Semantic Dementia
Conditions
Brief summary
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) due to frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Three-fourths of the participants will receive Verdiperstat and one-fourth will receive Placebo during the 24-week treatment duration.
Detailed description
This is a Phase 1, randomized, double-blind, placebo-controlled study of the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Verdiperstat in patients with semantic variant primary progressive aphasia (svPPA) due to frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Approximately 64 subjects will be randomized 3:1 to active drug or placebo. Study drug will be administered orally bid (two Verdiperstat tablets bid or two placebo tablets bid (for a total daily dose of 600mg daily, following a one-week titration period of 1 tablet daily). The study will test the effects of Verdiperstat on cerebrospinal fluid (CSF) proteins, brain magnetic resonance imaging (MRI), and cognitive (thinking, memory and language) tests in subjects with svPPA due to FTLD-TDP. This study uses placebo which looks like the experimental drug but does not have any active drug in it.
Interventions
DRUGVerdiperstat
Oral, extended release (ER) tablet
Sponsors
National Institutes of Health (NIH)
Alzheimer's Association
National Institute on Aging (NIA)
Peter Ljubenkov, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind study. Only investigational pharmacist will be unblinded
Intervention model description
Randomized, Double-Blind, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Between 18 and 85 years of age (inclusive) at the initial screening visit; 2. Meets 2011 consensus criteria for svPPA (Gorno-Tempini et al. 2011); 3. MRI at screening is consistent with the underlying svPPA with no large strokes or severe white matter disease (Fazekas Grade ≤2; Fazekas et al. 1987); 4. CDR® plus NACC FTLD (Miyagawa et al. 2020) global score at screening ≤1; 5. The following medications are allowed, but must be stable for 2 months prior to the initial screening visit: 1. Food and Drug Administration (FDA)-approved Alzheimer's disease (AD) medications; 2. FDA-approved psychotropic medications; 6. Other medications (except those listed under
Exclusion criteria
) are allowed as long as the dose is stable for 30 days prior to the initial screening visit; 7. Has a reliable study partner who agrees to accompany the participant to visits, and spends at least 5 hours per week with the participant; 8. Agrees to 2 LPs; 9. Signed and dated written informed consent obtained from the participant and the participant's study partner in accordance with local Institutional Review Board (IRB) regulations; 10. WOCBP must agree to abstain from sex or use highly effective birth control that includes two methods of contraception (one of which must be a barrier method) for the duration of the screening period, the RDBPC treatment period, and for 30 days after the last dose of study drug (active or placebo); 11. Males must agree to abstain from sex with WOCBP or use an adequate method of contraception for the duration of the RDBPC treatment period and for 90 days after the last dose of study drug (active or placebo); 12. Able to swallow pills whole without crushing or chewing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 24 Weeks | Assess adverse events during 6 months administration of Verdiperstat or Placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Pharmacokinetic properties of Verdiperstat in Cerebrospinal Fluid (CSF) | 24 Weeks | Measure steady-state cerebrospinal fluid concentrations of Verdiperstat and its metabolites |
| Changes in Pharmacokinetic properties of Verdiperstat in Plasma | 24 Weeks | Measure steady-state plasma concentrations of Verdiperstat and its metabolites |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in structural and functional connectivity on brain MRI | 24 Weeks | Connectivity between brain regions measured using diffusion tensor MRI and resting state functional MRI |
| Change in Clinical Dementia Rating Scale (CDR-SB) | 24 Weeks | Measure change in dementia status using the Clinical Dementia Rating (CDR) Demential Staging Instrument plus National Alzheimer's Coordinating Center (NACC) Behavior and Language Domains (CDR plus NACC FTLD) |
| Change in Executive brain function | 24 Weeks | Measure change in executive function using the National Institutes of Health (NIH) Executive Abilities Assessment (NIH EXAMINER) |
| Changes in Pharmacodynamic (PD) properties of Verdiperstat in Plasma | 24 Weeks | Measure plasma myeloperoxidase (MPO) activity |
| Change in language semantic fluency | 24 Weeks | Measure semantic fluency using the Delis-Kaplan Executive Function System (D-KEFS) |
| Change in language naming function | 24 Weeks | Measure language function abilities using a digitalized analysis of prompted monolog and a picture description task on a mobile application |
| Change in neuropsychiatric function | 24 Weeks | Measure using the Neuropsychiatric Inventory (NPI) questionnaire |
| Change in language function | 24 Weeks | Measure change in language function using the Boston Naming Test |
| Changes in Pharmacodynamic properties of CSF biomarkers of neurofilament light chain protein | 24 Weeks | Measure CSF concentrations of neurofilament light chain protein (NfL) pg/ml |
| Change in brain volume on brain MRI | 24 Weeks | Measure of global and regional volumes of interest (such as whole brain and temporal lobes) |
Countries
United States
Contacts
Primary ContactKarin Snowberg, MA
Backup ContactWhitney Walker, MS, CNS, RN
Outcome results
None listed