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

 Frontotemporal Dementia / Posted 2 months ago

Brief 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.

  • 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, both the male participant and his female partner must use highly effective contraception
    • 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.
  • 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
  • Study end date : November 2025
  • Wales-Based Study Contact : Annelize Koch, MD
  • Principal Investigator : Annelize Koch, MD
Contact details

Simbec-Orion Group Ltd, Simbec House, Merthyr Tydfil Industrial Park,Merthyr Tydfil,CF48 4DR  Show Phone Number Enrolmentservices@simbecorion.com www.simbecorion.com

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