Study to Evaluate DNL747 in Subjects With Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL747 in Subjects With Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03757325
• Other study ID #: DNLI-D-0002
• Status: Completed
• Phase: Phase 1
• Start date: February 13, 2019
• Est. completion date: December 5, 2019

Study information

• Verified date: February 2020
• Source: Denali Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL747 in subjects with Alzheimer's disease when administered for 29 days in a cross-over design

Description:

This is a Phase 1b randomized, placebo-controlled, double-blind, crossover study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL747 in subjects with Alzheimer's disease (AD)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 5, 2019
• Est. primary completion date: December 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Key Inclusion Criteria:

• Women of non-childbearing potential and men, aged 55-85 years

• AD diagnosis based on the 2011 National Institute on Aging-Alzheimer's Association Guidelines

• Supportive evidence for diagnosis of AD based upon positive CSF Aß42 test, or documented history of positive amyloid-specific PET scan

• Screening MMSE score of 16-26 points

• Screening CDR Global Score of 0.5-1.0

• Availability of a person ("caregiver") who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits that require input for scale completion, assists the participant with compliance for at-home study treatment administration, and signs the necessary consent form (note: the caregiver is not required to stay in the unit)

• Approved AD treatments (acetylcholinesterase inhibitors ± memantine) and other prescription medications must be stable for =1 month prior to screening and anticipated to be stable over the duration of the study

Key Exclusion Criteria:

• Clinical history within 2 years of the screening visit or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition

• Magnetic resonance imaging (MRI) at screening (or within 1 year of screening visit) consistent with any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• DNL747
DNL747
• Placebo
Placebo

Locations

Country	Name	City	State
Netherlands	Clinical Site(s)	Groningen
United States	Clinical Site(s)	Dallas	Texas
United States	Clinical Site(s)	Miami	Florida
United States	Clinical Site(s)	Orlando	Florida
United States	Clinical Site(s)	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Denali Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		Randomization - Day 86
Primary	Number of Subjects with clinically significant neurological examination abnormalities		Randomization - Day 86
Primary	Number of Subjects with laboratory test abnormalities		Randomization - Day 86
Secondary	Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747		Randomization - Day 86
Secondary	Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747		Randomization - Day 86
Secondary	Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747		Randomization - Day 86
Secondary	Pharmacokinetic terminal disposition rate constant (?z) with the respective t1/2 of DNL747		Randomization - Day 86
Secondary	Pharmacokinetic measure of CSF concentrations of DNL747		Randomization - Day 86
Secondary	Pharmacodynamic measure of pS166 in PBMCs		Randomization - Day 86