Lu AF82422 for Multiple System Atrophy

(MASCOT Trial)

Recruiting at 81 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Lu AF82422 to determine its effectiveness and safety for people with Multiple System Atrophy (MSA), a condition that causes movement and balance problems. Participants will receive either a low dose, a high dose of Lu AF82422, or a placebo (inactive treatment) through an IV. Those diagnosed with MSA who began experiencing motor symptoms within the last 5 years might be a good fit for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment nearing widespread availability.

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.

Is there any evidence suggesting that Lu AF82422 is likely to be safe for humans?

Research has shown that Lu AF82422 has been safe in earlier studies. Patients who took Lu AF82422 found it well-tolerated, with no major safety issues. In one study, patients received different doses to observe their reactions, and the results were positive, indicating that participants generally handled the treatment well.

Lu AF82422 is a human monoclonal antibody designed to target specific proteins in the body. Specifically, it targets a protein linked to multiple system atrophy (MSA). This treatment has been carefully developed to minimize risks to patients.

Overall, existing research supports that Lu AF82422 is safe for humans, with manageable side effects. As it progresses through clinical trials, researchers closely monitor its safety to ensure it is a viable option for people with MSA. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Lu AF82422 is unique because it targets alpha-synuclein, a protein believed to play a key role in the progression of Multiple System Atrophy (MSA). Unlike current treatments that mainly focus on managing symptoms, such as blood pressure medications or drugs to reduce tremors, Lu AF82422 aims to address the underlying disease process. This monoclonal antibody is administered through intravenous infusion and has the potential to slow or even halt disease progression, offering a new hope for patients with MSA. Researchers are excited about its potential to not only improve symptoms but also have a lasting impact on the disease itself.

What evidence suggests that Lu AF82422 might be an effective treatment for Multiple System Atrophy?

Research has shown that Lu AF82422 may help treat Multiple System Atrophy (MSA). In earlier studies, this treatment was generally safe and appeared more effective for patients with milder MSA symptoms. This trial will test Lu AF82422 at both low and high doses, targeting a protein called alpha-synuclein, which is linked to MSA and may help slow or alter the disease's progression. While it looks promising, researchers continue to study its effectiveness through ongoing clinical trials. ^{5 6 7 8 9}

Who Is on the Research Team?

Email contact via H. Lundbeck A/S

Principal Investigator

H. Lundbeck A/S

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Amlenetug Low Dose Experimental Treatment 1 Intervention

Participants will receive amlenetug by intravenous infusion

Group II: Amlenetug High Dose Experimental Treatment 1 Intervention

Participants will receive amlenetug 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

Published Research Related to This Trial

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]

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 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]

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]

Citations

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clinicaltrials.gov

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NCT06706622 | A Trial of Lu AF82422 in Participants With ...

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).

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A-Synuclein Antibody Lu AF82422 Shows Disease ...

Lu AF84222 was considered well tolerated, with greater treatment effects observed in a subgroup of patients with less impaired multiple system atrophy.

3.

firstwordpharma.com

firstwordpharma.com/story/5823432

Lundbeck announces supportive phase II results with Lu ...

A total of N=61 MSA patients were randomized 2:1 to either Lu AF82422 or placebo and treated between 48 to 72 weeks, followed by an ongoing 48 ...

4.

movementdisorders.onlinelibrary.wiley.com

movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29784

Randomized Phase I Trial of the α‐Synuclein Antibody Lu ...

Overall, single intravenous infusions of Lu AF82422 were safe and well tolerated, and no serious adverse events (AE) were observed; the most ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11055738/

Multiple system atrophy: an update and emerging directions of ...

Lundbeck has recently advanced the development of Lu AF82422 in MSA with the AMULET study, a phase 2 trial to evaluate safety, tolerability, and efficacy in MSA ...

6.

nature.com

nature.com/articles/s41531-024-00849-1

Rational selection of the monoclonal α-synuclein antibody ...

Amlenetug (Lu AF82422) is a human monoclonal antibody targeting α-synuclein in clinical development for multiple system atrophy.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05104476

NCT05104476 | A Study of Lu AF82422 in Participants ...

Study Overview. Brief Summary. To find out the effect of Lu AF82422 on disease progression in participants with multiple system atrophy.

8.

lundbeck.com

lundbeck.com/content/dam/lundbeck-com/masters/global-site/global-site/investors/2024/amulet-update/Lu%20AF82422%20phase%20II%20PoC%20read-out%20(AMULET)_31012024.pdf

Lu AF82422: Potential first disease- modifying therapy in ...

Loss of ambulation, speech, etc. Meaningful reduction in the rate of clinical deterioration. Disease-modifying potential. Potential treatment ...

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34709986/

Nonclinical safety evaluation, pharmacokinetics, and target ...

Here we describe the nonclinical program to support a first-in-human (FIH) single ascending dose (SAD) study for Lu AF82422, a human recombinant, anti-alpha- ...