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

Description

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.

Conditions

Frontotemporal Dementia

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Study Overview

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Study Details

Study overview

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.

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

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

Condition
Frontotemporal Dementia
Intervention / Treatment

-

Contacts and Locations

Philadelphia

Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States, 19104

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * 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
  • * 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
  • * 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.
  • * 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

Ages Eligible for Study

18 Years to 80 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

Denali Therapeutics Inc.,

Amy Berger, MD, STUDY_DIRECTOR, Denali Therapeutics Inc.

Study Record Dates

2025-11