TEV-56286 for Multiple System Atrophy

(TOPAS-MSA Trial)

Recruiting at 23 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Disqualifiers: Substance abuse, Pregnancy, Vulnerable populations, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The primary objective of the study is to evaluate the efficacy of TEV-56286 administered orally for the treatment of adult participants with Multiple System Atrophy (MSA). A secondary objective of the study is to evaluate specific efficacy parameters of TEV-56286. Another secondary objective is to evaluate the safety and tolerability of TEV-56286. The planned study period per participant is 56 weeks including a screening period (up to 4 weeks), a 48-week double-blind treatment period, and a follow-up visit (approximately 4 weeks after the end of the double-blind treatment period). The study duration will be approximately 27 months.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but it mentions that using certain prohibited medications is not allowed. It's best to contact the study investigator for more details.

How is the drug TEV-56286 different from other treatments for multiple system atrophy?

TEV-56286 (Emrusolmin, Anle-138b) is unique because it targets the aggregation of alpha-synuclein, a protein that builds up in the brains of people with multiple system atrophy, which is a novel approach compared to existing treatments that mainly focus on symptom management. ^{1 2 3 4 5}

Research Team

Tev Medical Expert, Study Director

Principal Investigator

Teva Branded Pharmaceutical Products R&D, Inc.

Eligibility Criteria

This trial is for adults with Multiple System Atrophy (MSA), a progressive neurological disorder. Participants must be able to take oral medication and commit to the study duration of about 56 weeks, including follow-up.

Inclusion Criteria

I am a man who can father children and will use effective birth control.

Patient is considered to be 'clinically possible' or 'clinically probable' MSA as determined by the Gilman criteria

I can walk 10 meters on my own, but I may use a cane.

Exclusion Criteria

Patient has a known hypersensitivity to any components of the IMP

Patient has a history of, or acknowledges, alcohol or other substance abuse in the 12 months before screening

Patient has participated in another clinical study involving administration of an IMP within 3 months or 5 half-lives (whichever is longer) of this IMP prior to screening

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive TEV-56286 or placebo orally once daily during the double-blind treatment period

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TEV-56286 (Other)

Trial Overview The trial is testing TEV-56286's effectiveness in relieving symptoms of MSA compared to a placebo. It involves taking the drug orally over a period of 48 weeks, with specific efficacy parameters being evaluated alongside safety and tolerability.

Participant Groups

Group I: TEV-56286 Experimental Treatment 1 Intervention

Orally administered capsules once daily

Group II: Placebo Placebo Group 1 Intervention

Orally administered capsules once daily

Who Is Running the Clinical Trial?

Teva Branded Pharmaceutical Products R&D, Inc.

Lead Sponsor

Trials

258

Recruited

3,487,000+

Dr. Eric Hughes

Teva Branded Pharmaceutical Products R&D, Inc.

Chief Medical Officer since 2022

MD and PhD from Yale School of Medicine

Richard Francis

Teva Branded Pharmaceutical Products R&D, Inc.

Chief Executive Officer since 2022

Bachelor's degree in Biochemistry from the University of Manchester

Findings from Research

In a preliminary study of 20 patients with multiple system atrophy and predominant cerebellar ataxia, intravenous amantadine treatment significantly reduced ataxia severity, with scores improving from 42.5 to 37.3 (p < 0.001).

All subjects reported subjective improvement after treatment, and no side effects were observed, suggesting that intravenous amantadine may be a safe management option, although further research is needed to understand its mechanism and confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary study of intravenous amantadine treatment for ataxia management in patients with probable multiple system atrophy with predominant cerebellar ataxia. Youn, J., Shin, H., Kim, JS., et al.[2021]

In a study of 14 patients with multiple system atrophy parkinsonism (MSA-P), high-dose intravenous amantadine for 5 days led to clinical improvement in 71.4% of subjects, with a significant decrease in disease severity as measured by the Unified Multiple System Atrophy Rating Scale (UMSARS).

The treatment was generally safe, with only mild and transient adverse effects reported, although one patient experienced acute psychosis, which resolved after stopping the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Parenteral Amantadine Therapy in the Treatment of Multiple System Atrophy With Predominant Parkinsonism. Friedberg, A., Erikh, I., Nassar, M., et al.[2018]

In a study involving PLP-α-syn transgenic mice, treatment with ATH434 for 6 months preserved motor performance and protected against neuron loss, indicating its potential as a disease-modifying therapy for multiple system atrophy (MSA).

ATH434 treatment led to a significant reduction in α-synuclein aggregates and oligomers, increased microglial lysosomal activity, and lower iron levels in the substantia nigra, suggesting a mechanism of action that enhances α-syn clearance without increasing inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ATH434 Reduces α-Synuclein-Related Neurodegeneration in a Murine Model of Multiple System Atrophy. Heras-Garvin, A., Refolo, V., Schmidt, C., et al.[2022]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Preliminary study of intravenous amantadine treatment for ataxia management in patients with probable multiple system atrophy with predominant cerebellar ataxia. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Multiple system atrophy: an update. [2013]

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

Efficacy of Parenteral Amantadine Therapy in the Treatment of Multiple System Atrophy With Predominant Parkinsonism. [2018]

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

ATH434 Reduces α-Synuclein-Related Neurodegeneration in a Murine Model of Multiple System Atrophy. [2022]