Dementia Frontotemporal
Conditions
Keywords
Frontotemporal Dementia, semantic variant, FTD, sv FTD, PPA, sv PPA
Brief summary
The purpose of this clinical trial is to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), immunogenicity, and efficacy of multiple intravenous administrations of the investigational drug NS101, compared to placebo, in patients with semantic variant primary progressive aphasia (svPPA), a subtype of frontotemporal dementia (FTD)
Interventions
NS101 is anti FAM19A5 antibody expected to play as a synapse organizer and reversing synapse dysfunction in various neurological diseases
Placebo (i.e. fake drug without active pharmaceutical ingredient) of NS101
Sponsors
Asan Medical Center
Gangnam Severance Hospital
Konkuk University Medical Center
Hee-Jin Kim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants diagnosed at screening with mild to moderate frontotemporal dementia, semantic variant (svFTD), defined by a CDR® Plus NACC FTLD Sum of Boxes (SOB) score between 4.5 and 15.5. * Participants confirmed to be amyloid-negative based on Amyloid PET scan or CSF results within the past 36 months. Key
Exclusion criteria
* Participants with other degenerative brain diseases as determined by the investigator * Participants with other neurological disorders and uncontrolled acute disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (Safety and Tolerability) | Every Visit for 12month(48weeks) | To evaluate the safety and tolerability of repeated administration of NS101 compared to placebo in patients with semantic variant primary progressive aphasia (svPPA), a subtype of frontotemporal dementia (FTD). \<primary efficacy endpoint\> The incidence, causality, and severity of adverse events (AEs), serious adverse events (SAEs), adverse drug reactions (ADRs), and serious adverse drug reactions (SADRs) by group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma FAM19A5 Concentration | Every Visit for 12month(48weeks) | To assess the pharmacodynamic (PD) effect of NS101 compared to placebo in patients with svPPA |
| Minimum Plasma Concentration of NS101 (Cmin, Ctrough) | Every Visit for 12month(48weeks) | To evaluate the pharmacokinetics (PK) of repeated administration of NS101 compared to placebo in patients with svPPA |
| Anti-Drug Antibodies (ADA) | Every Visit for 12month(48weeks | To evaluate immunogenicity following repeated administration of NS101 compared to placebo |
| Neutralizing Antibodies (NAbs) | Every Visit for 12month(48weeks) | To evaluate the presence of neutralizing antibodies following repeated administration of NS101 compared to placebo |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Neuropsychological Test Scores (FBI) | Changes from baseline at each assessment time point - Screening, Week 24, Week 36, Week48 | Neuropsychological assessment \- Score on Frontal Behavioral Inventory (FBI) |
| Change From Baseline in Neuropsychological Test Scores (FAB) | Changes from baseline at each assessment time point - Screening, Week 24, Week 36, Week48 | Neuropsychological assessment \- Score on Frontal Assessment Battery (FAB) |
| Change From Baseline in Neuropsychological Test Scores (C-SSRS) | Changes from baseline at each assessment time point - Screening, Week 24, Week 36, Week48 | Neuropsychological assessment \- Score on Columbia-Suicide Severity Rating Scale (C-SSRS) |
| Change from Baseline in Biomarkers | Changes from baseline at each assessment time point • Screening, Week 24, Week 36, Week48 | Biomarkers * Concentration of Neurofilament Light Chain (NfL) \[pg/mL\] * Concentration of Glial Fibrillary Acidic Protein (GFAP) \[pg/mL\] |
| Change from Baseline in Brain MRI | Changes from baseline at each assessment time point • Screening, Week 24, Week 36, Week48 | Neuroimaging \- Brain MRI Measures With Functional MRI (fMRI) |
| Change From Baseline in Neuropsychological Test Scores (BNT/WAB) | Changes from baseline at each assessment time point - Screening, Week 24, Week 36, Week48 | Neuropsychological assessment \- Score on Boston Naming Test (BNT) or Western Aphasia Battery (WAB) |
| Change From Baseline in Neuropsychological Test Scores (ADCS-ADL) | Changes from baseline at each assessment time point - Screening, Week 24, Week 36, Week48 | Neuropsychological assessment \- Score on Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) |
Outcome results
None listed