Verdiperstat for Frontotemporal Dementia

(Veri-T-001 Trial)

Recruiting at 4 trial locations

Overseen By Ian Grant, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Peter Ljubenkov, MD

Must be taking: Alzheimer's medications, Psychotropic medications

Must not be taking: CYP1A2 inhibitors, Corticosteroids

Disqualifiers: Alzheimer's, Autoimmune disease, Cardiovascular, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

64 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the safety of Verdiperstat, a medication taken regularly, in patients with language difficulties caused by brain issues. The study aims to see if the drug can change protein levels in the brain and improve cognitive functions.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications, but certain medications must be stable for a period before starting the trial. Alzheimer's and psychotropic medications need to be stable for 2 months, and other medications for 30 days before the screening visit.

How is the drug Verdiperstat unique for treating frontotemporal dementia?

Verdiperstat is unique because it targets oxidative stress and inflammation in the brain, which are believed to contribute to neurodegeneration in frontotemporal dementia. This mechanism of action is different from other treatments that primarily focus on symptom management rather than addressing underlying disease processes. ^{1 2 3 4 5}

Research Team

Peter Ljubenkov, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults aged 18-85 with semantic variant primary progressive aphasia due to TDP-43 pathology. Participants must be able to swallow pills, have a study partner, and agree to contraception if of childbearing potential. Exclusions include significant cardiovascular, renal or hepatic disease; recent immunosuppressants use; certain blood disorders; uncontrolled thyroid disease; major psychiatric illness; and known sensitivity to Verdiperstat's ingredients.

Inclusion Criteria

Agrees to 2 LPs

I can swallow pills whole without needing to crush or chew them.

My MRI shows svPPA without major strokes or severe brain damage.

Exclusion Criteria

Your blood tests show low neutrophil count, low platelet count, high serum creatinine, high total bilirubin, high alanine aminotransferase, high aspartate aminotransferase, or high international normalized ratio.

Participants who, in the opinion of the PI, are unable or unlikely to comply with the dosing schedule or study evaluations

Your kidney function, as measured by eGFR, is very low, and your serum creatinine or Hemoglobin A1C levels are too high.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Verdiperstat or placebo twice daily for 24 weeks to assess safety, tolerability, and efficacy

24 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Verdiperstat

Trial Overview The Veri-T trial is testing the safety and effectiveness of Verdiperstat taken twice daily by patients with svPPA due to FTLD-TDP. The study will last for 24 weeks where three-fourths of participants receive Verdiperstat and one-fourth receive a placebo.

Participant Groups

Group I: Verdiperstat Experimental Treatment 1 Intervention

Verdiperstat 2 tablets twice daily (600mg total daily) by mouth for 24 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo 2 tablets twice daily by mouth for 24 weeks.

Verdiperstat is already approved in United States, European Union for the following indications:

Approved in United States as Verdiperstat for:

• None approved; under investigation for Multiple System Atrophy (MSA) and semantic variant primary progressive aphasia (svPPA)

Approved in European Union as Verdiperstat for:

• None approved; under investigation for Multiple System Atrophy (MSA)

Who Is Running the Clinical Trial?

Peter Ljubenkov, MD

Lead Sponsor

Trials

1

Recruited

60+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

In a study of 30 patients with behavioral variant frontotemporal dementia (bvFTD) and 131 patients with other dementias, researchers found that high initial scores on behavioral assessments correlated with a decline in symptoms over time, but no specific pattern of symptom change was observed in the sixth year of bvFTD.

The study suggests that educational level may influence the rate of disinhibition symptoms, and that both apathy and disinhibition are likely to decrease as dementia progresses, although longer observation periods may be needed to fully understand these changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trajectories of Behavioural Disturbances Across Dementia Types. Linds, AB., Kirstein, AB., Freedman, M., et al.[2015]

Patients with frontotemporal dementia (FTD) have a significantly shorter survival time (4.2 years) compared to those with Alzheimer disease (AD) (6.0 years), indicating a more aggressive disease progression for FTD.

FTD patients also experience a faster rate of cognitive decline, with an average decrease of 6.7 points on the Mini-Mental State Examination (MMSE) per year, compared to a 2.3 point decline in AD patients, highlighting the urgent need for targeted interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of progression differs in frontotemporal dementia and Alzheimer disease. Rascovsky, K., Salmon, DP., Lipton, AM., et al.[2007]

Caregivers of patients with behavioral variant frontotemporal dementia (bvFTD) experience significantly higher burden compared to those caring for patients with semantic variant primary progressive aphasia (svPPA) and non-fluent variant primary progressive aphasia (nfvPPA), as indicated by higher scores on the Caregiver Strain Index (CSI) and Zarit Burden Interview (ZBI).

Over a follow-up period of up to 2 years, caregiver burden increased in svPPA patients, correlating with factors such as personality changes, neuropsychiatric symptoms, and caregiver age, highlighting the need for ongoing support for caregivers from the time of diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caregiver burden in patients with behavioural variant frontotemporal dementia and non-fluent variant and semantic variant primary progressive aphasia. Guger, M., Raschbacher, S., Kellermair, L., et al.[2022]

In a study of 66 patients with behavioral variant frontotemporal dementia (bvFTD), late-onset patients showed more frequent and severe hippocampal atrophy compared to presenile patients, indicating a distinct pattern of brain changes associated with age.

Despite differences in hippocampal atrophy, the levels of key biomarkers in cerebrospinal fluid and plasma, such as T-tau and neurofilament light chain, were similar between late-onset and presenile bvFTD, suggesting that the overall severity of neurodegeneration may be comparable in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrospinal Fluid and Plasma Biomarkers do not Differ in the Presenile and Late-Onset Behavioral Variants of Frontotemporal Dementia. Marelli, C., Hourregue, C., Gutierrez, LA., et al.[2021]

Sporadic frontotemporal dementia (FTD) patients were found to have lower education levels and a higher prevalence of heart diseases compared to familial FTD patients, indicating that lifestyle factors may influence the disease's development.

Finnish FTD patients exhibited lower rates of hypertension and hypercholesterolemia compared to healthy controls and Alzheimer's disease patients, suggesting that certain cardiovascular risk factors may differ in their association with FTD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modifiable potential risk factors in familial and sporadic frontotemporal dementia. Soppela, H., Katisko, K., Gadola, Y., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Trajectories of Behavioural Disturbances Across Dementia Types. [2015]

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

Rate of progression differs in frontotemporal dementia and Alzheimer disease. [2007]

3. Austria pubmed.ncbi.nlm.nih.gov

Caregiver burden in patients with behavioural variant frontotemporal dementia and non-fluent variant and semantic variant primary progressive aphasia. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Cerebrospinal Fluid and Plasma Biomarkers do not Differ in the Presenile and Late-Onset Behavioral Variants of Frontotemporal Dementia. [2021]

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

Modifiable potential risk factors in familial and sporadic frontotemporal dementia. [2022]