Semantic DementiaPhase 1Veri-T-001NCT05184569
Veri-T: A Trial of Verdiperstat in Patients With svPPA Due to TDP-43 Pathology
A Phase 1 study testing Verdiperstat in people with Semantic Dementia, run by Peter Ljubenkov, MD at 5 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Semantic Dementia
- What is being tested?
- Verdiperstat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 5 sitesUnited States
- Study dates
- 14 Apr 2022to 31 Jan 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- FDA-approved psychotropic medications;
- 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;
- 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.
Who cannot join
- 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);
- progressive supranuclear palsy (PSP; Höglinger et al. 2017); e. corticobasal syndrome (CBS; Armstrong et al. 2013);
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- 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;
- History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof at screening);
- History or presence of gastrointestinal (GI) or other disease known to interfere with absorption, distribution, metabolism, or excretion of drugs, or a history of surgery known to interfere with absorption or excretion of drugs (i.e., gastric bypass);
- Within 1 year prior to initial screening visit or between screening and baseline (pre-dose Day 1), any of the following: myocardial infarction; hospitalization for congestive heart failure; hospitalization for, or symptoms of, unstable angina; or syncope;
- History of major psychiatric illness or untreated depression that in the opinion of the PI would pose a safety risk or interfere with the appropriate interpretation of study data;
- Neutrophil count <1,500/cubic millimeter (mm3), platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin (TBL) >1.5 x ULN, alanine aminotransferase (ALT) >1.5 x ULN, aspartate aminotransferase (AST) >1.5 x ULN, or international normalized ratio (INR) >1.2 at screening (confirmed by repeat);
- Evidence of any clinically significant findings on screening or baseline evaluations which, in the opinion of the PI would pose a safety risk or interfere with appropriate interpretation of study data;
- Corrected QT interval by Fridericia (QTcF) ≥ 470 milliseconds (msec) or uncontrolled arrhythmia or frequent premature ventricular contractions (PVCs; >5/minute) or Mobitz Type II second or third degree atrioventricular (AV) block or left bundle branch block or right bundle branch block with a QRS duration ≥ 150 msec or intraventricular conduction defect with a QRS duration ≥ 150 msec or evidence of acute or sub-acute myocardial infarction or ischemia or other ECG findings at screening or baseline that, in the PI's opinion, would preclude participation in the study;
- Pathologic renal findings at screening as defined by the presence of either of the following criteria:
- Estimated glomerular filtration rate (eGFR) [determined by the Modification of Diet in Renal Disease (MDRD) Study equation] < 30 milliliter (mL)/minute/1.73 square meter (m2). The MDRD Study equation is as follows: eGFR (mL/minute/1.73 m2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American), where Scr = serum creatinine in mg/deciliter (dL) as measured by a method calibrated to an isotope dilution mass spectrometry (IDMS) reference method;
- Serum creatinine ≥ 2.5 mg/dL;
- Hemoglobin A1C >7.5% at screening (confirmed by repeat);
- Current or recent history (within four weeks prior to initial screening visit) of a clinically significant bacterial, fungal, or mycobacterial infection;
- Current clinically significant viral infection, including "known" positive status for human immunodeficiency virus (HIV) (i.e., based on prior testing; HIV testing will not be performed as part of the screening evaluations for this trial);
- Major surgery within four weeks prior to initial screening visit;
- Blood transfusion within 4 weeks of initial screening visit;
- History of stem cell treatment;
- Any contraindication for MRI or unable to tolerate MRI at screening;
- Any contraindication to or unable to tolerate LP at screening, including the use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to the initial screening visit;
- Participants who, in the opinion of the PI, are unable or unlikely to comply with the dosing schedule or study evaluations;
- Prior treatment with verdiperstat;
- Treatment with another investigational drug within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with investigational drugs other than verdiperstat while on study will not be allowed;
- Treatment with systemic corticosteroids or steroid sparing systemic immunosuppressive agents within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with systemic corticosteroids or other systemic immunosuppressive therapy while on study will not be allowed;
- Treatment with strong inhibitors of CYP1A2 (i.e., ciprofloxacin, enoxacin, fluvoxamine) within 30 days or 5 half-lives of drug before initial screening visit, whichever is longer. Treatment with strong inhibitors of CYP1A2 while on study will not be allowed;
- Known hypersensitivity to the inactive ingredients in the study drug products (active or placebo);
- Known to be pregnant or lactating, or positive pregnancy test at screening or baseline (pre-dose Day 1);
- Cancer within 5 years of initial screening visit, except for basal cell carcinoma;
- History or evidence at screening of known disease-associated mutations associated with FTLD without trans-activation response deoxyribonucleic acid-binding protein of 43 kilodaltons (TDP-43) inclusions [e.g., mutations in the genes encoding chromatin-modifying protein/charged multivesicular body protein B2 (CHMPB2), microtubule-associated protein tau (MAPT), or fused in sarcoma (FUS)].
