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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether the drug Verdiperstat (also known as AZD3241 or BHV-3241) is safe and tolerable for individuals with semantic variant primary progressive aphasia (svPPA), a type of dementia affecting language skills. Participants will receive either Verdiperstat or a placebo (a harmless pill with no active drug) for 24 weeks. The trial seeks individuals diagnosed with svPPA and brain scan results consistent with the condition. Those who have svPPA and can swallow pills without crushing them may be suitable for the trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

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

Research has shown that Verdiperstat is under study to assess its safety and tolerability. As this is an early trial, limited safety information is available. However, testing Verdiperstat in humans suggests that earlier studies, likely in animals, indicated it might be safe enough for human trials.

In the trial, three out of four participants will take Verdiperstat, while one out of four will take a placebo (a pill with no active medicine). This design helps scientists determine if Verdiperstat causes any side effects or issues compared to taking nothing.

For those considering participation, note that this trial is an initial evaluation of how people respond to Verdiperstat. By participating, individuals contribute to researchers' understanding of its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for frontotemporal dementia focus on managing symptoms, but Verdiperstat works differently by targeting the enzyme myeloperoxidase. This enzyme is involved in inflammation and oxidative stress, which are believed to contribute to the progression of the disease. By inhibiting myeloperoxidase, Verdiperstat aims to slow down or alter the disease process itself, offering hope for a more effective approach to treating this challenging condition. Researchers are particularly excited about this potential because it represents a shift from symptom management to addressing the underlying disease mechanisms.

What evidence suggests that Verdiperstat might be an effective treatment for frontotemporal dementia?

Research suggests that Verdiperstat, which participants in this trial may receive, may help with conditions like frontotemporal dementia. In studies with patients who had multiple system atrophy, Verdiperstat was tested against a placebo and showed potential in easing symptoms. Verdiperstat reduces inflammation in the brain, which might help slow the damage caused by brain diseases. Although specific data on frontotemporal dementia is limited, Verdiperstat's mechanism suggests it could be helpful. Early signs are promising, but more research is needed to fully understand its effects on frontotemporal dementia. ^{1 2 4 6 7}

Who Is on the Research Team?

Peter Ljubenkov, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05184569

Veri-T: A Trial of Verdiperstat in Patients With svPPA Due ... The purpose of the study is to test the safety and tolerability of twice daily Verdiperstat in patients with semantic variant primary progressive aphasia ...

2. reporter.nih.gov reporter.nih.gov/search/t_kbDTVMR0KOnhtdmsXJ0w/project-details/10893644

Veri-T: A phase 1 Placebo-Controlled Trial of Verdiperstat in ... Our proposed discovery and longitudinal characterization of candidate measures of svPPA biological and clinical severity will provide essential information, ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20471965

A Study of BHV-3241 in Subjects with Multiple System ... The purpose of this study is to compare the effectiveness of BHV-3241 versus placebo in subjects with Multiple System Atrophy. Participation eligibility.

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.067255

Introduction to Veri‐T: A Phase 1 Randomized, Double‐Blind ... The Veri-T trial examines the safety, tolerability and pharmacokinetic properties of verdiperstat in svPPA, and explores novel pharmacodynamic biomarkers and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9044101/

Comprehensive cross-sectional and longitudinal analyses ... Frontotemporal dementia (FTD) therapy development is hamstrung by a lack of susceptibility, diagnostic, and prognostic biomarkers.

6. boxerlab.ucsf.edu boxerlab.ucsf.edu/clinical-trial/phase-1-randomized-double-blind-placebo-controlled-safety-tolerability

Phase 1, Randomized, Double-Blind, Placebo ... - Boxer Lab The purpose of the study is to test the safety and tolerability of twice-daily Verdiperstat in patients with semantic variant primary progressive aphasia (svPPA) ...

7. ftdregistry.org ftdregistry.org/press/featured-study-veri-t/

Featured Study: Veri-T The purpose of the study is to test the safety and tolerability of twice-daily Verdiperstat in patients with semantic variant primary progressive aphasia (svPPA) ...