A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia (FTD-GRN)

NCT05262023 · tracked via the Priya Life Science Netherlands tracker

Sponsor

Denali Therapeutics Inc

Phase

Phase 1/2

Started

2022-02-01

Last updated

2026-01-15

Condition(s) studied

Frontotemporal Dementia

Investigational drug(s) / intervention(s)

DNL593Placebo

DNL593: Ascending single doses (for healthy participants) and multiple doses (for participants with FTD)

Placebo: Ascending single doses (for healthy participants) and multiple doses (for participants with FTD)

Study summary

This is a Phase 1/2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of DNL593 in two parts followed by an optional open-label extension (OLE) period.

Part A will evaluate the safety, tolerability, PK, and PD of single doses of DNL593 in healthy male and healthy female participants of nonchildbearing potential. Part B will evaluate the safety, tolerability, PK, and PD of multiple doses of DNL593 in participants with frontotemporal dementia (FTD) over 25 weeks. Part B will be followed by Part C, an optional 18-month OLE period available for all participants who complete Part B.

Eligibility

Sex

ALL

Min age

18 Years

Max age

80 Years

Healthy volunteers

Accepted

Key Inclusion Criteria: Part A: * Women of non-childbearing potential (surgically sterilized or post menopausal) or men, aged ≥18 to ≤ 55 years * BMI of ≥ 18 to ≤ 32 kg/m² * When engaging in sex with a woman of child bearing potential, two forms of birth control are required Part B: * Women of non-childbearing potential (surgically sterilized or post menopausal) or men, aged ≥18 to ≤ 80 years. Women who are of childbearing potential but on highly effective, low user dependent contraceptive methods will be allowed. * BMI of ≥ 18 to ≤ 32 kg/m² * Have a Clinical Dementia Rating® plus National Alzheimer's Coordinating Center frontotemporal lobar degeneration global score ≥ 0.5 * Have confirmed granulin (GRN) mutation via genetic testing or historical records available for review by investigator * When engaging in sex with a woman of child bearing potential, both the male participant and his female partner must use highly effective contraception Part C: * All participants who completed Part B of this trial are eligible for an 18-month OLE if the participant has no unresolved clinically significant TEAEs, where continued dosing may represent a risk to participant safety. Key Exclusion Criteria: * Have any history of clinically significant neurologic, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders * Have a history of malignancy, except fully resected basal cell carcinoma or other malignancies at low risk of recurrence * Have a clinically significant history of stroke, cognitive impairment due to causes other than FTD, seizure within 5 years of screening, or head trauma with loss of consciousness within 2 years of screening * Have a positive serum pregnancy test or are currently lactating or breastfeeding

Primary outcome measure(s)

Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs) — up to 18 months
Incidence of treatment-emergent clinically significant abnormalities in safety laboratory values — up to 18 months
Change from baseline in vital sign measurements: systolic and diastolic blood pressure — up to 18 months
Change from baseline in vital sign measurements: heart rate — up to 18 months
Change from baseline in vital sign measurements: respiratory rate — up to 18 months
Change from baseline in vital sign measurements: body temperature — up to 18 months
Change from baseline in electrocardiogram (ECG) results including PR, QRS, and QTcF intervals — up to 18 months
Incidence of treatment-emergent clinically significant abnormalities in physical/neurological examination findings — up to 18 months
Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS; Parts B and C only) — up to 18 months

Trial sites (26)

Facility	City	Region
University of California San Francisco	San Francisco	California
John Hopkins University	Baltimore	Maryland
Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
University of Antwerp	Antwerp	Belgium
UZ Leuven	Leuven	Belgium
L2IP - Instituto de Pesquisas Clinicas LTDA	Brasília	Brazil
Faculdade de Medicina Da Universidade de São Paulo	São Paulo	Brazil
Hospital Universitario San Ignacio	Bogotá	Colombia
Grupo de Neurosicencias de la Universidad de Antioquia	Medellín	Colombia
Fakultni nemocnice v Motole	Prague	Czechia
CHU de Nantes	Nantes	France
CHU Rouen	Rouen	France
CHU Toulouse	Toulouse	France
ASST degli Spedali Civili di Brescia	Brescia	Italy
Azienda Ospedaliera Universitaria Careggi	Florence	Italy
IRCCS Istituto Auxologico Italiano	Milan	Italy
Azienda Ospedaliera Cardinale G Panico	Tricase	Italy
Erasmus University Medical Center	Rotterdam	Netherlands
Hospital de Braga	Braga	Portugal
Campus Neurológico Sénior	Torres Vedras	Portugal
Hospital Clinic de Barcelona	Barcelona	Barcelona
Hospital Universitario de Donostia	Donostia / San Sebastian	Guipúzcoa
Hospital Universitario Virgen del Rocio	Seville	Sevilla
Istanbul University Istanbul Medical Faculty	Istanbul	Turkey (Türkiye)
Ondokuz Mayis University Hospital	Samsun	Turkey (Türkiye)
Simbec Orion	Merthyr Tydfil	Wales

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A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II) Active, not recruiting

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Other trials for the same condition

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05262023 on ClinicalTrials.gov ↗ ← All trials in the Netherlands