Evaluating DNL593 for Frontotemporal Dementia

A Phase 1/2, Multicenter, Randomized, Placebo-Controlled, Double Blind Single Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia Followed by an Open-Label Extension

This study is testing a new drug called DNL593 to see if it is safe and helpful for people with frontotemporal dementia.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 106 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Denali Therapeutics Inc. (industry)
• Locations: 29 sites (Philadelphia, Pennsylvania and 28 other locations)
• Trial ID: NCT05262023 on ClinicalTrials.gov

What this trial studies

This is a Phase 1/2, multicenter, randomized, placebo-controlled, double-blind evaluation of DNL593, focusing on its safety, tolerability, pharmacokinetics, and pharmacodynamics. The study consists of two main parts: Part A assesses single doses in healthy participants, while Part B examines multiple doses in individuals with frontotemporal dementia over 25 weeks. An optional open-label extension period follows for participants who complete Part B, allowing for further assessment of the drug's effects.

Who should consider this trial

Good fit: Ideal candidates include men and women aged 18 to 80 with frontotemporal dementia and confirmed granulin mutations.

Not a fit: Patients without a confirmed granulin mutation or those with other forms of dementia may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with frontotemporal dementia.

How similar studies have performed: Other studies targeting frontotemporal dementia have shown promise, but the specific approach of DNL593 is novel.

Eligibility criteria

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

Where this trial is running

Philadelphia, Pennsylvania and 28 other locations

• Hospital of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (RECRUITING)
• University of Antwerp — Antwerp, Belgium (RECRUITING)
• UZ Leuven — Leuven, Belgium (NOT_YET_RECRUITING)
• L2IP - Instituto de Pesquisas Clinicas LTDA — Brasília, Brazil (NOT_YET_RECRUITING)
• Hospital de Clinicas de Porto Alegre (HCPA) - PPDS — Porto Alegre, Brazil (RECRUITING)
• Faculdade de Medicina Da Universidade de São Paulo — São Paulo, Brazil (NOT_YET_RECRUITING)
• Hospital Universitario San Ignacio — Bogotá, Colombia (NOT_YET_RECRUITING)
• Fakultni nemocnice v Motole — Prague, Czechia (WITHDRAWN)
• CHU de Nantes — Nantes, France (RECRUITING)
• CHU Rouen — Rouen, France (RECRUITING)
• CHU Toulouse — Toulouse, France (RECRUITING)
• ASST degli Spedali Civili di Brescia — Brescia, Italy (NOT_YET_RECRUITING)
• Azienda Ospedaliera Universitaria Careggi — Firenze, Italy (RECRUITING)
• IRCCS Istituto Auxologico Italiano — Milano, Italy (RECRUITING)
• Azienda Ospedaliera Cardinale G Panico — Tricase, Italy (NOT_YET_RECRUITING)
• Erasmus University Medical Center — Rotterdam, Netherlands (RECRUITING)
• Hospital de Braga — Braga, Portugal (RECRUITING)
• Hospital Pedro Hispano — Matosinhos, Portugal (NOT_YET_RECRUITING)
• Campus Neurológico Sénior — Torres Vedras, Portugal (NOT_YET_RECRUITING)
• University Clinical Center Nis — Niš, Serbia (NOT_YET_RECRUITING)
• Hospital Universitario de Donostia — Donostia-San Sebastian, Guipúzcoa, Spain (RECRUITING)
• Hospital Clinic de Barcelona — Barcelona, Spain (NOT_YET_RECRUITING)
• Hospital Universitario La Paz — Madrid, Spain (WITHDRAWN)
• Hospital Universitario Virgen del Rocio — Sevilla, Spain (RECRUITING)
• Hacettepe University — Ankara, Turkey (NOT_YET_RECRUITING)
• Istanbul University Istanbul Medical Faculty — Istanbul, Turkey (RECRUITING)
• Dokuz Eylul University Medical Faculty — İzmir, Turkey (NOT_YET_RECRUITING)
• Ondokuz Mayis University Hospital — Samsun, Turkey (RECRUITING)
• Simbec Orion — Merthyr Tydfil, Wales, United Kingdom (COMPLETED)

Study contacts

• Study coordinator: Clinical Trials at Denali Therapeutics

Conditions: Frontotemporal Dementia, FTD, FTD-GRN, granulin