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

Launched by DENALI THERAPEUTICS INC. · Feb 26, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called DNL593 to see how safe it is and how well it works for people, focusing on those with Frontotemporal Dementia (FTD). The trial is divided into three parts: the first part involves healthy adults, and the second part includes adults aged 18 to 80 who have been diagnosed with FTD. Participants will take either a single dose or multiple doses of DNL593 over several weeks, and there will be a follow-up period for those who complete the second part.

To be eligible, healthy participants need to be between 18 and 55 years old, while those with FTD can be between 18 and 80 years old, but they must have specific genetic changes related to the disease. Participants should not have serious health conditions such as major illnesses or recent significant medical events. This trial aims to gather important information about how DNL593 affects the body and to ensure it is safe for people with FTD. If you join the trial, you’ll have the opportunity to contribute to research that could help others with this condition.

Gender

ALL

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