managing symptoms rather than addressing the underlying disease process. ^{1 2 3 4 5}

Research Team

Email contact via H. Lundbeck A/S

Principal Investigator

H. Lundbeck A/S

Eligibility Criteria

This trial is for individuals with Multiple System Atrophy (MSA), either parkinsonian type (MSA-P) or cerebellar type (MSA-C). Participants must have been diagnosed within the last 5 years and are expected to live more than 3 years. They should be able to receive medication intravenously and have a certain level of disease severity as measured by a specific scale.

Inclusion Criteria

My motor symptoms started less than 5 years ago.

I have been diagnosed with MSA-P or MSA-C according to the 2022 MDS criteria.

* The participant has an anticipated survival of \>3 years, in the opinion of the investigator, at the Screening Visit.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3-6 weeks

Placebo-controlled Period (PCP)

Participants are randomized to receive either Lu AF82422 high dose, Lu AF82422 low dose, or placebo. Intravenous infusions are administered approximately every 4 weeks.

72 weeks

18 visits (in-person)

Open-label Extension (OLE)

Participants may opt into an open-label extension where all receive Lu AF82422. Intravenous infusions are administered approximately every 4 weeks.

72 weeks

18 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lu AF82422

Trial Overview The trial is testing Lu AF82422, which is being compared against a placebo to assess its effectiveness and safety in treating MSA. The main goal is to see if this new treatment can help manage symptoms better than no treatment at all.

Participant Groups

Group I: Lu AF82422 Low Dose Experimental Treatment 1 Intervention

Participants will receive Lu AF82422 by intravenous infusion

Group II: Lu AF82422 High Dose Experimental Treatment 1 Intervention

Participants will receive Lu AF82422 by intravenous infusion

Group III: Placebo Placebo Group 1 Intervention

Participants will receive commercially available saline solution for infusion

Lu AF82422 is already approved in United States, European Union, Japan, China for the following indications:

Approved in United States as Lu AF82422 for:

• None approved yet; in Phase III trials for Multiple System Atrophy

Approved in European Union as Lu AF82422 for:

• None approved yet; granted Orphan Drug Designation for Multiple System Atrophy

Approved in Japan as Lu AF82422 for:

• None approved yet; in Phase III trials for Multiple System Atrophy

Approved in China as Lu AF82422 for:

• None approved yet; in Phase I trials for Multiple System Atrophy

Who Is Running the Clinical Trial?

H. Lundbeck A/S

Lead Sponsor

Trials

332

Recruited

78,300+

Charl van Zyl

H. Lundbeck A/S

Chief Executive Officer since 2023

Degree in Medical Biochemistry from the University of Cape Town, South Africa

Johan Luthman

H. Lundbeck A/S

Chief Medical Officer since 2019

MD from the University of Gothenburg, Sweden

Findings from Research

Multiple system atrophy (MSA) is a severe neurodegenerative disorder with a mean survival of only 9 years, characterized by autonomic failure and either parkinsonism or cerebellar ataxia, with limited treatment options available.

While pharmacological treatments for motor symptoms are largely ineffective, early identification and treatment of autonomic and urogenital symptoms can be beneficial, and ongoing multicenter trials are exploring potential neuroprotective therapies like riluzole and human recombinant growth hormone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple system atrophy: an update. Wenning, GK., Geser, F., Stampfer-Kountchev, M., et al.[2013]

An international meeting in 2014 brought together experts to identify key research areas for improving understanding and treatment of multiple system atrophy (MSA), a rare neurodegenerative disorder.

Eight critical topics were established, including pathogenesis, clinical measures, and treatment designs, with expert-led working groups creating prioritized recommendations to guide future research efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting. Walsh, RR., Krismer, F., Galpern, WR., et al.[2021]

In a study involving 18 patients with multiple system atrophy (MSA), 8 patients with Parkinson's disease (PD), and 10 healthy volunteers, it was found that MSA patients activated different brain regions compared to PD patients, particularly showing less activation in the cerebellum and more in the supplementary motor and superior parietal areas.

After an acute levodopa challenge, MSA patients showed reduced activation in the anterior cingulate, while PD patients increased activation in the right cerebellum, indicating that MSA patients do not benefit from levodopa in the same way as PD patients due to underlying cerebellar dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor activation in multiple system atrophy and Parkinson disease: a PET study. Payoux, P., Brefel-Courbon, C., Ory-Magne, F., et al.[2016]

In a placebo-controlled trial involving 10 patients with probable multiple system atrophy (MSA), riluzole (100 mg twice daily) was found to be well tolerated but did not show significant anti-Parkinsonian effects based on the Unified Parkinson's Disease Rating Scale (UPDRS).

The results suggest that riluzole is unlikely to provide clinically meaningful benefits for Parkinsonian symptoms in MSA, prompting further investigation into its potential disease-modifying effects in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of riluzole in multiple system atrophy. Seppi, K., Peralta, C., Diem-Zangerl, A., et al.[2015]

In a study of 139 patients suspected of having multiple system atrophy (MSA), [123I]Ioflupane SPECT demonstrated high sensitivity (82.46%) and positive predictive value (86.24%), making it a reliable diagnostic tool for MSA, especially effective in identifying the parkinsonian subtype (MSA-P) with a sensitivity of 97.26%.

The SPECT imaging was significantly more effective than MRI, which was normal in 89.2% of cases, highlighting its utility in distinguishing between healthy individuals and those with MSA, as well as differentiating between the MSA-P and MSA-C subtypes at the initial clinical suspicion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Effectiveness of [123I]Ioflupane Single Photon Emission Computed Tomography (SPECT) in Multiple System Atrophy. Villena-Salinas, J., Ortega-Lozano, SJ., Amrani-Raissouni, T., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Multiple system atrophy: an update. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Recommendations of the Global Multiple System Atrophy Research Roadmap Meeting. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Motor activation in multiple system atrophy and Parkinson disease: a PET study. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of riluzole in multiple system atrophy. [2015]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Diagnostic Effectiveness of [123I]Ioflupane Single Photon Emission Computed Tomography (SPECT) in Multiple System Atrophy. [2023]