ACTIVE_NOT_RECRUITING

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

Conditions

Frontotemporal Dementia FTD FTD-GRN granulin

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2022-02-01

Study Completion:2028-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05262023

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.

Ages Eligible for Study:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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

Inclusion Criteria

Exclusion 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

Contacts and Locations

Principal Investigator

Amy Berger, MD

STUDY_DIRECTOR

Denali Therapeutics Inc.

Study Locations (Sites)

University of California San Francisco

San Francisco, California, 94143

United States

John Hopkins University

Baltimore, Maryland, 21218

United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: Denali Therapeutics Inc.

Amy Berger, MD, STUDY_DIRECTOR, Denali Therapeutics Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-02-01

Study Completion Date2028-11

Study Record Updates

Study Start Date2022-02-01

Study Completion Date2028-11

Terms related to this study

Keywords Provided by Researchers

FTD
FTD-GRN
granulin

Additional Relevant MeSH Terms

Frontotemporal Dementia