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Northwestern University
Chicago, Illinois, 60611
Houston Methodist Hospital - Nantz National Alzheimer Center
Houston, Texas, 77030
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Rochester, Minnesota, 55905
UCSF Memory and Aging Center
San Francisco, California, 94158
About this study
Official title: Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of Oral Verdiperstat (BHV-3241) in Patients With Semantic Variant Primary Progressive Aphasia (svPPA) Due to TDP-43 Pathology
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.
Read the 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.
- Conditions
- Semantic Dementia
- Being tested
- Verdiperstat
- Medical subject headings
- Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VerdiperstatDrug
Also called BHV-3241
Oral, extended release (ER) tablet
| Study group | Role | What they receive |
|---|---|---|
| Verdiperstat | Experimental | Verdiperstat 2 tablets twice daily (600mg total daily) by mouth for 24 weeks. Receives: Drug: Verdiperstat |
| Placebo | Placebo comparator | Placebo 2 tablets twice daily by mouth for 24 weeks. Receives: Drug: Verdiperstat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Assess adverse events during 6 months administration of Verdiperstat or Placebo
Measured: 24 Weeks
Secondary outcomes (2)
Changes in Pharmacokinetic properties of Verdiperstat in Cerebrospinal Fluid (CSF)
Measure steady-state cerebrospinal fluid concentrations of Verdiperstat and its metabolites
Measured: 24 Weeks
Changes in Pharmacokinetic properties of Verdiperstat in Plasma
Measure steady-state plasma concentrations of Verdiperstat and its metabolites
Measured: 24 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study start14 Apr 2022
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Semantic DementiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Double-Blind, Placebo-Controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peter Ljubenkov, MD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Alzheimer's Association, National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Peter Ljubenkov, MD, University of California, San Francisco
- Investigators
- Peter Ljubenkov, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05184569
- Sponsor's protocol ID
- 21-35516
- Other IDs
- 1R01AG073482-01, PTCG-21-818270
- Acronym
- Veri-T-001
- Status last verified
- Jul 2026
- First submitted
- 17 Dec 2021
- Last updated
- 6 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of Oral Verdiperstat (BHV-3241) in Patients With Semantic Variant Primary Progressive Aphasia (svPPA) Due to TDP-43 Pathology
- ClinicalTrials.gov ID
- NCT05184569
- Acronym / sponsor ID
- Veri-T-001 / 21-35516
- Conditions
- Semantic Dementia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Peter Ljubenkov, MDUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Alzheimer's Association, National Institute on Aging (NIA)
- Study start
- 14 Apr 2022 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 31 Jan 2027 (estimated)
- First posted
- 11 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, Double-Blind, Placebo-Controlled
| Arm | Type | Receives |
|---|---|---|
| Verdiperstat | Experimental | Drug: VerdiperstatVerdiperstat 2 tablets twice daily (600mg total daily) by mouth for 24 weeks. |
| Placebo | Placebo comparator | Drug: VerdiperstatPlacebo 2 tablets twice daily by mouth for 24 weeks. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (36 listed)
- 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:
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VerdiperstatAlso: BHV-3241Oral, extended release (ER) tablet | Drug | Placebo, Verdiperstat |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 24 Weeks
Assess adverse events during 6 months administration of Verdiperstat or Placebo
2 secondary outcomes
Changes in Pharmacokinetic properties of Verdiperstat in Cerebrospinal Fluid (CSF)
Time frame: 24 Weeks
Changes in Pharmacokinetic properties of Verdiperstat in Plasma
Time frame: 24 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Ljubenkov, MD principal investigator
University of California, San Francisco
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Verdiperstat in people with Semantic Dementia, run by Peter Ljubenkov, MD at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: 24 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2026.