Veri-T: A Trial of Verdiperstat in Patients With svPPA Due to TDP-43 Pathology

NCT05184569 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: 21-355161R01AG073482-01PTCG-21-818270
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 5

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.

Conditions

Semantic Dementia

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Assess adverse events during 6 months administration of Verdiperstat or Placebo

  24 Weeks

Secondary Outcomes (2)

• Changes in Pharmacokinetic properties of Verdiperstat in Cerebrospinal Fluid (CSF)

  24 Weeks

• Changes in Pharmacokinetic properties of Verdiperstat in Plasma

  24 Weeks

Other Outcomes (10)

• Changes in Pharmacodynamic (PD) properties of Verdiperstat in Plasma

  24 Weeks

• Changes in Pharmacodynamic properties of CSF biomarkers of neurofilament light chain protein

  24 Weeks

• Change in brain volume on brain MRI

  24 Weeks

Study Arms (2)

Verdiperstat

EXPERIMENTAL

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

Drug: Verdiperstat

Placebo

PLACEBO COMPARATOR

Placebo 2 tablets twice daily by mouth for 24 weeks.

Drug: Verdiperstat

Interventions

Verdiperstat DRUG

Oral, extended release (ER) tablet

Also known as: BHV-3241

Placebo; Verdiperstat

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 18 and 85 years of age (inclusive) at the initial screening visit;
• Meets 2011 consensus criteria for svPPA (Gorno-Tempini et al. 2011);
• 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);
• CDR® plus NACC FTLD (Miyagawa et al. 2020) global score at screening ≤1;
• The following medications are allowed, but must be stable for 2 months prior to the initial screening visit:
• Food and Drug Administration (FDA)-approved Alzheimer's disease (AD) medications;
• FDA-approved psychotropic medications;

You may not qualify if:

• Has a reliable study partner who agrees to accompany the participant to visits, and spends at least 5 hours per week with the participant;
• Agrees to 2 LPs;
• 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;
• 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);
• 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);
• Able to swallow pills whole without crushing or chewing.
• A clinical diagnosis of probable AD (McKhann et al. 2011) or previous biomarker evidence of AD biology using amyloid positron emission tomography (PET) imaging, CSF amyloid beta (Aβ)/total tau (t-tau) ratio, CSF/plasma amyloid beta isoform with 40 amino acid residues (Aβ40)/amyloid beta isoform with 42 amino acid residues (Aβ42) ratio, or plasma phosphorylated tau \[phosphorylated tau at residue 181 (p-tau181) and phosphorylated tau at residue 217 (p-tau217)\] assessments;
• A clinical diagnosis of a comorbid FTLD-associated clinical syndrome other than svPPA, including:
• logopenic primary progressive aphasia (lvPPA; Gorno-Tempini et al. 2011);
• non-fluent/agrammatic variant primary progressive aphasia (nfvPPA; Gorno-Tempini et al. 2011);
• c. behavioral variant for frontotemporal dementia (bvFTD; Rascovsky et al. 2011). Patients who meet diagnostic criteria for svPPA (Gorno-Tempini et al. 2011) may still be included if they have a secondary diagnosis of bvFTD, so long as the PI can reasonably attribute their disinhibition, dietary changes, compulsions, and/or loss of empathy to anterior temporal lobe atrophy (Seeley et al. 2005) and MRI is consistent with right anterior atrophy (or left temporal atrophy in participants with suspected right hemispheric language dominance);
• d. progressive supranuclear palsy (PSP; Höglinger et al. 2017); e. corticobasal syndrome (CBS; Armstrong et al. 2013);
• Any other medical condition other than FTLD that is likely to account for cognitive or behavioral deficits (e.g., uncontrolled seizure disorder, stroke, vascular dementia, substance abuse or alcoholism, Lewy body disease);
• History of uncontrolled thyroid disease or evidence thereof \[i.e., abnormal free thyroxine (T4) levels and thyroid stimulating hormone (TSH) \> 10 milli-international units (mIU)/liter (L) at screening (confirmed by repeat)\];
• Serious autoimmune disease, or ongoing immunocompromised state;

Sponsors & Collaborators

• Peter Ljubenkov, MD: lead
• National Institutes of Health (NIH): collaborator
• Alzheimer's Association: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (5)

UCSF Memory and Aging Center

San Francisco, California, 94158, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Houston Methodist Hospital - Nantz National Alzheimer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Peter Ljubenkov, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karin Snowberg, MA

CONTACT

415-476-8845; Karin.Snowberg@ucsf.edu

Whitney Walker, MS, CNS, RN

CONTACT

415-353-7532; Whitney.Walker@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind study. Only investigational pharmacist will be unblinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Adjunct Professor

Model Details: Randomized, Double-Blind, Placebo-Controlled

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: January 11, 2022
• Study Start: April 14, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: October 15, 2025

Record last verified: 2025-10

Locations

US (5)